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P1 - Descriptors
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302 Research Design: Types of variables- Eso Okosun
The types of variables are nominal, ordinal, discrete and continuous.
The nominal variable is the simplest form of measurement. It is verbal in nature
rather than numerical. It involves placing experimental unit in categories that are
qualitatively different. The statistics used for nominal variable is called the percentage.
The ordinal variable is a level of measurement that yields rank order of a variable
along some dimension. The transitivity postulate states that if A>B and B>C, then A>C.
The statistics used for ordinal variable is called the median.
The discrete variable is a measurement of the exact quantity of a characteristic
where the quantity can take on certain numeric numbers usually a whole number. The
statistics used here is the mean (average)
The continuous variable is the measurement of the exact quantity of a
characteristic where the quantity can take on any value. The statistics used here is the
mean. The assumption is that no two experimental units can have exactly the same
response. E.g. height, weight, intelligence and temperature.
Interval data: Equal intervals e.g. intelligence
Ratio: equal intervals and a true zero point e.g. length, weight and pulse rate.
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302 Research Design: Study designs Eso Okosun
(R) Randomization (E) Experimental group (C) Control group (Y1) Pre-test (X)
Treatment (Y2) Post test
Pre-experimental designs: In this design, there is no randomization or true control.
Without randomization and control a researcher cannot establish causality.
a. One-shot case study: there is only one group which is the experimental group
E
X Y2
b. One group pre- test, post test
E Y1 X Y2
The Y1 helps to establish the order of occurrence
c. Two groups static
E X Y2
C
Y2
The researcher cannot say the control group is equivalent to the experimental group.
Therefore, the fact that a control group is present is meaningless
Experimental designs
Two groups, Randomized subject, post-test only
(R) E X Y2
(R) C
Y2
The researcher can establish causality
Randomized group, pre-test, post test
(R) E Y1 X Y2
(R) C Y1 Y2
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302 Research Design: Features of study designs Eso Okosun
The features of the various study designs have been explained in the previous question.
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302 Research Design: Sample selection Eso Okosun
There are four ways to select a sample when we want to conduct a research and they
include:
a. Simple random sampling
b. Stratified random sampling
c. Cluster sampling
d. Systematic sampling
In simple random sampling, a u-sample of size n is drawn from a universe of size N in
such a way that every possible u-sample of size n has the same chance of being
selected. The steps in achieving this are as follows:
1.
Number the experimental units in the universe
2.
Go to a random number table
3.
Pick any starting point in the table
4.
Move through the table in any pattern
In Stratified random sampling we select a proportionate share of experimental units
from each level of the extraneous factor called a stratum.
Cluster sampling is a sampling strategy where large groupings (clusters) are selected
first with successive sampling of smaller units.
Systematic sampling is used when a complete list of experimental units in the universe
is available. It involves the calculation of k representing the increment in which the
experimental unit should be chosen from the list.
K= Universe size/Desired u-sample size
For example, if our universe size is 500 and our desired u-sample size is 50 then our k
value will be 10.
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302 Biostatistics: Hypothesis Testing Eso Okosun
Steps in performing research
State the null hypothesis, state the alternative hypothesis, state the significance level,
collect data, calculate “test” statistics, Accept or reject null hypothesis and make
conclusions.
Null hypothesis: A statement of no difference. Symbol is H0
Alternative hypothesis: If null hypothesis is rejected or not true, the alternative
hypothesis will be accepted. The symbol is H1
Significance level: Tradition, convention and custom to set at 0.05. It may be set lower
e.g. 0.01
Collect data e.g. nominal, ordinal, interval and ratio
Calculate “test” statistics: It tests the null hypothesis to determine whether to accept or
reject
P<0.05 reject H0
P>0.05 accept H0 i.e. not conclude there is a difference
Make conclusion
Accept Ho
Reject Ho
No difference
Difference
Groups equal
Groups not equal
Difference not “significant”
Difference significant
Statistically different
Type 1 error: The symbol is α. Rejecting a null hypothesis that is really true, concluding
there is a difference when there is really not and it is quantified by p value.
Type II error: The symbol is β. Accepting a null hypothesis that is really false or
concluding there is no difference when there really is.
Power: The ability to detect a false null hypothesis or ability to detect a difference if one
exists.
Power= 1- β
The larger the β, the larger the probability of committing a type II error and the smaller
the power. The greater the power the better and the average power is 0.8. The factors
that influence power include small size which equals lower power, variability of groups
(the larger the variability of the two groups the smaller the power) and the size of
difference want to detect
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302 Biostatistics: Correlation Eso Okosun
This is the relationship between two or more variables. The statistics commonly used is
the Pearson r. An example might be the relationship that exists between the height and
weight of a group of individuals or the age and cholesterol levels of a group of
individuals.
Pearson r
Relationship between two or more variables
It is continuous and normally distributed
It has a linear relationship
To determine if a relationship is linear, a scattered diagram should be constructed. The
Pearson r is calculated from a formula and the coefficient varies from -1.00 to +1.00.
The calculated value of the Pearson r indicates two things: the direction and magnitude
of the relationship between the two variables. The two variables are usually represented
by X and Y. The X is the independent variable (Dose) and the Y is the dependent
variable (Blood level)
The closer the Pearson r is to -1.00 or +1.00 the greater is the magnitude of the
relationship. The closer the points fall along straight line, closer r is to +1 or -1 and the
more distributed away from straight line, closer r is to 0.
Ho: R=0
R is correlation in population
P=0.07716
Calculated r=+0.5826
Conclusion: Accept Ho, No correlation
The other three correlation used here includes:
a. Spearman (Data ranked)
b. Phi: (fourfold) coefficient (Both variables dichotomous)
c. Point Biserial (One variable continuous, the other Dichotomous)
Multiple correlation: Determines relationship between several variables at once on
one variable. An example is the relationship between the age, weight, sex and dose of
drug on blood level.
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302 Biostatistics: t-tests Eso Okosun
Testing difference in two means. A parametric statistic. Continuous data and normally
distributed are requirement of the t test.
Ho=m1=m2
H1:m1≠m2
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302 Biostatistics: ANOVA Eso Okosun
Analysis of variance. It is a parametric statistic. It tests difference in two or more means.
F=t2 ( 2 groups) SS= sums of squares. A measure of variability. It is a continuous data
and normally distributed.
Degrees of freedom
Between K-1
Within K (N-1)
Total KN-1
MS is mean square
Obtained by dividing SS by DF
F= MS Between/MS within
If P≥0.05, Accept Ho: Analysis is complete
If P<0.05, reject Ho: Post Hoc test
If P<0.05 at least one different
Multi-factor ANOVA allows analysis of interaction of factors.
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302 Biostatistics: Averages Eso Okosun
A number that represents a large number of subjects.
a. Mean: Arithmetic average, the symbol is X bar, X by itself is a symbol for datum or
data.
X bar= eX/n where e is the sum of x
Mi (midpoint of the arbitrary reference)
b. Median: Point or measure in distribution where 50% subjects are above and 50%
subjects below
c. Mode: For a raw data, it is the datum that occurs most frequently. For a group data
it is the mid-point of the interval with the greatest frequency e.g. for a class interval size
of 14.5-14.9 which has a high frequency of 20 the mode will be 14.7
If the data are normal, averages will be similar but if the data are skewed, averages will
be different.
Positive skewed
Mode: Always at the peek
Median
Mean: Pulled to the right
The median is the appropriate average for skewed data while the mean and the mode
is the appropriate average for normal data.
Negatively skewed
Mode: Always at the peek
Median
Mean: pulled to the left
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302 Biostatistics: Variability Eso Okosun
Q( Quartile deviation)
R( Range)= highest measure-lowest measure
AD( Average deviation)
SD ( Standard deviation) = it is used when the distribution is normal
Variance
SEM ( Standard error of the mean)
Quartiles
Q1=C25, Q2=C50, Q3=C75
Q is a statistics of choice for skewed data
Q=Q3-Q1/2
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302 Biostatistics: Evidence Based Medicine Eso Okosun
The conscientious, explicit and judicious use of current best evidence in making
decisions about the care of the individual patient. It means integrating individual clinical
expertise with the best available external clinical evidence from systematic research. It
begins and ends with the patient in mind.
Steps in the process
Identify a patient, formulate an appropriate clinical question, conduct a literature search,
select the key articles, critically appraise the articles and apply the results of the search
to your patient.
Assess, ask, acquire, appraise and apply
Types of questions asked include diagnosis, therapy, prognosis and etiology.
Levels
Primary: Original research. This is the most current source
Secondary: Compilation and interpretation of original research. It summarizes the
primary evidence.
Tertiary: Recommendations regarding clinical applications of secondary evidence.
The case report is the weakest while Randomized controlled trial (RCT) is the
strongest of the primary evidence
Secondary: meta-analysis, systematic review and opinion of respected authorities
Tertiary
Level A: Strong recommendation, Level B: recommendation, Level C:
Option/alternative, Level D: recommendation against, Level I: Insufficient evidence

302 Biostatistics: Literature Evaluation Kwasi Appiah Kissi

Title: should be succinct, non-biased, represents content of
study, and may indicate study design.
Abstract: Should be a brief description of goals, methods, results,
and conclusion. It is the summary of contents of study. It can be
structured (has specific subsections, easier to see sections, and is the
gold standard most journals use) or unstructured (long and difficult to
see results and methods).
Introduction: This is background information and helps to define
research question. You reference previous research that led to current
study. The last sentence of the introduction should state the study
objective (primary outcome).
Methods: This includes steps used to conduct study, subject
selection (inclusion [patients eligible to be in the study]/exclusion [those
who may be harmed in trial] criteria), baseline characteristics,
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randomization, binding, statistical tests used, treatment protocols, and
outcome measures.
Trial design: this should be clear in methods. There is
experimental (randomized controlled trial), observational (case-control,
cohort, cross-sectional), and meta-analysis.
Treatment protocols: Intention-to-treat analysis – statistical
analysis of all subjects according to group, which they originally
belonged. This is the stronger of the two protocols. Per protocol
analysis – statistical analysis on a subset of patients who completed the
trial. This can cause bias because patients with adverse effects could be
taken out.
Deficiencies in methods: These include inadequate
definitions/design (for subjects, treatments, evaluations), inappropriate
control group, inappropriate randomization, failure to use blinding (if
appropriate), or lack of objectivity in patient evaluation.
Outcome measures: Can be primary outcome (only the statistical
analysis preformed can be applied to this) or secondary outcomes (you
cannot detect a difference in endpoints because there is no power
calculation.
Results: This includes describing study’s findings; objective observations
(planned vs. post-hoc observations); No opinion or discussion; tables,
figures, graphs (baseline data); statistical vs. clinical significance; and
adverse effects.
Measures of central tendency: mean vs. median and SD vs. SEM
Measures of uncertainty: confidence intervals (degree)
Validity: Internal (researcher controls for all extraneous variables.
The only variable that influences results is the one the investigator is
manipulating.) vs. external (extent to which the results can be
generalized/extended to others.)
Assuring validity of data: baseline characteristics; avoid multiple
statistical comparisons; look for inconsistencies in tables, graphs,
abstracts, and text; sample size determination.
Study flaws: imbalance of baseline characteristics, endpoint not
specified in advance, no a priori determination of power, inappropriate
statistical tests, multiple subgroup analyses, selective reporting,
misleading graphs, or secondary endpoint analysis.
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Measures of clinical benefits:
Relative risk reduction – difference event rates between
control and treatment groups + event rate in control group.
Absolute risk reduction – difference in event rates
between control and treatment groups.
Number needed to treat (1/ARR) – number of subjects
who must be treated to benefit 1 patient.
Confidence interval: Prospective trial (CI with 0 indicates no
statistical difference) or Retrospective trial (CI with 1 indicates no
statistical difference and relative risk/odds ratio)
Discussion: Includes a brief review of findings relative to clinical practice,
description of clinical significance, limitations, problems in study design,
and may include conclusion.
303 Patient Counseling: HIPAA Eso Okosun
HIPAA stands for health insurance portability and accountability act. It was enacted
on April 14, 2003. It is required for all health professionals. There are five aspects to
HIPAA and they include:
a. Provides patients greater control over their health information
b. Limits the use and release of health information
c. Establishes safeguards to protect the privacy of health information
d. Establishes civil and criminal penalties for violations
e. Permits exceptions in the interest of protecting public health
PHI stands for protected health information while NOPP stands for Notice of privacy
practices
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303 Patient Counseling: OBRA 90 Wenda Bailey
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Legislation enacted in the 1990s that charged pharmacist to counsel
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Acronym OBRA 90 stands for: Omnibus Budget Reconciliation Act of 1990
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 Mandates that RPh performs prospective drug utilization review (DUR) when filling
prescriptions for ambulatory Medicaid patients
PHA 303 PATIENT COUNSELING: OBRA 90
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Pharmacy included in this legislation include:
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o
Community pharmacies
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o
Out-patient-hospital pharmacies
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Components of prospective DUR:
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o
Patient profiles
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o
Screening
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o
Patient counseling
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SPECIFICALLY OBRA 90 PATIENT PROFILE STANDARDS STATES:
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o A reasonable effort must be made by RPh to obtain, record and maintain at least the
following info regarding individuals receiving benefits under this sub-chapter:
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 Individual history where significant i.e. disease state(s), known allergies, drug rxn and a
comprehensive list of meds and relevant medical devices
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RPh’s comments relevant to the individual’s drug therapy
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SPECIFICALLY OBRA 90 SCREENING STANDARDS STATES:
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o The state plan shall provide a review of drug therapy before each rx is filled or delivered to
and individual receiving benefits under this sub-chapter, typically at the point-of-sale or point of
distribution
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o
The review will include screening for potential drug therapy problems due to:
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Therapeutic duplication
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Over – or under - utilization
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 Drug – disease contraindications e.g. a disease interfering with drug working or a drug
aggravating a disease or condition
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Drug – drug interactions, including serious interactions with non-prescription or OTC drugs
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Incorrect drugs dosage or duration of drug treatment
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Drug – allergy interactions
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Clinical abuse / misuse or irrational prescribing
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SPECIFICALLY OBRA 90 PATIENT COUNSELNG STANDARDS STATES:
Name, address, phone number, date of birth (or age) and gender
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o As part of the state’s prospective drug use review programs – applicable state law shall
establish standards for counseling of individuals receiving benefits – by RPh which includes at
least the following:
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 RPh must offer to discuss with each individual or caregiver such individual (in person,
whenever practicable or through telephone) who presents a prescription, matters which in the
exercise of the RPh’s professional judgment (consistent with applicable state law respecting the
provision of such info) deems significant including:
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Name and description of meds
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Dosage form, dosage, route of administration and duration of drug therapy
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Special directions and precautions for preparation and administration and use by the patient
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Common, severe side and adverse effects
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Techniques for self monitoring
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Proper storage
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Prescription refill info
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Action to take if dose missed
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 Nothing in this clause shall be construed as requiring RPh to provide consultation when the
patient refuses such consultation
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**OBRA 90 APPLIES TO AMBULATORY MEDICAID PATIENT VS. STATE REGULATIONS (GA STATE
LAW) APPLY TO ALL AMBULATORY PATIENTS**
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303 Patient Counseling: Prime questions for new prescriptions Eso Okosun
What did your doctor tell you the medication is for? This question promotes a discussion
of purpose
How did your doctor tell you to take the medication? This question promotes a
discussion of directions of use
What did your doctor tell you to expect? This question promotes a discussion of
expected outcomes
They are open-ended questions. They begin with what and how.
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303 Patient Counseling: Show and tell questions for refill prescriptions Eso
Okosun
It combines prime questions with final verification.
What do you take the medicine for?
How do you take it?
What kind of problems are you having?
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303 Verbal skills: Active listening Brad Mcdougal
1.) Listening requires effort and is NOT a passive activity.
2.) Listening has nothing to do with intelligence.
3.) There are two listening extremes Uncaring and Overly Involved, we want to be in the middle
At a stage called empathy.
4.) Empathy (listening well) requires:
a.) Searching beyond the content (facts) of a message to identify the intent
b.) Remaining nonjudgmental
c.)Responding in a way that conveys your understanding and objectivity
5.) Empathy is not simply “being nice”. It is not agreeing, nor disagreeing, it’s listening for intent.
6.) Positive Reassurance:
a.) Assurance that the medication is safe.
b.) Honest offer of assistance
7.) Ineffective Responses:
a.) Saying Nothing
b.) Distracting (changing the subject)
c.) Judging
d.) Advising
e.) Analyzing
f.) Negative Reassurance (Placating)
g.) Probing
8.) Resist the temptation to judge and advise. People want to be listened to and understood. Use
empathetic and helpful responses. Patients are experiencing illnesses on a physical and chemical level.
Also, on an emotional level being empathetic means responding to those emotions.
9.) Emotions related to Illnesses: Uncertainty, Dependency, Fear, Lack of Privacy, Loss of Idenity,
Isolation from usual Support systems, and Need for Meaning.
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1.)
2.)
3.)
4.)
5.)
303 Verbal skills: Assertiveness Brad Mcdougal
We must be assertive; this is the median between passive and aggressive.
Passive behavior is behaving in a way that allows your thoughts or feelings to be infringed upon.
Aggressive behavior is behaving in a way that violated the thoughts and feelings of others.
It is most difficult to be assertive when giving or receiving criticism.
During these situations we can be manipulated by either ourselves or others. We are manipulated
when we think:
a.
We are not responsible for our thoughts or actions
b.
We think that we must provide reasons or excuses for our behavior
c.
When we think we have to find solutions to others problems
d.
When we think we should not make mistakes
e.
When we think we need everyone to like us
f.
When people believe we should automatically understand someone
6.)
The Three-Part Assertive Message
a.
Describe the Situation – what you observed the facts. Understand other’s feelings or
position.
b.
Tell the person how you feel about the situation or how it affected you.
c.
Tell the person what you want, what you are willing to do, or both.
7.)
Things to avoid in the Three-Part Assertive Message
a.
Avoid Absolutes
b.
Avoid Judgment Words
c.
Avoid Personal Attacks
d.
Avoid Multiple Criticisms
e.
Avoid Advice/Answers
8.)
Ways to become more assertive using the Two-Part Assertive Response. We use this when
others are criticizing us or when others are making requests of us
a.
Show you have listened by using summary or reflection of feeling
b.
State your position, what you think, feel and are willing to do.
i.
Agree if you think criticism is valid,
disagree if not.
ii.
Inquire if you want to know more.
iii.
Use Fogging if you are unsure of the validity of
the person.
iv.
Use the Time-Out response If you are unsure
how to respond.
v.
Use the Broken Record response when
others won’t accept a no or yield.
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303 Verbal skills: Communicating with physicians Dame Tuyen Pippa
Nguyenskitt of Ho Chi Minhburg
1. Framework of a well stated recommendation
+ Introduction (self, patient, type of problem) – be direct, focused and not apologetic
+ Problem (describe the problem briefly and completely, discus the problem in terms of
possible cause and other signs/indications of problem)
+ Recommendation (background for advice, specific advice, discussion with physician).
Try to be non-threatening, and do not fake it if you don’t know the answers
2. Three-step approach to changing behavior when recommending less costly therapies
+ Emphasize efficacy (drug B = drug A)
+ Mention secondary benefits (reduced toxicity, reduced need for monitoring, greater
patient comfort, etc.)
+ Mention financial benefits (less costly)
3. Solutions to handle physicians’ objections
+ practical objection -> welcome them
+ stalling objection (psychological) -> force the physican’s hand “I understand you need
more time. I’d be happy to clarify anything you are unclear about.”
+ no need solution (psychological): physician is satisfied with current therapy choice ->
lead back to presentation point “It is understandable that you want to stick with your
current choice. I’d like to show you why you might want to try the new therapy.”
+ source objection (psychological): physician is objecting towards pharmacists ->
pharmacists need to keep relationship with physicians over time to build trust
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303 Verbal skills: Communicating for Compliance Dame Tuyen Pippa
Nguyenskitt of Ho Chi Minhburg
1.Evidence used to recognized noncompliance
Objective (obtained from sources other than patient)
+ medication profile (refill record)
+ compliance devices
+ drug concentration levels
+ signs and symptoms of disease
Subjective (obtained from interaction with patient)
+ pink flags (subtle statements that signal possible non-compliance)
2.Recognizing noncompliance
** When subjective evidence exists
+ use reflecting responses (It sounds like…/I hear you complaining…)
+ follow up with open-ended questions, universal statements (everybody has trouble
with…/this is a very common concern…/many people bleive…), symptomp probing (I
noticed that…/I’m concerned that …)
+ remain non-judgemental
** When objective evidence exists but not subjective
+ use supportive compliance probing
+ remain non-judgmental
3.Identifying causes of noncompliance
+ knowledge deficits (when patient is misinformed ab a drug): use prime questions,
show and tell questions
+ practical impediments: use non-threatening questions, reflective responses, universal
statements, key symptoms questions (this is when side affects occur) including location
(Where is it?), severity (How bad is it?), timing and duration (when do you have
symptom? How often? How long does it last?), onset (When did it start?), associated
symptoms, modifying factors (What makes it better or worse?), context (Under what
circumstances do you experience symptom?)
+ attitudinal barriers (when patient is resistant to taking a drug): use open ended
questions that focus on patient’s belief, use reflecting response
4.Managing non-compliance
+ for knowledge deficits: provide written and verbal information, use summary
statements, verify understanding
+ for practical impediments: simplify schedules, reminder aids, consule with prescriber if
patient has adverse effects
+ for attitudinal barriers: start with empathy, engage patient as an active participant,
negotiate course of treatment with goals, use health and quality of life as incentives
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303 Medication interview: Ordering of information Jared Safran
The flow chart for the medication history interview consists of...
Introduction (name role, purpose, time it could take, and ask for permission)
Medical Conditions and Medications (list conditions, current meds and organizing
statement where you essentially say lets discuss one at a time)
Condition #1 (how long was it present)
Current Medication for #1 for condition #1 (name, how long, how is it taken be
specific, if noncompliance detected list causes, does the med help, side effects for ADE,
disease monitoring in other words, how is the patient monitoring his condition)
(repeat for each current med for condition #1)
Past Meds for condition #1 (name, reasons discontinued)
Non-prescription drugs and Herbals (name, how is it taken, side effects)
Alcohol/Tobacco/Caffeine (explain why asking, types used, how much/quantity) (good
strategy here is “i need to find out about alcohol uses as they can affect your
medications”)
Allergies (drugs and foods and be sure to describe reactions)
Closing (goals met, summary of info gathered, address patients questions, thank
patient)
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303 Medication history interviewing: Questions to ask about prescription
medications Jared Safran
Meds for condition #1
name of the medication?
how long taking?
how is it taken? (specific)
if non-compliance detected, causes?
Does it help?
Side effects and adverse events?
Disease state monitoring.
DON’T forget to ask about PAST medications for same condition (name and
reason it is no longer being taken)
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303 Medication history interviewing: Allergies Megan Jacobson
From the Flowchart for the Medication History Interview
Ask patient about any reaction to any drugs. Ask them to describe any allergy or
reaction they encounter.
Ask patient about any reaction to any foods they have had. Ask them to describe any
reaction they have encountered.
303 Medication history interviewing: Alcohol/tobacco/caffeine Megan Jacobson
Explain why you are asking about about their alcohol/tobacco/caffeine use. (You are
asking this because alcohol/tobacco/caffeine products can influence drug interactions or
increase the likelihood of side effects. It is not a judgement - just for informational
purposes.)
Ask what types are used and in what quantities. You will be able to use this information
objectively in your assessment of their medications later and it helps to create a full and
complete history of all substances used.
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305 Accounting: Measurement of Income Robert English
Income= Revenue – Expenses
Income= Profit!!!
Income is increases in economic benefits during the accounting period in the form of inflows or
enhancements of assets or decreases of liabilities that result in increases in equity, other than
those relating to contributions from equity participants
INCOME TERMINOLOGY:
·
Revenues -- Inflows and enhancements from delivery of goods and services that
constitute central ongoing operations
·
Expenses -- Outflows and obligations arising from the production of goods and services
that constitute central ongoing operations
·
Gains -- Like revenues, but arising from peripheral transactions and events
·
Losses -- Like expenses, but arising from peripheral transactions and events
How and when is income measured in the accounting period?
How?
Audits, financial statements, income statements, income statement, and balance sheets are all
ways to measure income.
When?
Monthly, quarterly, biannually, annually (depends on the business).
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305 Accounting: Preparation of Income statement and Balance sheet Ryan
Pate
Income Statement:
Summary of income earned during accounting period.
The result of operations for the accounting period.
To construct, use revenue and expense account balances.
Six sections:
Example: Stone Drug Company
1. Heading
2. Revenue
3. COGS
4. Gross Margin
5. Expenses
6. Net Income
At the end complete closing entries.
Balance Sheet:
Presents the financial position of a business at a particular point in time.
To construct use all asset accounts, all liability accounts, and OE accounts of contributed capital
and retained earnings. (The revenue and expense accounts have been closed.)
Five sections
Example: Stone Drug Company
1. Heading
2. Assets
3. Liabilities
4. Owners Equity
5. Liabilities + Owners Equity
Retained Earnings is the link between the income statement and the balance sheet.
Accounting Cycle
Throughout accounting period:
1. Record transactions
Last day of accounting period:
2. Adjusting entries
3. Income statement
4. Closing entries
5. Balance sheet
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305 Accounting: Accrual vs Cash system of accounting Ryan Pate
Accrual System of Accounting: Transactions are recorded at the time they occur.
Cash System of Accounting: Transactions are recorded once cash changes hands.
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305 Accounting: Fundamental accounting Equation and definitions Monica
Elliott
Accounting Module Objectives:
1.
Define and differentiate the terms accounting, auditing, and bookkeeping.
Auditing: verify records and computations
Bookkeeping: documents resources in, out and claims to the resources.
2.
Define and differentiate the accrual method and cash method of recording
transactions.
Accrual: record when transactions occur (money may change hands later)
Cash: record when money changes hands
Differences between accrual and cash systems matters when you measure income.
The “Matching Principle” says we should use the accrual system because it matches revenue
earned to expenses incurred to generate that revenue.
3.
Define and differentiate revenue and expenses.
Revenue: measurement of goods sold or services rendered for which the business receives
cash or the promise of cash or something of value (bartering).
Expenses: Measurement of resources used up during a period of time in order to earn revenue.
4.
Define and recognize asset accounts, liability accounts, and owner equity
accounts.
Asset Accounts: resources owned by the business. Examples of asset accts are: cash, accts
receivable (receive in the future), building, inventory, equip, pre-paid insurance
Liabilities Accounts: debts owed by business to creditors. Examples of liability activities are:
borrow cash, purchase goods on credit (wholesaler and you pay later). Examples of liabilities
accts are: notes payable, accounts payable.
Owners Equity/Networth Accounts: The claim of owners to the assets the business after the
creditors have been paid. Examples of owners equity activities include: increase when owners
invest in the business (contributed capital), decreases when expenses are paid. Examples of
owners equity accts include: telephone expense, salary expense, contributed capital, sales or
service revenue.
5.
Explain the fundamental accounting equation.
A = L + OE
[Assets = Liabilities + Owners Equity]: this gives an economic description of the business.
All transactions have a dual effect on the business.
Purchasing assets with cash or credit negate the owners equity (you had to use resources to
purchase the asset)
If you reduce liability you must reduce an asset.
Expenses are not liabilities. Expenses are a measurement of resources used up.
6.
Explain how amounts are added to and deleted from “T” accounts
A “ T ” account is used to add transactions to accounts. There are 3 questions to ask when
recording a transaction to a “T” account.
a)
What accounts are affected?
b)
How is the heading (A, L, OE) affected? Place on Db or Cr sides based on your response.
c)
After placing #s, does Db = Cr?
7.
Define debit and credit.
Debit = LEFT
Credit = RIGHT
Doesn’t mean negative or positive. They are reversed based on what side of the eqn they’re
on.
8.
Explain the effect on “owner equity” of owner contributions to the business, the
earning of revenue, and the payment of expenses.
Owner contributions: Assets Increase (Db); OE Increase (Cr)
Earning of Revenue: Assets Increase (Db); OE Increase (Cr)
Pymt of Expenses: Assets Decrease (Cr); OE Decrease (Db)
9.
Given a description of a transaction, journalize and post to the proper accounts.
n/a
10. Determine the balance of an account and preform an “unadjusted” trial balance.To
determine the balance of an account total the Db and Cr sides. Add these together, and see
where the balance lies (either Db or Cr) using the appropriate pos/neg signs on either side of
the eqn. (+Db) A (-Cr) = (-Db) L (+Cr) + (-Db) OE (+Cr)
11. Define and differentiate fixed and current assets.
Fixed Assets: tangible, long-living resources. Examples of fixed assets include: bldg.,
machinery, fixtures, equipment
Current Assets: resources owned by the business that are expected to be realized or consumed
or sold in one year. Examples of current assets include: cash, accts receivable, inventory
12. Explain why and when adjusting entries are made.
Adjusting entries are made on the last day of the accounting period in an effort to report all
expenses. More expenses recorded = lower income = lower income taxes. There are 4 typical
types of adjusting entries which include: inventory, salary, depreciation and pre-paid insurance.
13. Given and adjusting entry, record it in the proper accounts. n/a
14. Perform an “adjusted” trial balance. n/a
15. Explain how and when income is measured in the accounting period.
Income is measured after the “adjusted” trial balance is calculated.
Income = Revenue - Expenses
16. Describe what information the income statement presents, i.e. its purpose.
The purpose of an income statement is to determine net (or final) profit.
17. Name/recognize the accounts that are used in preparing the income statement.
Revenue, cost of goods sold, expenses.
18. Name and describe the six major sections of an income statement.
Heading: includes name of the business, the title and the date/time period
Revenue: Sales and service revenue
Cost of Goods Sold: balance of expense required to purchase goods for resale. (Can include
transportation expenses)
Gross Margin: calculation that is inserted = Revenue – Goods
Expenses: balances of remaining expenses are listed. List individual expenses and then total.
Net Profit: also called income. Net=Final. Can be viewed 2 ways:
1)
Revenue – All expenses
2)
Gross Margin – Remaining expenses.
Net Income: (used in corporations) Net profit – Income Tax = Net Income
19. Explain why and when closing entries are made.
Data collected for current accounting period only. The balances are transferred to an account
called “retained earnings” (OE). This is done on the last day of the accounting period and is
known as closing entries. This allows the business to measure income to for the next
accounting period.
20. Explain the purpose of the retained earnings account.
The retained earnings account allows for all expenses to be paid off, as well as, close the
revenue (service and sales) account to be closed. The retained earnings account is an OE
account.
21. Given a closing entry, record it in the proper accounts. n/a
22. Describe what information the balance sheet presents, ie, its purpose.
The purpose of the balance sheet is to show what the business owns and owes on a specific
date (or accounting period).
23. Name/recognize the accounts that are used in preparing the balance sheet.
The accounts used for the balance sheet are all asset accounts, all liability accounts and OE
accounts of owner contributed capital and retained earnings. All revenue and expense
accounts are closed out and are NOT used.
24. Name and describe the five major sections of the balance sheet.
a)
Heading (name, title, date)
b)
Assets Section (grouped current and fixed, then totaled)
c)
Liabilities Section (current and long-term, then totaled)
d)
Owners Equity Section (contributed capital and retained earnings, then totaled)
e)
Sum of L + OE to verify L + OE = A
THE ACCOUNTING CYCLE:
I.
Recording of transactions (starts day 1 of accounting period through last day of
acct period)
II.
Adjusting Entries(done the last day of the accounting period. These are made
to ensure all expenses are reported to reduce income tax)
III.
Income Statement (measures result of operations)
IV.
Closing Entries (empty revenue &expense accounts
V.
Balance Sheet (determines what the business owes and owns)
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305 Accounting: Fundamental accounting Equation and definitions Monica
Elliott: Same as above.
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305 Financial Analysis Purchasing: Financial Ratios
2 types of financial analysis: Comparative Analysis and Ratio Analysis
Comparative Analysis:
 Express each financial statement component as a percent of sales.
 Compare with Digest data
Financial Ratio Analysis consists of:
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Completing a financial ratio analysis
Properly segmenting the ratios compiled
Comparing these ratios with ratios for the same enterprise during recent years
Comparing these ratios with a similar group of pharmacies as reported in the NCPA Digest
Writing a financial ratio analysis report which describes the problems in all major areas of
managerial control
 Listing specific financial objectives
Compare data with previous years to figure out trends occurring. Consists of taking individual
compartments of Balance sheet and Income statement and relating them one to the other and
calculating various ratios.
Major areas of ratio analysis:
 Solvency
 Efficiency
 Profitability
Solvency is the overall ability of the firm to pay its legal debts.
Efficiency is how well the manager is using available capital.
Profitability is the proverbial “bottom line.” An important, but not only, measure of business success.
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305 Financial Analysis Purchasing: Net profit Jennifer Niemeier
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Total amount made by the company after expenses have been factored (with the
exception of tax).
Net profit = Gross margin – remaining expenses = revenue – all expenses.
Net profit vs. Net income: net = final; net profit – income tax = net income, while
sole proprietorships and partnerships who don’t pay income tax have equivalent
net profit, net income numbers.
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305 Financial Analysis Purchasing: Cost of Goods Sold Jennifer Niemeier
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Cost of goods sold: list inventory expenses and transportation expenses if those.
Gross margin = Revenue – COGS (cost of goods section).
Pharmacy purchases are 75% COGS.
Part of the Income Statement.
If COGS goes down, then our profits should be going up in the NCPA Digest
Comparisons.
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305 Financial Analysis Purchasing: Break-even Analysis Elizabeth Gibson
Break-Even Analysis
Definition of Break-Even point: That point in terms of sales or months wherein no profit or loss
is realized
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Utilization
o Financial analysis comparison year to year
o Determine how much in additional sales are necessary to cover (pay for) a new
expenditure or program (ex. more staff, immunization program, etc.)
o Determine how much in additional sales are necessary to reach a Net Profit
Target
o Sales-COGS=GPM-VE-FE=Net Profit
Steps of Break-Even Analysis
o Gather data from Income Statement
 sales, COGS, Gross Profit Margin
o Classify Expenses
 Variable expenses
 Fixed expenses
o Determine Margin Income Ratio per dollar of Revenue earned
 Sales-COGS=GPM
 Get a percentage of GPM of total sales
 Then, to get MIR %GPM-%Variable expenses
o Determine the Break-Even point in dollars and months
 Fixed costs/MIR=Break Even Sales
 Break Even sales x 12 = Break Even point in months
305 Financial Analysis Purchasing: Discounts Elizabeth Gibson
Discounts
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Cash
o
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Amount deducted when an invoice is paid within a specified period of time
Usually 2%
notation 2/10, N/30
 This means you will get a 2% discount if paid within 10 days and NO
discount if simply paid within 30 days
o Cash discounts are VERY important if you have 2.75 million in annual sales and
1.9 million in purchases, and you 2% discount saved you 38,000, and calculated
MIR that discount amounts to 237,500 in sales
Quantity
o A discount where when you buy a certain quantity you obtain a discount
 ex. 4 cases vs. 1 case
o Also classified as a "Deal"
o Robinson-Patman Act prohibits price discrimination unless justified
o To determine if a "Deal" should be purchased, you need to analyze the numbers
 Key lies in extra capital used, turnover rate, and ROI (Return on
investment)
 If the ITOR is > 3 and the ROI is > 35% the "Deal" SHOULD be
purchased
o Also should consider Carrying (opportunity) cost
 This is .5-1% of cost of inventory/week=Inventory cost on shelf
Trade
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o This is an amount deducted from the list price
Serial (Combination)
o More than one discount
o Example of notation 40,10,1
 This means that 40% is discounted, then that discounted price is reduced
by 10%, and then that price is reduced by 1%.
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305 Human Resource Management: Antidiscrimination law Rebecca Wilson
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Human Resources Mgmt: Anti-discrimination Law
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Discrimination in the work place is defined as recognizing differences or distinctions in
people. Discrimination is lawful when it is based on legitimate business needs.
Discrimination in the workplace becomes unlawful when it is not based on legitimate
business needs.
Anti-discrimination laws protect against discrimination based on:
Race, color, religion, sex, national origin, age, pregnancy and disability. Each of these is
referred to as a protective class or category.
4 major federal laws attempt to provide protection against discrimination the workplace:
n Title VII of Civil Rights Act of 1964
n Age Discrimination in Employment Act of 1967 (ADEA)
n Pregnancy Discrimination Act of 1978 (PDA)
n Americans with Disabilities Act of 1990 (ADA)
The federal laws apply to both public and private businesses based on the # of
employees (roughly 15 or more employees)
n Any business, public or private
n Title VII:
with 15+ employees
n ADEA:
with 20+ employees
n PDA:
with 5+ employees
n ADA:
with 15+ employees
Equal Employment Opportunity Commission (EEOC) is charged with enforcing the
Federal anti-discrimination laws.
The enforcement steps are:
1. Investigate charge
2. Negotiate settlement
3. Criminal court
4. Civil court
n The penalties for violations consist of Reinstatement, Back pay, Fringe benefits,
Reasonable attorney’s fees, Compensatory damages, and Punitive damages.
Title VII of Civil Rights Act of 1964:
Prohibits discrimination in hiring, firing, compensation, and terms, conditions or
privileges of employment on the basis of race, color, religion, sex, or national origin.
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Two types of unlawful behavior by employers: Unequal treatment and unequal impact
Unequal treatment: Applying different standards to different employees within a
protected class/category
Unequal Impact: Treating all people the same, does not guarantee the results will be the
same.
Burden of proof is on the employer
Interview questions should address relevant job criteria
Exceptions to Title VII include
n Bona fide occupational qualifications
n Seniority systems
n Preferential treatment systems
n
BFOQ: Employers are permitted to discriminate if there is a justified business reason.
Customer preference does not constitute a BFOQ.
Seniority systems can discriminate if the system was not created to intentionally
discriminate.
Preferential treatment systems
n Set aside a portion of opportunities for minorities and women who have been victims
of discrimination previously.
n Affirmative action.
Age Discrimination in Employment Act of 1967 (ADEA)
n It is unlawful for an employer to fail or refuse to hire, to discharge, or otherwise
discriminate because of age against individuals 40 years of age or older with respect to
compensation, terms, conditions, or privileges of employment.
n It is unlawful to forcibly retire an employee because of age 40+.
n It is unlawful to give preference because of age to one person over another within
the protected age group.
Exceptions to the ADEA
n Bona fide occupational qualifications (BFOQ)
n Unequal impact on the protected age group
n Seniority systems
Age as a BFOQ is permitted but extremely rare.
Unequal Impact
Job requirements with an unequal impact on the protected age group are
permitted if truly necessary.
Pregnancy Discrimination Act of 1978 (PDA)
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n Women affected by pregnancy must be treated the same as other applicants and
employees on the basis of their ability or inability to work.
n Employers could no longer require women to take leaves of absence or resign
because of pregnancy.
n Health insurance provided must cover expenses for pregnancy-related conditions on
the same basis as expenses for other conditions.
n Specific guidelines for pregnancy leave.
PDA Guidelines for Pregnancy Leave
Employers may NOT:
n Use any employment practice (hiring, work duties, work schedule, promotion, firing,
etc.) that discriminate against applicants or employees because of pregnancy, childbirth,
abortion or a planned adoption.
n Treat disabilities related to pregnancy or childbirth differently from other types of
disabilities or medical conditions.
Work parameters can be changed during pregnancy If pregnancy renders the employee
unable to do the job or If pregnancy endangers the health and safety of others.
An employee cannot be considered unable to do her job unless the particular skill
affected must relate to the central mission of the job. The employer must treat her the
same as temporarily disabled employees.
If pregnancy endangers the health and safety of others the employee can be reassigned
or put on mandatory leave. Does not apply to safety of employee or fetus - - only third
parties.
Family Medical Leave Act of 1993 (FMLA)
n Requires employers of 50 or more workers to provide up to 12 weeks a year of
unpaid, job-protected leave to take care of a newborn or newly adopted child.
n The leave could also be used to take care of a sick child, spouse or parent, or
because of the employee’s own serious illness.
Americans with Disabilities Act of 1990 (ADA)
n Prohibits discrimination against a qualified individual with a disability in any areas of
employment, including: hiring, promotion, discharge, and other terms and conditions of
employment.
n Restricts use of pre-employment medical exams and inquiries and requires employers
to reasonably accommodate individuals who are mentally or physically impaired, have a
record of impairment, or are perceived to be impaired.
n Prohibits discrimination in public services (especially transportation), public
accommodations, and telecommunication services.
The goal of the ADA is to help disabled persons support themselves by removing
barriers to employment and improving access to public accommodations.
A disabled person has a physical or mental impairment that substantially limits
him/her in a major life activity, e.g., employment.
n Includes those who have a record of impairment.
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Alcoholics Are protected under ADA (if they can perform essential functions).
Employer can require they not use alcohol at work or be under the influence at work.
Does not require employers to provide rehabilitation programs.
Current drug abusers are not protected under the ADA regardless of whether it affects
ability to perform. Does not require employers to provide rehabilitation programs. Past
drug abusers are protected (if no longer using and rehabilitated).
Smokers are not protected under the ADA.
Lifestyle discrimination statutes: Employers cannot discriminate based on a
legal,
off-the-job activity, such as smoking.
Under the ADA homosexuals, people with sexual disorders, and compulsive gamblers
are excluded from coverage. However, the local and state laws may offer protection.
In order to be protected by the ADA, an employee must be able to perform the essential
functions of the job when reasonably accommodated by the employer.
Employers are not required to provide accommodations presenting an undue
hardship. Accommodations causing significant difficulty or expense to the
employer are an undue hardship. The EEOC examines case by case.
Cannot ask questions regarding disability in the interview. Can ask applicant to
describe/demonstrate how s/he will perform the essential functions of the job with
or without accommodation. If a disability is claimed but not apparent, ask for
certification. Physical exams can be required but only after a post job offer. Only
if usually required of all candidates.
The individual with the disability has the obligation to request the
accommodation.
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305 Human Resources Management: Privacy in the workplace Rebecca
Wilson
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There is no specific federal legislation mandating an employee’s right to privacy.
However, 2 pieces of federal legislation are relevant. These are U.S. Constitution –
4th Amendment, Privacy Protection Act of 1974.
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The U.S. Constitution (4th amendment) guarantees privacy and prohibits
unreasonable searches and seizures by the Government. It was written to protect
the individual. It protects employees of the Government, i.e., public sector.
An employee’s privacy in the private sector is not mentioned in the U.S.
Constitution, not mentioned in most state constitutions, not mentioned in GA
State Constitution.
The bottom line is there is little legal support in the private sector for an
employee’s right to privacy.
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The Privacy Protection Act of 1974 Established the Privacy Protection Study
Commission, which made recommendations (but no laws) for private employers in
three areas:
n Record Review
n Review regularly
n Discard inaccurate information
n Examine disclosure process
n Employee Access
n To his/her performance evaluations
n To documents s/he signed
n To his/her medical records
n Not to confidential references
n Outside requests
n Do not provide payroll information
n Do not provide drug test results
n Do not provide consumer reporting information
Criminal Defamation is defined in GA State Constitution as ruining a person’s
good name, communicating false information without a privilege to do so.
Employer’s defense: Information revealed on a “need to know” basis.
Invasion of privacy is defined in the GA State Constitution: a private place is a
place where one can expect to be safe from intrusion. In a private place, it is
unlawful to eavesdrop, observe, intercept a private conversation, activities out of
the public view, private messages. Workplace is property of employer. Employee
can expect privacy only in: Personal belongings and Locked items.
Screening activities are of 2 types: Background Investigations and Polygraph
tests.
Background Investigations:
Accuracy is critical
“Catch 22” of references
Potential employer wants information. Former employer fears defamation suit.
Use waivers. Don’t ask about Applicant’s criminal record
n Ask about job related convictions, not arrests
n Any question should be job related
n Rule of thumb: Limit access to a “need to know” basis
Polygraph tests
Employee Polygraph Protection Act of 1988 prohibits private employers from
using polygraphs. Businesses exempted from EPPA include
n Firms with on-going investigations of theft
n Security firms
n Firms that handle controlled substances
AIDS Testing:
n Difficult to justify for employment purposes
n HIV+ protected under ADA
n Not spread through routine work
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n HC workers are protected by following guidelines issued by the CDC and mandated
by OSHA.
n Maintain confidentiality.
Drug Testing
n Recommendations for employers
n Test only applicants whose jobs are safety specific.
n Obtain valid consent, provide examinee with results.
n Maintain confidentiality, retest “+ results”.
n Random testing of current employees is difficult to justify.
n Justified: current employee, under reasonable suspicion, for a work-related incident.
If an employee tests positive for drugs
n Current employee tests “+” for drugs.
n Employee joins rehabilitation program.
n Employee claims no longer using.
n Employee attempts protection under ADA.
Substance abusers in the work place are a danger to the public, employer liable
for wrongs/negligence
General Guidelines:
n Develop a policy
n Document lessened performance
n Deal in private
n Explore rehabilitation as an option
n Employees “under the influence” should not drive
n Pharmacists who are substance abusers
Employers Defense Strategies
n Need to know
n Lack of Publicity
n Employee consent in writing
305 Human Resource Management: Employee behavior problems
Johnathon Barnett
Examples include chronic rx errors, absenteeism, theft, insubordination, and may result
in financial loss
2 types: performance problems (to prevent use job description, standards, and
appraisal form; to correct use motivation) and conduct problems (to prevent use
handbook; to correct us progressive discipline)
Correction through motivation based on: Motivation-Hygiene Theory or Hierarchy of
Needs Theory
Motivational techniques include: disclosing financial information, asking for input and
listening, assigning responsibility, drawing up a development plan, providing continual
feedback, providing financial awards for success, providing non-cash awards for success,
personally recognizing success, providing the right tools and physical environment,
minimizing personal distractions, and treating temps like regular staff
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When motivation fails, use the formal corrective interview.
Progressive Discipline – counseling, oral warning, written warning, suspension,
discharge; This can begin at any step, based on severity of infraction.
Employment at Will – The employment relationship may be ended at any time, by either
the employee or employer, for any reason, or for no reason at all, provided there is no
written employment contract covering a fixed term of employment. Exceptions to
employment at will include: anti-discrimination laws, public policy exceptions, and
implied contracts.
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305 Human Resource management: Sexual harassment Johnathon Barnett
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Awards included: back pay, damages, promotions, reinstatements
Managers and owners should recognize, prevent, and resolve.
Prohibited sexual harassment – “unwelcome sexual advances, requests for sexual
favors, and other verbal or physical conduct of a sexual nature…” (EEOC)
Definition expanded: non-sexual activity that is hostile and intimidating and gender
directed
Title VII (Civil Rights Act) – Prohibits discrimination on the basis of gender, race, color,
religion, or national origin in any employment condition (hiring, firing, promotion, and
compensation). This applies to public or private businesses with 15+ employees; most
states have lowered this threshold; Georgia has not.
Gender discrimination is sexual harassment.
Types of harassment (EEOC) – Quid pro quo (Latin for compensation) and hostile
working environment
Quid pro quo – the victim is forced to choose between submission to the sexual
demands of a supervisor or the loss of a job or job benefits.
31% of female workers are sexually harassed by males.
7% of male workers are sexually harassed; of these 40% are harassed by males and 60%
harassed by females.
Hostile work environment occurs when: the activity complained of is pervasive or
severe, creating an intimidating or abusive workplace.
Reasons for employee reluctance include: fear of reprisal, embarrassment, blaming self,
others not objecting, and a fear label being applied to them (being known as a
“troublemaker”)
Harassers of women: 28% seniors, 44% supervisors, 8% juniors, 20% at the same level
Office romances should not be forbidden; could lead to invasion of privacy claims
(lifestyle discrimination statutes).
49% of female pharmacists are harassed at work; of these colleagues, patients, and
supervisors equally contribute (33.33% each).
Actions taken by female pharmacists: 24% told supervisor, 44% confronted harasser, 9%
unknown, 8% changed shift, 15% changed employment
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Workplaces should have sexual harassment policies in place to prevent harassment.
Proper investigation of harassment will: reduce or absolve employer liability, dissuade
legal action, and facilitate internal resolution
Guidelines for investigation: investigate immediately, investigate discretely, interview
complainant, interview the accused, make a determination and take action, preserve all
evidence
Key points to understanding sexual harassment:
1. The activity complained is of a sexual nature.
2. Harassment can be toward the opposite sex or the same sex.
3. The activity must be unwelcome. (A voluntary relationship isn’t always
welcome. Whether the activity was solicited, desired, or encouraged is what is
relevant.)
4. Quid pro quo harassment forces a victim to choose between submission to
sexual demands of a supervisor or loss of job or job benefits.
5. Hostile work environment occurs when the activity complained of is pervasive
or severe, creating an abusive workplace.
6. A hostile work environment does not necessarily require physical touching and
does not require the harassment be aimed directly at the victim.
7. Employers are liable for the sexual harassment acts of employees (supervisors
and their subordinates) and customers/patients.
305 Human Resource management: Delegation Meagan Bruni
Being a manager in a Pharmacy, there are many things to be done all at once. One way to manage time
is to delegate tasks to others and make the best use of technicians. To best manage employees and be
able to delegate responsibility to them, a manager must establish and clarify expectations, link the
individual's work to larger organizational goals, set performance objects, and provide feedback and
coaching. Delegating to others and assigning responsibility is also a good motivator for employees with
performance problems. This gives them more pride in the organization and sense that if the business
succeeds, they too will succeed.
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306 Medication use: Medication safety Kara Williams
Storage: Temperature (monitoring, power outage plans), separation of LA/SA (look
alike/sound alike) drugs, expiration dating, security all important
Problems with Dispensing: pharmacist must gather information from patients, record
information in patient database, clarify questions and discrepancies, prepare medications
for patients, counsel patient about correct use, monitor patients
Prescribing: Pharmacists can play a clinical role in product selection and dosing
Preparation: unit dosing, sterile compounding, chemotherapy/hazardous materials,
labeling, cart fills, pharmacist verification
Administration: The Five Rights:
1) Right patient
2) Right drug
3) Right dose
4) Right route
5) Right time
Documentation: pharmacist is responsible for communication with prescriber,
interventions and drug recommendations
Reporting of Drug problems and ADE: Voluntary reporting systems (should be a culture of
safety (aka non-punitive)), MedWatch, Joint Commission (serious sentinel events), the state
(permanent harm or death), manufacturer
Medication Error: preventable events that occur at any stage in the medication use process
resulting in patient harm (ADE) or inappropriate medication use
Ø Drug Related Problems:
o Error of Commission
§ Correct Drug
· Subtherapeutic dosage
· Over-dosage
· ADE
· Drug interaction
§ Incorrect Drug
· Improper Drug selected
· Drug use without indication
o Error of Omission
§ No Drug
· Untreated condition
· Failure to receive prescribed drug
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306 Practice: Medicare – Medicaid Marissa Hatcher
o S: subjective findings
o 0: objective findings
o A: assessment
o P: plan (recommendations, education)
• Why perform pharmaceutical care: Identifies, resolves, and prevents MRP's (medication related
problems)
• Medicare I Medicaid
Medicare (11/10/05)
•
Medicare Part A -(SSA 18) subsidized thru social security, no premiums; disabled people
eventually covered in 1973; financed through payroll taxes; Services include: skilled nursing facility
care, home health care, hospice care, inpatient hospital care, short term nursing home stay
•
Medicare Part B -(SSA 19) partially funded by the government and other part covered by
monthly premiums paid by the patient; physician and other outpatient services covered;
supplementary medical insurance; financed from general revenues of federal government
•
Medicare Part D -prescription plan; premium must be paid; initiated by the Medicare
Prescription Drug Improvement & Modernization Act of 2003
•
• Medicare prescription drug, improvement, and modernization act (MMA) of 2003
• o Establishes Rx benefit for Medicare beneficiaries to be implemented Jan 2006
• o Beneficiaries are seniors/disables who receive social security benefits
•
o Categories:
•
Part A -hospital
•
Part B -Medical
•
Part C -Rx + medical (together)
•
Part D -only Rx
• o Prescription Drug Plans (PDP) are those responsible for providing the benefit; can
negotiate prices from pharmaceutical manufacturers without creating government control:
•
* * * * Standard Drug Coverage: • monthly premium = varies by plan and
level of benefits offered
•
• annual deductible = $295 • 25% coinsurance • initial coverage
limit =$2700 • catastrophic coverage after $4350 in out ofpocket expenses • or
$56154 total
•
•
•
••
•
between $2700 and $6154, the senior pays out of pocket annual coverage
•
*** each geographic "area" must have at least 2 plans to choose from
•
o Auto-enrol1ment -dual eligibles are auto-enrolled
• Dual eligibles -have bother Medicare and Medicaid; will no longer receive benefits
thru Medicaid but thru Medicare part
D
o Dispensing fee -costs to fill an Rx; PDP tells the phannacies how much they will reimburse
•
them
•
o Plans are required to meet TRICARE access standards in the state which they operate and
patients must have convenient access to pharmacies
o *****Any willing provider -PDPs required to permit pharmacy willing to accept the plans
terms and conditions participate in the plan's formulary network (preferred pharmacy has
lower copay than non-preferred); there is a standard contract for all phannacies but contract
can be modified by geographic region and type ofpharmacy
o Level Playing Field -plans must allow beneficiaries to obtain their
benefits from either a community phannacy or a mail-order ~"--'~-' pharmacy (ex:
90-day supply) ...-.--~-...------.--.~~
•
o Out-of-network phannacy access -beneficiaries can obtain their drugs from out-of-network
providers ifthey can't reasonable obtain their meds from a network phannacy (must send in a claim
for reimbursement)
•
o Medication therapy management programs -PDPs must establish a MTM program with
"multiple chronic diseases" and the likelihood ofincurring high annual costs (high annual cost for
2006 is $4000.00); MTM programs are developed by pharmacists and physicians and run by any
willing healthcare provider
•
o Once enrolled, locked in for one year. Ifenrolling late, there is a late fee which will accrue
th
over time. Have 62 days to enroll after 65 birthday or after loss ofinsurance coverage thru employer.
•
o Retiree benefits plan options:
• Employer can continue to provide Rx benefits that is minimally equivalent to Medicare Part
D (incentives given to employers who continue Rx coverage to employees)
• Contract wi PDP to offer Rx drug benefits to retirees eligible for Medicare
• Supplement the new Medicare benefit
•
o Changes to formulary, preferred drugs, or co payment status ofa drug must be announced
30 days before it occurs to give time to accommodate change
•
o Formularies must include drugs within all therapeutic categories and classes
•
o Pharmacy & Therapeutics committee with practicing physicians and phannacists
representing various clinical specialties meet at least
•
. quarterly to make decisions regarding what's in the formulary; decisions made based on
scientific evidence and/or pharmacoeconomic considerations
•
o NOT Covered my Medicare: barbiturates, benzodiazepines, anorexia or weight losslgain
meds, fertility agents (?17), cosmetic agents,
54
symptomatic relief of cough/cold, non-Rx meds, drugs payable
under Medicare part A or part B
o *** Dual-eligibles -currently hold Medicare and Medicaid coverage ,
automatically assigned to a PDP plan unless chooses one during emollment
period; plan co pays DO NOT have to be waived and pharmacies DO NOT have
to dispense the medication
o PACE plans -Program ofAll Inclusive Care for the Elderly receives funding from Medicare Part D
instead ofMedicaid
o Pharmacies must dispense lowest priced generics available
o Law required Part D plan sponsors to maintain records for 10 years (including prescriptions) and
law requires that PDP sponsors issue a standard benefit ID card to emollees
Medicaid
•
•
•
•
•
•
•
•
•
•
Medicaid -eligible poor; controlled by"the.stat~~? not federally
Each state sets their won Medicaid eligibility requirements
• Mandated Categorically Needy:
o Aid to families with dependent children (AFDC)
• Eligibility criteria:
• Maximum limit on family income and resources; set by each state
• o Individuals who receive chase assistance through Supplemental Security Income (SSI)
Program
• o Several other groups (low income that don't meet AFDC or S SI)
• o Limited coverage to certain groups oflow income Medicare emollees (qualified Medicare
beneficiaries-QMB)
• Optional Eligibility Groups:
• o many considered optionally eligible are children and pregnant women
• o certain aged, blind, or disabled adults with incomes below FPL but too high to warrant
mandatory Medicaid coverage
• o must provide these beneficiaries with same Medicaid benefits as provided to mandatory
categorically needy
• Georgia Medicaid:
o Covered Services:
•
Doctor/ dentist
•
Cliniclhospital
•
Nursing homelhome health care
•
Family planning/prenatal care
•
Pediatric care
•
Mental health
•
Rx drug coverage
•
Optometrist services/eyeglasses
• o Pharmacy System Outsourced to Express Scripts
o The following are not required to pay a co-payment:
•
Under 21
•
Pregnant women
55
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306 Medication use: Patient demographics Kara Williams
The defintion of the patient includes: healthy persons trying to prevent illness (it is a more
active role than it was in the past) and one who receives medical attention, care or
treatment (there has also been an increase in outpatient care in recent years).
It is predicted that the U.S. population will increase by 27% to 357,452,000 by the year
2025 – with the largest increase being in the 65+ and elderly population (think aging baby
boomers).
The top causes of death in the U.S. are heart disease, cancer and cerebrovascular disease –
this is a shift from the 17, 18 and early 1900’s when the leading causes of death were
dysentery, malaria, smallpox, whooping cough, scarlet fever, etc. The shift was caused
mainly by lifestyle changes i.e. from malnutrition, industrialization, lack of public health,
etc. to diseases of affluence (sedentary lifestyle, poor diet, smoking, etc.)
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306 Medication use: Drug distribution Suvimol Sonchaiwanich

Drug Use Process consists of
o Manufacturing
o Storing
o Distributing
o Prescribing
o Dispensing
o Administering
o Using
o Controlling
o Monitoring
Each step of distribution is highly regulated
o Consumers will either go see a HCP or self-treat
There are 5 categories of drugs
o Prescription
o OTC
o Investigational
o CAM (complimentary or alternative medication)
o Medications dispensed by pharmacists only - in certain countries
Demand of medications driven by consumers, physicians, and patients
o Consumers use of drugs driven by social beliefs, cost, safety, etc.
o Direct to consumer ads influence doctors and patients
o Dispensing is influenced by laws and regulations, managed care and
health insurance
Supply is heavily regulated by FDA
o Approval process, GMP
There are over 1150 manufacturers producing 23,000-29,000 products
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Supply is influenced by
o R&D
o Raw materials production
o Pharmaceutical production/distribution/marketing
Wholesalers provide drugs to pharmacies, hospitals, doctors, nursing homes,
etc.
US is the only market that sells bottles of 500 or 1000; most other countries use
unit dose.
Threats to Drug Use system
o Drug importation
 Illegally bringing in drugs to US
o Counterfeits
 Could have less active ingredients, no active ingredients, or other
harmful substances
Shipping Temperature of Sensitive Products is important
o climate-control vehicles
306 Pharmacy practice: Types of facilities
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o Types of facilities:
 Nursing facilities
 Skilled nursing facilities (SNFs) – work with consultant pharmacists & regulated by
the federal government; most medically & therapeutically intensive of the nursing
facilities
 Acute-affiliated nursing facilities (AANFs) – associated with hospitals
 Hospice care
 Community-based care – falls between institutional LTC and care for ambulatory
patient; not debilitated, can live independently
 Community facility services:
o Adult day care
o Assisted living facilities
o Board and care facilities – mental/physical disabilities, non-medical; shelter,
supervision, personal care services
o Pharmacists geriatric certification (CGP)
 Must meet educational and experimental requirements
 Passed an examination to test knowledge & skills in geriatric pharmaceutical care
 Maintain CE requirement
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306 Pharmacy practice: DRR
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Drug-regimen review
Part of pharmacists activity in LTC setting
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Definition – systemic process to review and assess a patient’s medication therapy and
make recommendations to that patient’s health care provider regarding optimizing the
patient’s medications
Several categories:
o Unnecessary medications/ excessive doses
o Inadequate drug monitoring
o Absence of documented diagnosis or clinical symptoms
o Psychoactive/antipsychotic medication use

306 Pharmacy practice: Pharmaceutical care Lisa Redwin

Pharmaceutical Care – the responsible provision of drug therapy for the purpose of
achieving definite outcomes that improve a patients Quality of Life (QOL)
o Developed by Hepler and Strand in 1990
Evolution of Pharmaceutical Care
o 1970s-1980s
 Health care costs skyrocketed
 Pharmacists seen as businessmen – as an extension to the
pharmaceutical manufacturers
 Clinical Pharmacy as a result – drug use control, and PharmD degree
introduced
o 1980s – 1990s
 Clinical pharmacy criticized for being product driven
 1990 – Hepler and Strand’s Pharmaceutical Care
PC v Clinical Pharmacy
o Clinical
 Seen as a specialized consultant
 In a small amount of practices
 Physician oriented
o PC
 Generalized care in all areas
 Can be done in all practice settings
 Patient Oriented
6 elements of PC:
o Responsible provision of care, direct provision of care, caring, achieving positive
outcomes, improving patients QOL, Resolving medication related problems
(MRPs)
9 steps to PC:
o Develop relationship, collect and analyze information, list the drug related
problems, establish desired therapeutic outcomes, list solutions to MRPs, choose
the best alternative, design a monitoring plan, implement plan, and follow plan.
MTM – Medicare modernization act of 2003 allowed payment for.
Project Destiny – an effort to enhance pharmacies role in patient centered care
o Joint collaboration between APhA, NACDS, NCPA
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306 Pharmacy practice: Pharmacy law Lisa Redwine
·
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*NOTE WE DID NOT COVER THIS IN INTRO 1 – WE COVERED IT IN POP 1*
Georgia’s Definition of Practice of Pharmacy – Interpretation, evaluation, or dispensing
of prescription drug orders in the patient’s best interest
o Participation in drug and device selection, drug administration, drug regimen
reviews, and drug or drug-related research
o Provision of patient counseling and the provision of those acts or services
necessary to provide pharmacy care
Georgia State Board of Pharmacy
o Eight member board, appointed by the governor
o Board meetings 12 times a year – open to the public (but may be closed)
o Duties:
 Regulation of pharmacists and pharmacies in GA
 Enforce Ga’s controlled substances act and maintain list of “dangerous
drugs”
GA’s Narcotics agency
o Law enforcement and regulatory divison of Ga’s state board of pharmacy
o Duties:
 Investigate violations, inspect facilities, educate law enforcement,
information recourse, and compile annual lists of dangerous drugs (Rx
medications)
o Has authority to:
 Conduct inspections of ANY pharmacy at ANY time
 Examine copy or remove pharmacy records
 Examine, copy, or inventory all controlled substances or dangerous drugs
Requirements for licensure:
o NAPLEX – minimum passing score of 75
o MPJE (law exam) – minimum passing score of 75
o GA Practical exams – score of 60% in each section and an overall of 75%
 Offered 2-3 times a year
The RX
o Definition of Rx drug order – a lawful order of a practitioner for a drug or device
for a specific patient
o The 3 rights:
 Patient, medication, and time
The community practice
o Must have a Pharmacist in Charge (PIC)
 Should not be in supervision of more than one pharmacy at a time
o If no pharmacist – no Rx’s will be filled – pharmacy will be closed
 Rx’s may be dropped off
 Pharmacist cannot be absent from pharmacy for more than 3 hours daily
or 1.5 hours at one time.
o All controlled substances must have federal transfer warning on label
o Label is only required IF prescriber checks label on Rx – ONLY IN GA
o
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One pharmacist can only supervise one intern, one extern, and three techs at
any given time. (If one tech is certified – if none – then pharmacist can only
supervise two techs at a time)
o Practitioners must write Rx’s related to their field – exceptions (full prescribing
power):
 Physicians, dentists, veterinarians (animals only), podiatrists (blow the
knee only)
 Limited: Optometrists, Physician’s Assistants, Registered Nurses or
Nurse practitioners
Ga’s controlled substance act
o 1 through 5 (lower the number the more regulated) – class 1 unavailable for sale.
o Refills limited to 6 months from original date of Rx – NO refills for C2s
o For C2’s
 Pharmacists – sign the back of Rx, check the date of issue, ensure serial
number indicated on Rx
o Emergency dispensing:
 Oral authorization form Prescriber, only adequate quantity for emergency,
Rx immediately put into writing, 7 days to receive Rx from prescriber
 Partials ARE NOT PERMITTED
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307 Managed Care: Structure and function of managed care Crystal Ruper:
Managed Care is an organized approach to delivering a comprehensive array of health care
services to a group of enrolled members through efficient management of services needed by
members, and negotiations of prices or payment arrangments with providers.
Functions include:
- Financing
o
Premiums are based on contract negotiations between employer and the managed care
organization.
o
Generally, a fixed premium per enrollee includes all health care services provided for in
one contract.
- Insurance
o
Managed care takes the financial responsibility if total cost of services exceeds revenue
from premiums
- Delivery
o
Managed Care Organizations promise to provide a comprehensive set of services,
including preventive services, ambulatory care, inpatient care, surgery, and rehabilitative
services
--- Ideally MCOs would own and operate their own hospitals and outpatient clinics and employ
their own physicians
--- MCOs establish a network of providers by contracting with physicians, clinics, and hospitals.
o
MCOs using the following payment mechanisms which allow for some degree of risk
sharing:
--- Capitation—provider is payed a fixed monthly sum per enrollee (PMPM)
--- Salaries—often coupled with bonuses or withholdings—provider is an employee of the MCO
--- Discounted Fee—provider is paid according to a pre-negotiated discount schedule (“fee
schedule”)
- 7 Essential Features/Functions of MCOs
o
Cost containment—through practice profiling, choice restrictions, case management,
gatekeeping, etc.
o
Accountability for quality of care
o
Measurement of health outcomes and quality of care
o
Health promotion and disease management programs
o
Management of resource consumption
o
Consumer education programs
o
Continuing quality improvement
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307 Managed Care Medicare Medicaid: Structure and function of managed
care Crystal Ruper
The original Medicare plan is a fee-for service plan. Managed care, known as Medicare Part C
or Medicare Advantage plans, gives those on Medicare the option of enrolling in one of the
approved HMOs. The patient continues to pay premiums to Medicare and will also pay
premiums to the Managed Care organization.
¾ Eligibility: If you are entitled to Part A or enrolled in Part B, you may elect to enroll in
Medicare part C.
¾ Enrollment in part C plans has been declining
Managed Care has been much more successful in Medicaid than in Medicare. Nationwide,
about 61% of patients enrolled in Medicaid receive care through private Managed Care. In
Georgia, 75% of Medicaid recipients are enrolled in Managed Care through Care Management
Organizations. 25% of Medicaid recipients in Georgia are enrolled in the traditional fee for
service plans.
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307 Managed Care: Medicare Medicaid Kelly McAtee
Focus on Medicare (Medicaid is below):
Part A: for hospitalizations, home health, hospice.
Part B: supplementary medical insurance, physician, outpatient, preventative services.
Part C: Medicare Advantage program, private plan option.
Part D: prescription drug benefit.
-To be eligible for Medicare must have paid payroll taxes for the past 10+ years.
-Control drug cost by using: formularies, tiered pricing, step therapy, prior authorizations, and
preferred drug lists.
-Groups of drugs with NO restrictions: antidepressants, antipsychotics, chemotherapy drugs,
immunosuppresants, HIV drugs, antiepileptics.
-Exclusions include: OTC medications, benzodiazepines, barbiturates, weight loss/gain
products, fertility drugs, Rx vitamins and minerals.
- Additional info about Part C: expanded set of options for delivery of health care services
including PPO’s and other manged care organizations.
-Benefit of managed care: if the plan costs lower than Medicare payments, cost savings are
required to be passed along to the person or returned back to Medicare.
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307 Managed Care: Medicare Medicaid Kelly McAtee
Focus on Medicaid (Medicare is above):
3 major groups are covered by Medicaid1) individuals who receive cash assistance through SSI
2)pregnant women and children under 6 below certain income limits and all children under 19 in
families below the poverty level
3) Low income Medicare enrollees.
-Medicaid is not required by states, but all states do have a Medicaid program. States must
adhere to 3 requirements: Statewideness, freedom of choice and comparability of service. 61%
of Medicaid patients are enrolled in managed care (more successful than Medicare).
-Federal and state governments share financing and administration.
-Drug plans are optional for each state to be covered on Medicaid.
-The most someone can pay for a Rx drug on Medicaid is $3.
-Georgia has about 59 million people on Medicaid. 50% are children.
-Mail order pharmacies, internet pharmacies and out of state pharmacies are excluded from
Medicaid.
-Medicaid reimburses pharmacies that are for profit: AWP- 11% + $4.63 (dispensing fee) and
not for profit pharmacies: Acquisition cost + $4.33 (dispensing fee).
-The most Favored Nation Rate (MFN)= lowest agreed reimbursement for any other commercial
payer submitted to Medicaid.
-In Georgia, 75% of people are in care management organizations (CMOs) and 25% are
enrolled in Fee-for-Service (FFS).
-Covered products include: drugs with rebates, preferred drug list, prior authorizations, and
quantity level limits.
-States may have recipients contribute to the cost of their health care: by deductibles, co-pays,
or co-insurance.

307 Health benefits and drug approval process: Epidemiology Rebecka
Hazelwood
Clinical Pharmacology: Study of the effects of drugs in humans
Epidemiology: Study of the distribution and determinants of disease and health in populations
Pharmacoepidemiology: Study of the use and effects of drugs in large numbers of people
Measures of Disease Frequency
Proportion:
Relation of parts or elements within a whole
Reported as fractions, decimals, percentages
No units
Ex: Proportion of population with hypertension
Rates:
Ratio that compares two different kinds of numbers
Numerator (count data) and denominator (usually time) have
different units
Ex: Infusion rate of 100 mL/hour
Incidence:
Cumulative Incidence:
# New cases in population at risk over a specified period of time/# Persons at
risk for developing the condition over a specified period of time
Incidence Density:
# New cases in population at risk over a specified period of time/Total
person-time of observation
Prevalence:
# Cases of disease/outcome at a specified time/# people in population at a
specified time
Measures of Association
Outcome
Exposure
+
-
+
A
b
-
C
d
Relative Risk (RR ):
(a/(a+b))/(c/(c+d))
Interpretation: - 1.0 (null value): no elevated/decreased risk.
- 1.67: you have a 67% increased risk of having the outcome if you took
drug A vs drug B.
Attributable Risk (AR):
a/(a+b)-c/(c+d)
Interpretation: - 0.0 (null value): no cases can be attributed to drug A.
- 0.13: 13 of 100 cases can be attributed to drug A.
Odds Ratio (OR ):
(a/c)/(b/d)
Interpretation:-1.0 (null value): people with the condition are no more likely to have taken drug A
than people without the condition.
-2.0: people with the condition were two times more likely to have taken drug than
people without the condition.
Study Designs
Experimental: Intervention
Quasi-experimental: Cohort (select subjects based on +/- exposure); follows subjects forward in
time
Case Control (retrospective)
Nonexperimental:
Cross Sectional(snapshot study)
Correlational (comparing factors in populations)
Case Series (group of patients)
Case Report (single patient)
Confounding variables: Variables that can damage the internal validity of an experiment
Controlling confounding:
Design: Randomize, restrict, match
Analysis: Stratify (based on age, race, sex, etc), multivariate analysis
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307 Health benefits and drug approval process: Health insurance Rebecka
Hazelwood
Purpose of insurance: to reduce pure risk.
Pure risk: possibility of loss but no gain (eg. illness and natural disasters)
Speculative risk: chance of gain as well as loss (eg. gambling)
Premiums are based on the claims experience of the policyholders who make up the risk
pool.
The uninsured
~45 million Americans (15%)
Working poor is the largest group of uninsured adults
Evolution of the Health Insurance Industry
Began with federal Marine Hospital Service in 1798
§ Disability insurance (emphasis on protecting income)
During the Depression, hospital insurance became attractive
§ Blue Cross 1929
Medical insurance
§ Blue Shield 1939
Health insurance benefits became an important part of labor negotiations during
WWII
Indemnity vs Service Benefit Insurance
Indemnity: reimburse patient for a portion of medical expenses
Service Benefit: health care providers are paid directly by the insurance plan
Fee-for-service basis: providers receive a fee for each service performed
Evolution of Prepaid Prescription Drug Programs
Labor unions major catalyst in growth of prepaid prescription plans
Structure of the Health Insurance Industry
Cost sharing – 3 forms:
§ Copayment (patient pays specified dollar amount)
§ Deductible (patient pays 100% out-of pocket up to a certain amount before
plan kicks in)
§ Coinsurance (patients pays % of service)
Actuarial Analysis:
§ Estimating the amount of risk assumed by an insurance company
§ Estimates the income (premiums) that must be earned to cover the
estimated expenses (cost per member per month, PMPM)
Prescription Coverage: Exception to Risk Management Principles
Cost of a prescription does not represent a substantial loss
-
Some medications (eg. oral contraceptives) do not represent an accidental or
unpredictable hazard
Administrative costs are high
Potential Risk Management Problems
Catastrophic Hazard: no coverage for widespread, catastrophic events (eg. war &
earthquakes)
Adverse Selection: purchasing insurance due to expecting a loss
Incentives to Create Losses: gaining from an apparent loss (eg. insuring a car for more
than its value)
Patient-Induced Demand: health insurance has encouraged patients to use services
more than ever (by decreasing out-of-pocket expenses)
Strategies for Avoiding Risk Management Problems
Group policies
Coverage limitations
Coordination of benefits
§ Health insurance policies usually pay after auto, homeowner’s, or workers’
compensation have paid their portion
Pharmacy Benefit Manager (PBM)
Contracts with pharmacies (process claims, reimburse, auditing, etc)
Maintaining formulary systems
Conducting drug utilization review (DUR)
Controlling costs and utilization
Reimbursement – 3 parts:
Cost of drug (% discount of average wholesale price – AWP)
Dispensing fee
Patient cost sharing
§ Tiered copayment: Low copayment for generics, higher for preferred
brand-name drugs, and even higher for non-preferred brand-name.
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307 Health benefits and drug approval process: Drug approval process
Chris Shumans
Overview
•Drug Discovery
•Pre-Clinical R&D
· GLP- good laboratory practice
· In vitro and in vivo
· Pharmacological studies- toxicity, carcinogenicity, mutagenicity,
tetragenicity
· Toxicity- acute in two specicies, short-tern toxicity 2wks-3mon
· Animal testing- requires approval of ethics committee
•Investigational New Drug (IND) Submission
· Pre-IND (FDA/Sponsor meetings)- Opportunity to agree on design of
animal studies, discuss data requirements, etc.
·
·
·
IND must be filed prior to testing in humans and provides details
about the proposed clinical trials and information about the drug
substance
FDA has 30 days to review IND data
Types of INDs
•Commercial IND
o Permits collection of safety and efficacy data in order for the
drug to be potentially marketed
o (I.E. Treatment IND)
•Non-Commercial IND
o Permits use of a drug in order to advance scientific knowledge,
not potential marketing
•Clinical Trials – Phase I, II, III
· Institutional Review Board –Ensure the welfare and rights of people
participating in clinical trials and ensure patients have given written consent
before the study begins
· Regulatory Requirements:
o GCP- good clinical practice
o FDA 21 CFR
o International Conference on Harmonization (ICH)
· Phase I- safety and PK data
o (n15-100; single site)
o Introduction in (healthy) human subjects
o Assess afety and pharma
· Phase II- drug safety and dose-ranging
o (n100-300; 2-80 sites)
o First trial for targeted population with condition
o Determines safety and efficacy
o Determines therapeutic dosage
o Generally double-blind, randomized, controlled studies from months
to years
· Phase III- confirm drug safety and efficacy- multi-site trial
o (n=1k-5k; 10-100 sites)
o Prior to phase III, must have FDA meeting and determine if safe to
proceed
o 3-5 years, at least two trials required
•New Drug Application (NDA) Submission and Review
· Phases I, II, III data needed for submission, manufacturing data, packaging,
labeling, etc
· •Review Teams
o Medical Officers, Statisticians, Chemists, Biologists, Pharmacologists,
and Other
o Advisory Committee (panel of external experts)
o Target Review Times: Standard= 12 mo.s; Priority = 6 mo.s
o PDUFA fees- ‘08= 1.1 mil for app w/clinical data
Post-Marketing Activities· Clinical Phase IV- post marketing sureillance
§ Long term safety
§ Broaden indications/uses/dose regimen
· Market exclusivity· Over 8 yrs in70’s to under 2 yrs by 98’
· GMP- good marketing practice
§ Inspections- biennial surveillance, compliance “for cause”
•Costs
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Development costs in 70-80 $138 mil
Development costs in 80-90 $318 mil
Development costs in 90-00 $802 mil
o Pre-clinical- 207 mil; 3-6 yrs
o Clinical trials- 345 mil; 6-7 yrs
o FDA review/Manufacturing- ½-2 ys $73.8/$105.9 mil
307 Health benefits and drug approval process:Pharmacy benefit Chris
Shumans
What Do Pharmacy Benefit Managers Do?
 Manage formularies
1) decide what drugs to cover
2) decide what tier a drug belongs to
3) decide what drugs require Prior Authorization or Step Therapy
4) decide maximum dispensing limits (MDL)
5) decide on how new drugs coming to market will be treated
 Contract with pharmaceutical manufacturers
 Offer health and wellness programs
 Disease management
 Health risk assessments
 Smoking cessation
 Pharmacy & Therapeutics Committee (P&T)
 Usually comprised of physicians and pharmacists
 Meets often to review newly available drug therapies and treatment options
 Responsible for clinical composition of formularies
 Clinical content decisions based on:
 Efficacy
 Safety
 Off Label Uses
 Pharmacokinetics
 Role in therapy
 Indications
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 Outcomes Research
 Operations
 Operations has to do with the actual service of a pharmacy
 Most PBMs own their own call center and/or mail service
 Opportunities for pharmacists to have direct contact to members from a PBM
perspective
 Call Centers
 Pharmacists can help explain benefits to members/providers as well as
formulary questions
 Discuss reasons for UM and why a drug needs to be monitored or controlled
 Drug Information questions that come from various employer groups/clients
 Mail Order
 PBMs need pharmacists to dispense drugs within their mail order pharmacies
 Pharmacists not only dispense medications within the mail order service, but
also help to improve processes
 Mail Order pharmacies dispense up to 10,000 Rx’s per day and process
improvement/efficiency is a key part of profitability for the mail order pharmacy
 Corporate PBM
 Account management – consultative, day-to-day management of clinical
offerings to client base
 Clinical program development – create and manage utilization management
programs before they are implemented and managed by pharmacists
 Drug Information – provide internal and external customers with pertinent drug
data
 Rebate Management – contracting with manufacturers
 Network Management – support network design and contracting
 Specialty Products – management of high cost, high touch product offering
 Informatics – support client reporting and complex database analysis
 Product development – ongoing support to variety of client offerings, both
internally and externally
 Marketing – support corporate initiatives to promote the organization
 Outcomes – support pharmacoeconomic analysis
Who Do Pharmacy Benefit Managers Serve?
•Corporate health plans
•Health plan organizations
•Insurance groups
•Blue Cross Blue Shield plans
•Government entities (federal, state, local)
•Taft Hartley/unions
•Third-party administrators
•Discount card/cash card programs
•Medicare Part D individuals
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320 Introduction to Biochemicals: Amino Acids and Proteins Thien-tu
Nguyen
Amino Acids and proteins:
Amino acids make up peptides and proteins. They have an amino and carboxyl end.
They
are joined by peptide bonds. Proteins will fold up based on their functional groups. The way the
protein is folded defines its functions and abilities. Amino acids come in two forms, D and L.
Eukaryotes use the L form. Peptides are polymers of 2-100 amino acids, proteins are larger.
The peptide bond is rigid and planar.
Proteins function:
1.
2.
3.
4.
5.
6.
7.
8.
Catalyses
Structure
Movement
Defense
Regulation
Transport
Storage
Stress Response
Fibrous proteins are long stranded molecules, for example collagen. Globular proteins
have spherical shapes; most enzymes are globular, example: myoglobin.
Four levels of protein structure:
1. Primary, the amino acid sequence
2. Secondary, the 3d arrangement of the backbone atoms in space, which are alphahelices, and beta-pleated sheets.
3. Tertiary, the 3d arrangement of all the atoms in space
4. Quaternary, more than one polypeptide chain is joined together.
Denaturation can be reversible or irreversible; it is the loss of protein structure. Denaturing
destroys the physiological function of the protein.
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320 Introduction to Biochemicals: Carbohydrates Thien-tu Nguyen
Carbohydrates:
Monosaccharides make carbohydrates. You can have different arrangements of hydroxyl
groups around the chiral carbons. There are aldoses and ketoses. Monosaccharides can have
3-6 carbons. The last chiral carbon (next to the last carbon) is used to name the sugar, as a D
or an L. All sugars in nature are D isomers. Most simple sugars of 4 or more carbons exist in
the cyclic form; it is named alpha or beta based on the carbonyl carbon (anomeric). In alpha the
OH group is on the bottom, and in the beta the OH group is on top. Isomerization can occur, for
example an aldehyde can go to a ketone. You can join MS by glycositic links to form DS. PS
are stored as starch in plants, for example, amylose. Glycogen is a storage CHO in animals.
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320 Introduction of Biochemicals: Lipids Linh Cao
Lipid classes:
1.
2.
3.
4.
5.
6.
Triacylglycerols- fats and oils.: storage, insulation, in adipocytes
Wax esters : in skin of plant and animal fur
Phospholipids: 2 types Phosphoglycerides and sphingomyelins
Fatty acids and their derivatives
Sphingolipids
Isoprenoids
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Long chain lipids are hydrophobic, short chain lipids are amphipathic.
Unsaturated fatty acids have one or more C-C double bonds, and can be in cis or trans
formation.
Phospholipids have both hydrophobic and hydrophilic ends.
Sphingolipids are common in the nervous system. Tay sachs disease
Isoprenoids contain a repeating 5 C unit known as isoprene, and they form hormones.
Con sist of terpenes ( in vitamin K and vitamin E) and steroids (sex hormone and
cholesterol)
Membrane lipids help maintain appropriate fluidity. They are selectively permeable, selfsealing capacity, and are asymmetric. Proteins are integrated into the membrane.
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320 Introduction to Biochemicals: Nucleotides Linh Cao
1. Nucleotides:
-
Contain a 5-C sugar, a nitrogenous base, and one or more phosphate groups.
-
Nucleotides bases are either pyrimidines or purines.
The sugar is either deoxyribose (DNA) or ribose (RNA).
Purines are adenine and guanine.
Pyrimidines are cytosine, thymine, or uracil.
Nucleotides are building blocks of nucleic acids.
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320 General Properties of Enzymes: Nomenclature Leslie Harris
-Enzymes have a conventional name which usually adds the suffix –ase to the name of the substrate
(Ex: Urease)
-Official enzyme names come from the International Union of Biochemistry (IUB) and include:
-4 Digit number classification, A systematic name according to the catalyzed reaction, and a
recommended name.
Ex: alcohol:NAD+ oxidoreductase
Substrate, Coenzyme, Enzyme
EC 1.1.1.1
alcohol dehydrogenase- Conventional name
6 Classes of Enzymes
EC1. Oxidoreductases catalyze redox reactions. Ex: reductases, dehydrogenases.
CLUE: If co-enzyme is involved.
EC2. Transferases- Transfer molecular groups from one molecule to another. Ex:
Kinases, transaminases, transcarboxylases.
EC3. Hydrolases- cleave bonds by hydrolysis. Ex: Phosphatases, proteases,
esterases. CLUE: will require addition of water.
EC4. Lyases- catalyze removal of groups to form double bonds or addition of groups to
double bonds. Ex: decarboxylases, anyhydrases. CLUE: Can involve removal of water
to form a double bond.
EC5. Isomerases- catalyze intra-molecular rearrangements. Ex: mutase.
EC6. Ligases- join (ligate) 2 molecules at the expense of ATP hydrolysis. Ex:
carboxylase. CLUE: 2 groups become 1, ALWAYS involves ATP.
**Apoenzyme- enzyme without co-factor, Holoenzyme is catalytically active enzyme
Apoenzyme + Cofactor = Holoenzyme
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320 General Properties of Enzymes: Enzyme Kinetics Leslie Harris
Enzyme Kinetics
-Studies the rate of an enzyme-catalyzed reaction. Rate= change in the concentration of reactant per
unit time.
-First-Order Kinetics occurs when there is 1 molecule of substrate. It is synonymous with Linear Kinetics.
Straight line when graphed.
Vo= k[A]
The slope of the line will equal k- the rate constant.
-Second-Order Kinetics occurs when 2 different substrates. It is hyperbolic.
Vo= k[A] [B]
-Pseudo First-Order occurs when [water] >>>>[A], Water remains constant. Ex: hydrolysis reactions
Vo=k[A]
-Zero- order kinetics- velocity is independent of concentration. Graphed as straight, horizontal line.
Vo=k
-Michaelis-Menton Kinetics
-Valid only when [P] is low, during initial reaction period
*we were told to not memorize the equation, so I assume it will be given to us.
-Km is the Michaelis constant
-Vmax occurs when enzyme is saturated with substrate
-Initially: First order because [S] <<Km
-Becomes zero-order when [S]>>Km (very end of reaction)
-Turnover number: the number of substrate molecules converted into product by an enzyme in a unit
time when the enzyme is fully saturated with substrate. Aka Catalytic rate constant- t2
-kcat/Km indicates the efficiency of an enzyme. Maximum possible is 108-109. This would be a “perfect
enzyme”
-Lineweaver-Burk Plot
-gives direct and more accurate measures of Vmax and Km.
-Allosteric Enzymes
-Do NOT conform to Michaelis-Menton Kinetics because velocity change is faster and are too complex
(tend to be quaternary structures with multiple active sites). Gives sigmoidal graph.
-regulate the flux of biochemical through metabolic pathways. Activity is regulated by environmental
signals.
-ALWAYS catalyze the committed step of metabolic pathways
-Feedback inhibition is common for biochem regulation
-Concerted Model (MWC model)- 2 distinct conformations: T state(tense): inactive, low affinity. R
state(Relaxed): active, high affinity. All of the active sites will be in the same state- “all or none”.
Substrate binds more readily to the R form which will shift the equilibrium in favor of R (cooperativity).
-Heterotrophic effects on Concerted Model: signal molecules bind to regulatory site (distinct from active
site) and alter T and R equilibrium. Positive Effectors stabilize the R state, lower threshold and promote
R-S binding. Negative effectors stabilize the T state, raise the threshold, and decrease R-S binding.
-Homotropic effects refer to the effect of substrates on allosteric enzymes (sigmoidal kinetics)
-Sequential Model- Binding of substrate changes conformation in one subunit which then induces
changes in neighboring subunits. As more subunits change to R state- higher affinity for substrate
-Loss of allosteric control causes gout by loss of feedback inhibition.
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320 General Properties of Enzymes: Regulation of Kinetics Whitney Blan
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Inhibitors interfere with enzyme action.
o They may be reversible or not.
Three kinds of reversible inhibitors are:
o competitive - which mimics the substrate and binds to the enzyme at the
active site
o uncompetitive - which binds only to the enzyme substrate complex
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o
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noncompetitive - does not look like substrate and binds at a site other
than the active site.
Irreversible binding denatures a protein.
Catalytic mechanisms facilitate ligand-receptor binding.
 Metal cofactors and coenzymes can be used to facilitate this.
Excessive temp. and unoptimal pH can denature proteins.
Some mechanisms that organisms use to regulate enzyme activity are:
 genetic control
 covalent modification
 allosteric regulation
 compartmentalation.
320 Vitamins and Coenzymes: Compositions/Structure Krystal Avula
Many enzymes require cofactors for activity
apoenzyme = an enzyme without it’s cofactor
haloenzyme = catalytically active enzyme
Cofactors execute chemical reactions that can not be performed by the standard set of
20 amino acids
Cofactors can be subdivided into 2 categories
metals (metal ions)
co-enzymes (small organic or organometallic molecules)
********Most coenzymes are derived from Vitamins (especially Vit Bs)********
Coenzymes
Organic molecules that facilitate enzymatic catalysis
Bind to active sites of enzymes by:
reversible, weak, and noncovalent interactions, or
covalent bonds or strong noncovalent interactions
prosthetic groups
Undergo structural changes during catalysis, must be regenerated before another
catalytic cycle
Enzymes that use the same coenzyme usually perform catalysis by similar mechanisms
Ex. many oxidoreductases require NAD+/NADH and NADP+/NADPH to assist in
electron transfer
Table 14.3 The B vitamins
Vitamin
Coenzyme
Thiamine (B1)
TTP
Riboflavin (B2)
FAD or FMN
Pyridoxine (B6)
Pyridoxal phosphate
Nicotinic acid (niacin) (B3) NAD+ or NADP+
Pantothenic acid (B5)
CoA
Biotin (B7)
Biotin-lysine adducts (biocytin)
Folic acid (B9)
THF
B12 Cobalamin
5’-Deoxyadenosyl cobalamin
NAD+ and NADP+ Participate in Redox Reactions B ex. NAD+ (ox’d) -->NADH (reduced)
The nicotimamide part of NAD+ (or NADP+) accepts a hydride (H plus 2 electrons) from
the substrate
The substrate loses a proton to the solvent
FAD and FMN Participate in Redox Reactions ex. FAD --> FADH2
CoA Participates in Acyl Group Transfer - key for pyruvate dehydrogenase (link
between glycolysis and krebs cycle)
320 Vitamins and Coenzymes: Classification Water Soluble Enymes Krystal Avula
Vitamins “vital amines”
Essential for human growth and development
Acquired from diet
2 types: water-soluble and lipid-soluble
Water-soluble (vitamins B, C, Choline)
Mostly precursors of co-enzymes (especially Vit Bs)
Excessive levels are excreted in urine
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320 Vitamins and Coenzymes: Classification Fat Soluble Vitamins Leah
Collins
Coenzyme: organic molecules that provide enzymes with chemical versatility because
they possess reactive groups not found on amino acid side chains or can act as carriers
for substrate molecule
most coenzymes are derived from vitamins
fat soluble vitamin
coenzyme form
Rxn/process promoted
vitamin A
Retinal
vision, growth, reproduction
vitamin D
1,25-dihydroxycholecalciferol
calcium/phosphate metabolism
vitamin E
unknown
lipid antioxidant
vitamin K
unknown
blood clotting
Fat soluble vitamins are stored in the liver and fatty tissue, and are eliminated much
more slowly than water-soluble vitamins → can lead to toxicity if too much is
accumulated
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320 Metabolism/Energy Utilization: Carbohydrates - Synthesis/Metabolism
Warner Wolf
Metabolism of carbohydrates: glycolysis
Glucose + 2Pi + 2ADP + 2NAD+ → 2 pyruvate + 2ATP + 2NADH + 2H+ + 2H2O
Pyruvates are then converted to acetyl CoA by enzyme pyruvate dehydrogenase (PDH) to enter
Krebs cycle (aka TCA cycle & citric acid cycle) --> produces 3 NADH (2.5 ATP each) and 1
FADH2 (1.5 ATP) to be utilized by ETC
Synthesis: gluconeogenesis = forming new glucose molecules from precursors in liver
§ liver responding to extracellular signals from PFK-2
§ precursors: lactate, pyruvate, alpha-keto acids and glycerol
§ controlled by substrate availability, allosteric effectors, and hormones
§ cori cycle – lactate in muscle travels to liver, converted to pyruvate --> glucose
§ alanine cycle – pyruvate in muscle --> alanine, carried to liver (pyruvate cannot be
transported) and reconverted to pyruvate
o
also transfers ammonium to liver for excretion
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320 Metabolism/Energy Utilization: Carbohydrates - Key Steps Warner Wolf
Glycolysis: 3 key steps, Magnesium is a co-factor in all of them
1. Hexokinase: the gateway regulator, inhibited by it’s own product (allosterically) – G6P,
activated by glucose
2. Phosphofructokinase: COMMITTED STEP (main regulator of glycolysis), converts F6P to
F-1,6-BP; inhibited by high concentration ATP, citrate, & H+ ions… activated by F-2,6-BP
3. Pyruvate kinase: activated by F-1,6-BP – inhibited by ATP, lactate and alanine
Citric Acid Cycle: 2 & 3 (below) are oxidative decarboxylation reactions (CO2 is product), also
produce NADH… both are inhibited by high energy charge (ATP/NADH)
1. Citrate synthase: inhibited allosterically by citrate, by ATP and succinyl CoA
2. Isocitrate dehydrogenase
3. Alpha-ketoglutarate dehydrogenase: very similar to PDH, inhibited allosterically by succinyl
CoA, stimulated by AMP & NAD+
Gluconeogenesis: must bypass 3 irreversible reactions of glycolysis
1. Pyruvate converted to OAA by pyruvate carboxylase in mitochondira, exported outside and
converted to PEP by enzyme pyruvate carboxykinase
2. Fructose-1,6-bisphosphatase converts F-1,6-BP to F6P
3. Glucose-6-phosphatase converts G6P to glucose in liver
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320 Metabolism/Energy Utilization: Carbohydrates – ETS Alex Juggassar
o
·
The Electron Transport Chain (ETC) is a series of electron carriers in
order of
increasing electron affinity.
o
o
o
o
o
o
o
o
o
o
o
o
o
o
o
o
o
o
o
o
o
o
o
o
o
o
o
o
o
o
·
Most components of the electron transport chain (ETC) are located in four
complexes
·
Complex I: NADH Dehydrognase (enzyme) NADH + H+ + UQ à
NAD+ + UQH2
·
NAD+ can go to TCA cycle and give electrons to ubiquinone
·
Highly excergonic reaction (negative delta G). Energy released is used to
synthesize ATP (NOT S-L-P, called Oxidative Phosphorylation. Key: Complex
Pumps H+.
·
Complex II: Succinate dehydrogenase complex - overall: succinate + UQ
à
fumarate + UQH2.
·
Succinate is the reducing agent… Fumerate is the molecule that is
formed after succinate is reducted. Gets electrons using FADH2 into chain
·
Complex III: UQH2+ 2 cyt c[Fe(III)] à UQ + 2 cyt c[Fe(II)] + 2 H+
·
Ultimate result is 2 cytochrome C’s and 2 H+’s .
·
Cytochromes are proteins with a heme-prosthetic group.
·
Electrons change oxidation
state of heme iron reduced Fe2+,
·
oxidized Fe3+.
·
Complex IV: Cytochrome oxidase: 2 cyt cred + 2 H+ + 1/2 O2 à 2 cyt
cox + H2O.
· Take reduced cytC and react it w/ oxygen and 2 H+ to get water. Reaction is
strongly exothermic. Free’s a lot of energy when take electrons from cyt C.
·
b. inhibitors
Respiratory inhibiters block electron flow in the ETC, shutting off oxidative
phosphorylation.
Work by binding to components in ETC and as a result you sufficate because
can’t use O2. Which is most potent poison and WHY?? Antimycin A is most
potent…because it blocks all electrons flow (like cutting a copper wire in half).
Further down you go the less opportunities for organism to try and fix the
problem.
Oxidative phosphorylation
·
Some energy from oxidation in the ETC is used to phosphorylate ADP to
ATP.
·
Reactions in the ETC pump protons from the matrix to the intermembrane space.
·
This results in an electrochemical potential with a high + charge in the
inter-membrane space versus in the matrix.
·
A protein complex called ATP synthase couples oxidation to
phosphorylation.
·
Activated when ADP (respiratory control) and [Pi ] are high
·
Inhibited when [ATP] is high
·
a. Chemiosmotic theory
·
As electrons pass through the ETC, protons are transported to the
intermembrane space. An electrical potential, y, and proton gradient, DH,
develop.
·
These excess protons pass through the inner membrane back to the
matrix via special channels which contain ATP synthase activity.
·
b. ATP synthesis
·
Drop in [ATP] in cytoplasm à more ATP synthesis because product is
removed so reaction will be driven forward. More ATP at the expense of H+
o
o
o
o
o
o
o
o
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gradient and electron transfer. Synthesis will require more substrate’s to get [O]
to pump the H+ gradient back up.
·
Is a system for pumping H+… high [H+] outside, low on the inside, every
time a H+ is pumped out you decrease the CHARGE of the MATRIX and
increase it outside the membrane. ADP and inorganic PO4 are used to make
ATP. Electron energy is used to make a proton gradient which is coupled to ATP
synthesis, inside the inner mitochondrial membrane.
·
5. Uncouplers of oxidative phosphorylation
·
Uncouplers do not affect the electron transport chain. They prevent ATP
formation by disrupting the proton gradient. Eg:
·
2,4-dinitrophenol is a base under physiological conditions. It neutralizes
protons in the intermembrane space.
·
Antibiotic uncouplers, such as gramicidin, work by providing protein
channels through the inner mitochondrial membrane. Protons can return to the
matrix without going through the ATP synthase. Thus no ATP is synthesized.
·
Mitochondria disperse most of the energy from the ETC as heat, not ATP
molecules.
·
About 10% of the protein in the membrane of the mitochondria is
uncoupling protein (UCP) or thermogenin.
·
Nonshivering thermogenesis is regulated by norepinephrine.
320 Metabolism/Energy Utilization: Lipids Olia Murray
Fats in the stomach à triglycerides in adipose tissue:
Large droplets of dietary fat (each is a molecule of glycerol with 3 fatty acids attached =
triglyceride = triacylglycerol) enter the lumen of small intestine and get broken down into small
micelles by bile salts. (Micelles - small droplets of fat covered by bile acids) Next, lipases
(pancreatic enzymes) break down micelles into these products: 2 fatty acids + one 2monoglyceride. (Purpose: make them small enough for absorption.) The products are absorbed
into the mucosal cells of small intestine and converted back to triglycerides there. After that
triglycerides are combined with cholesterol and protein to form chylomicrons. Chylomicrons are
too large to go into capillaries => they are shuttled into the lymphatic system through lacteals.
From here they will eventually go into the systemic circulation. As they travel through systemic
circulation they will be taken up and by adipocytes (fat cells) in peripheral tissues. (The fatty
acids our body obtains from food are stored primarily as triglycerides in adipocytes! That’s the
major source of fatty acids for synthesis of other molecules or energy production.)
Fatty acids are further processed in 3 stages.
Stage 1: Lipolysis (in adipose cells)
This is the process of mobilizing (freeing, cleaving) of fatty acids from triglycerides in
adipocytes. In the process triglycerides are hydrolyzed to 3 fatty acids and glycerol, which are
released from adipose tissue. Fatty acids are transported with the help of albumen (plasma
protein; fatty acids cannot travel by themselves!) to energy requiring tissues and glycerol can be
utilized by the liver. In the liver glycerol will undergo subsequent phosphorylation, oxidation,
and isomerization to form D-glyceraldehyde-3-phosphate, which is a common intermediate for
both glycolysis and glyconeogenesis => can be shuttled in either direction. Hence, depending on
energy requirement glycerol can eventually be converted either to pyruvate (through glycolysis)
or to glucose (through gluconeogenesis).
Stage 2: Activation of Fatty Acids (in the cytoplasm of a cell in energy-requiring tissue)
Fatty acid needs to be activated so it can begin the metabolic pathway (ß-oxidation pathway).
The process of activation occurs in the cytoplasm, uses 2 molecules of ATP and results in the
formation of acyl CoA thioester. The thioester is then transported to mitochondria matrix across
the inner mitochondrial membrane in the form of acyl carnitine ester. Once in the matrix, acyl
carnitine is converted back to acyl CoA thioester, which proceeds to ß-oxidation. Carnitine
(alcohol) is transported back into the cytoplasm, so it can repeat the cycle.
Stage 3: ß-oxidation (in the mitochondrial matrix)
ß-oxidation occurs in 4 steps, which comprise 1 cycle:
Step 1: oxidation (of acyl CoA thioester!)
Step 2: hydration
Step 3: oxidation
Step 4: thiolysis
Through each cycle we’re removing 2 carbons from the fatty acid in the form of Acetyl CoA.
The number of cycles the fatty acid will go through depends on how many carbons there’re in
the fatty acid chain. Ex. 16 carbons => 7 cycles (each cycle removes 2 carbons (in the form of
Acetyl CoA); the last cycle produces 2 acetyl CoA molecules!) => 8 Acetyl CoA produced.
Through each cycle we generate: 1 FADH2, 1 NADH, 1 Acetyl CoA
(2 Acetyl CoA in the last cycle though!!)
These products eventually generate ATP:
1 FADH2 – 1.5 ATP (through oxidative-phosphorylation; FADH2 is shuttled to ETC)
1 NADH – 2.5 ATP (through oxidative-phosphorylation; NADH is also shuttled to ETC)
1 Acetyl CoA – 10 ATP (Acetyl CoA is shuttled to the Krebs cycle)
Now back to the example I gave earlier: fatty acid contains 16 carbons => 7 cycles => this fatty
acid produces 108 ATP
(7x1.5=10.5, 7x2.5=17.5, 8x10=80, and 10.5+17.5+80=108)
However, the net result will be only 106 ATP because 2 ATP were used during activation of
fatty acid to produce thioester (in stage 2).
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320 Metabolism/Energy Utilization: Lipids Olia Murray: Look above, same.
320 Metabolism/Energy Utilization: Amino Acids
Food enters the stomach: Parietal cells release HCL and chief cells secrete pepsinogen.
Other zymogens are released from the pancreas and cleave proteins into di and tri peptides
and amino acids. Amino acids are absorbed into the intestinal lumen and then into the
blood. Amino groups can be removed by transaminases and glutamate dehydrogenase,
many require pyridoxal phosphate. Glutamate dehydrogenase and PLP function in
forming ammonium excreted in urine or converted to urea which is secreted in urine.
Glutamine shuttle and glucose alanine cycle are both used in forming/excreting urea.
Blood Urea Nitrogen- when elevated can show renal dysfunction.
Amino Acids can be catabolized using the TCA cycle. They can also be used to form
pyruvate or lipid metabolism. Glucogenic Amino acids are converted to glucose during
starvation. Ketogenic amino acids are converted to keto bodies during starvation.
Precursors of Amino Acids:
Glutamic acid àGABA
Histidine à Histamine
Tryptophan à Serotonin
Methionine is important for the methyl folate trap when there is a deficiency in Vit. B12.
Phenylalanine à Tyrosine
A deficiency in Phenylalanine hydrogenase will lead to PKU. PPA will be produced and
is toxic to brain cells, leading to mental retardation and death.
Tyrosine à Dopamine à Norepinephrine à Epinephrine
Thyroid hormones are produced from tyrosine, in thyroid follicular cells.
Creatine kinase (AST) is used for diagnosis of MI.
Serum creatinine is used to evaluate kidney function, using creatinine clearance.
Porphyrins are used to create heme. If this process is blocked you can have neurological
symptoms and photosensitivity. Degradation of Hb, Hb goes to heme, and then bilirubin,
forms water soluble conjugate that is bilirubin albumin, travels to the liver where bilirubin
is released and turned in to BDG, BDG travels to the colon where bacteria change it to UB
and is excreted in feces. In normal livers, there is barely any urine UB, there is no bilirubin
in the urine, and there is fecal UB. In the case of pre-hepatic blockage fecal UB is
increased and urine UB is increased and bilirubin is absent in the urine. For hepatic
blockage (cirrhosis), urine UB is increased, urine bilirubin is present, and fecal UB is
decreased. Post hepatic (obstruction) urine UB is absent, bilirubin present in urine, and
fecal UB is trace to absent.
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320 Molecular Biology: Nucleic Acids Rozita Tebyanian
Nucleotides: Contain a 5-C sugar, a nitrogenous base, and one or more
phosphate groups. Nucleotides bases are either pyrimidines or purines.
The sugar is either deoxyribose or ribose. Purines are adenine and
guanine. Pyrimidines are cytosine, thymine, or uracil. Nucleotides are
building blocks of nucleic acids (DNA, RNA).
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320 Molecular Biology: DNA/RNA Rozita Tebyanian
DNA: is a polymer of two polynucleotide strands wrapped in a right handed
double helix. DNA has a sugar (deoxyribose) phosphate backbone, and
has the bases paired via hydrogen bonding (A-T and G-C). DNA carries the
genetic information (genes) of an organism (sum=genome).
RNA: is a polymer of polynucleotide strands. It has a sugar (ribose)
phosphate backbone, and has the bases A, U, G, C. It consists of three
types: messenger RNA, transfer RNA, and ribosomal RNA.
mRNA: is an RNA species produces by transcription that specifies the
amino acid sequence of the polypeptide.
rRNA: The RNA present in ribosomes. Ribosomes contain several types of
single-stranded ribosomal RNA that contribute to ribosome structures and
are also directly involved in protein synthesis.
tRNA: A small RNA molecule, that binds to an amino acid and delivers it to
the ribosome for incorporation into a polypeptide chain during translation.
320 Molecular Biology: Transcription/Translation Habeeb Balogun
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Transcription: is the mechanism by which a template strand of DNA is utilized by
specific RNA polymerases to generate one of the three different classifications of RNA.
These 3 RNA classes are:
1. Messenger RNAs (mRNAs): This class of RNAs are the genetic coding templates
used by the translational machinery to determine the order of amino acids incorporated
into an elongating polypeptide in the process of translation.
2. Transfer RNAs (tRNAs): This class of small RNAs form covalent attachments to
individual amino acids and recognize the encoded sequences of the mRNAs to allow
correct insertion of amino acids into the elongating polypeptide chain.
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3. Ribosomal RNAs (rRNAs): This class of RNAs are assembled, together with
numerous ribosomal proteins, to form the ribosomes. Ribosomes engage the mRNAs
and form a catalytic domain into which the tRNAs enter with their attached amino acids.
The proteins of the ribosomes catalyze all of the functions of polypeptide synthesis.
All RNA polymerases are dependent upon a DNA template in order to synthesize RNA.
The resultant RNA is, therefore, complimentary to the template strand of the DNA duplex
and identical to the non-template strand. The non-template strand is called the coding
strand because its' sequences are identical to those of the mRNA. However, in RNA, U
is substituted for T.
Translation:
Translation proceeds in an ordered process. First accurate and efficient initiation
occurs, and then chain elongation and finally accurate and efficient termination must
occur. All three of these processes require specific proteins, some of which are ribosome
associated and some of which are separate from the ribosome, but may be temporarily
associated with it.
The ribosome binds to the mRNA at the start codon (AUG) that is recognized only by the
initiator tRNA. The ribosome proceeds to the elongation phase of protein synthesis.
During this stage, complexes, composed of an amino acid linked to tRNA, sequentially
bind to the appropriate codon in mRNA by forming complementary base pairs with the
tRNA anticodon. The ribosome moves from codon to codon along the mRNA. Amino
acids are added one by one, translated into polypeptidic sequences dictated by DNA
and represented by mRNA. At the end, a release factor binds to the stop codon,
terminating translation and releasing the complete polypeptide from the ribosome. One
specific amino acid can correspond to more than one codon. The genetic code is said to
be degenerate.
320 Molecular Biology: Application Molecular/Genomics
Genomics: we use DNA renaturation, by denaturing and renaturing DNA we can manipulate it and put it
back together. Cot curves show highly repetitive, middle repetitive and unique DNA. DNA sequencing
can be done using gel electrophoresis, or through automated DNA sequencing. Restriction enzymes cut
DNA in specific spots which can then be used with Southern blotting methods. Recombinant DNA uses
restriction enzymes to splice in plasmid DNA into the bacterial DNA. Cloning is also useful, and we can
get large genomic DNA libraries. Colony hybridization uses probes to find specific genes. PCR is able to
amplify targeted sequences and replicate them enormously.
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322 Cell Physiology Histology: Cell Physiology Christina Pereira
Cell-definition-structural units of living things that perform the fundamental functions of
life
Basic requirements
o Oxygen, water, constant temperature, moderate pressure, ~ 50 nutrients
3 Major parts
Nucleus- gene containing control center of cell, dictates kinds and amounts of proteins to
be synthesized at a given time (gene expression)
o
Nuclear envelope-double bilayer membrane with pores that regulates the
passage of substances to and from the nucleus
§ Outer membrane is continuous with the rough ER and is studded with
ribosomes
Nucleolus-site of ribosomal RNA transcription and ribosomal subunit
o
assembly
o
Chromatin-genetic material composed of DNA and histones, arranged in
fundamental units called nucleosomes, form condensed chromosomes when the
nucleus starts to divide
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Cytoplasm-region between the nucleus and plasma membrane; site where most
metabolic functions take place
o
sugars,
o
Cytosol-fluid portion comprised of water with dissolved protein, salts,
and other solutes
Inclusions-chemical substances such as glycogen granules, and pigment
granules and lipid droplets
o
Cytoplasmic organelles (cell specializations) – specialized cellular
structures
that perform specific functions (see end of document for
descriptions)
§ Membranous – mitochondria, peroxisomes, lysosomes, ER, Golgi
apparatus
§ Nonmembranous (not surrounded by membrane) – centrioles,
ribosomes,
cytoskeletal elements

Plasma Membrane-outer boundary that separates intracellular fluids and solutes from
extracellular ones, it is comprised of a fluid lipid bilayer and associated proteins; acts as
a semi-permeable barrier
o
Bilayer consists of 3 major classes of lipids:
§ Phospholipids-have a polar (hydrophilic) head group and 2 long chain
fatty acids (hydrophobic) attached to a glycerol backbone
§ Glycolipids-lipids with bound carbohydrate found only in outer lipid
layer of
PM
§ Cholesterol-stabilizes membrane fluidity (~20% of PM lipids), increases
and
decreases fluidity of plasma membrane
o
PM also contains membrane proteins:
§ Integral membrane proteins- partially imbedded/inserted, or of the
transmembrane variety that span the membrane completely
§ Peripheral proteins-not embedded in the bilayer; attached to the
surface of the membrane
§ Functions of membrane proteins: transport, enzymatic activity,
receptors for signal transduction, intercellular joining, cell-cell recognition, and
attachment to cytoskeleton and extracellular matrix
o
Glycocalyx-glycoprotein and glycolipid area surrounding the PM provides
biological markers by which cells recognize one another
o
Microvilli-finger-like extensions of the PM that increase surface area
o
Membrane junctions: specialized protein complexes that help join cells together or
allow them to communicate
§ Tight junctions-impermeable junctions that encircle the cell to keep substances
from passing between cells
§ Desmosomes-anchoring junctions scattered along the sides of cells to hold
cells together
§ Gap junctions-form channels (connexons) between cells that allow small
molecules to pass between cells; cells w/ functional gap junctions are “communicating”
cells that work as a synchronized group
Molecules that pass through gap junctions may be: ions, small signaling
molecules (cAMP, IP3), energy molecules (ATP,GTP) or toxins
Membrane Transport – Passive Transport
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Diffusion: driven by kinetic energy of molecules
Simple diffusion: nonpolar and lipid soluble substances diffuse directly through the lipid
bilayer
Facilitated diffusion: transported substances bind carrier proteins or pass through protein
channels
o Carrier proteins: are transmembrane proteins that show specificity for certain
polar molecules including sugars, AA, ions and facilitate their movement across the
membrane
o
Channels: transmembrane proteins that selectively transport ions or water
through the membrane via a central “pore”
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Osmosis: diffusion of water (solvent) across a semi permeable membrane (simple
diffusion or aquaporin channel mediated)
o
Water always moves from high concentration region to lower concentration region
o
Higher osmolarity (total concentration of solute particles in a 1L solution) solution
has a lower water concentration and a higher osmotic pressure
o
Net osmosis will occur until hydrostatic pressure equals the osmotic pressure

Filtration: passage of water and solutes through a membrane by hydrostatic pressure
o
Pressure gradient pushes solute containing fluid from higher pressure area to a
lower pressure area
Membrane Transport – Active Transport

Uses ATP and carrier proteins to move solutes across membrane
o
o
o
protein
Symport – 2 substances are moved across membrane in same direction
Antiport – 2 substances are moved across membrane in opposite directions
Primary Active Transport – hydrolysis of ATP phosphorylates the transport of
causing conformational change that mediates transport
drive
o
Secondary Active Transport – use of an ATP-requiring exchange pump indirectly to
the transport of other solutes
o
Vesicular Transport – transport of large particles, fluid and macromolecules across
plasma membrane
§ Endocytosis – enables large particles and macromolecules to enter the cell via
protein (usually clathrin) coated pits
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Phagocytosis – pseudopods engulf solids to bring them into the cell; a
phagosome forms inside the cell which fuses w/ lysosome
Pinocytosis – plasma membrane infolds bringing extracellular fluid w/
dissolved molecules into the cell
Receptor Mediated endocytosis – provides the main route for endocytosis
and transcytosis of specific molecules
o
Non-clathrin coated vesicles – caveolae are sites for a variety of
signaling
molecules
§ Exocytosis – moves substance from the cell interior to the extracellular space
(involves SNARE proteins)
Tonicity – how a solution affects cell volume
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Isotonic – solutions w/ same solute concentration as that of cytosol à no change
in cell shape
·
Hypertonic – solutions having greater solute concentration than that of the
cytosol à cells shrinks
·
Hypotonic – solutions having a lesser solute concentration than that of the
cytosol à cell swells
Cytoplasmic organelles (Cell Specializations)
Cytoskeleton
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The skeleton of the cell; provides support and mediates intracellular movements
o
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Dynamic, elaborate series of protein rods running through cyctosol
3 kinds of cytoskeletal elements
o
Microtubules-Long, thin cylindrical structures made of tubulin protein and
associated proteins
§ Function: provide structural support for the cell, function in various
types of
cellular movement, and are components of cilia, flagella, and
centrioles
o
Intermediate Filaments-Protein fibers with high tensile strength and the
most stable cytoskeletal elements, that are composed of varying types of protein
§ Function: support the cell by resisting mechanical forces acting on the
cell
and help control cell shape (Ex. keratin, neurofilaments)
o
Microfilaments-The smallest diameter protein filaments of the cytoskeleton
comprised of actin
§ Function: involved in muscle contraction and other types of
intracellular movements
Cytoplasmic Extensions
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Cilia-short, PM covered cell surface projections that move in unison, creating a
unidirectional current that moves substances across cell surfaces; contains pairs of
bundled microtubules (Ex. respiratory tract, female reproductive tract)
Flagella-Long, PM covered cell surface projections that propel a cell; contain pairs of
bundled microtubules (Ex. sperm)
Organelles
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Mitochondria-Rod-shaped, double membrane structure; folded inner membrane contain
electron transport chain; mitochondria have their own DNA and are self-replicating;
inherited from the mother
o
Function: primary site of ATP production via TCA cycle and oxidative
phosphorylation;
Ca 2+
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Rough ER-Stacked membrane system enclosing a lumen that is continuous with the
nuclear envelope; externally studded with ribosomes
o
Function: Site of attachment of core sugar groups to proteins, site of cholesterol
synthesis, and transport of membrane, secretory, and lysosomal proteins to Golgi
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Smooth ER-Membrane system of sacks without ribosomes
o
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Function: Site of lipid metabolism, steroid synthesis, and drug detox
Golgi apparatus-Membrane system of vesicles and stacked, flattened membrane sacs
o
Function: post translation modifications; segregation and packaging of proteins for
secretion or incorporation into the PM or lysosomes
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Peroxisomes-Contain oxidase enzymes (catalase-breaks down peroxide) that function
to detoxify substances
Lysosomes-Contains acid hydrolases that mediate intracellular digest of molecules
Centrioles-Paired, elongated star-shaped bodies comprised of triplets of microtubules
that are part of the centrosome
o
Function: help organize microtubule network to form spindle during mitosis; form
base structures of cilia and flagella
the
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Ribosomes – particles containing protein and rRNA; site of protein synthesis
322 Cell Physiology Histology: Cell Physiology Christina Pereira
Generation of a Resting Membrane Potential
Membrane potential- a voltage across a membrane
Resting Membrane Potential – voltage across the plasma membrane of a cell at rest (not
stimulated or damaged)
o
Results from Na+ and K+ concentration gradients across the membrane and their
different permeabilities
o
Resting membrane potential is maintained by active transport of ions
o
Ranges from -20 to -200 mV
Purpose of membrane potential: to provide an electrochemical potential for:
o
Changes in membrane potential during excitation of neurons and muscle cells
o
For co-transport of substances into cells
Membrane Receptors – diverse group of integral proteins and glycoproteins that serve as
binding sites for ligands or other cells and function in cell signaling
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Cell Adhesion Molecules (CAMs) – plasma membrane receptors, usually glycoproteins,
that:
o
Anchor cells to the extracellular matrix (ECM) and to each other
§ Are a component of desmosomes
o
Function in mediating migration of cells during development and in binding white
blood cells to concentrate them near injured or infected tissues
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Contact Signaling Receptors – allow cells to recognize each other by direct contact
o
o
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Important in development and immunity
Specific sugar groups on glycoproteins are major means for recognition
Chemical Signaling Receptors:
o
Enzyme Receptors – binding of a receptor induces an enzyme reaction
o
Chemically Gated Channel-linked Receptors – ligand binding to chemically gated
channel-linked receptors cause opening or closing of ion channels in nerve and muscle
tissue
o
G-protein linked Receptors – ligand binding to a receptor activates a heterotrimeric
G protein (GTP-binding pretein)
Operation of a Heterotrimeric G Protein

1) An extracellular ligand (1st messenger) binds to a specific plasma membrane receptor
protein (G-protein-linked receptor or 7-transmembrane protein)
- 1st messengers include: ACh, growth factors, peptide neurotransmitters, some
peptide hormones
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2) The receptor activates a G protein causing GTP to bind and GDP to be released from
the G-protein. The activated G protein then:
3) Relays the message to an effector protein
- effector proteins include: enzymes, ion channels, AC, PLC or K+ channel (or
PDE in photoreceptors)

4) The effector produces a 2nd messenger inside the cell (can be more than 1 second
messenger)
- 2nd messengers include: cAMP, cGMP, IP3, diacylglycerol, Ca2+
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5) The 2nd messenger activates a kinase (cascade) or ion channel
6) The activated kinase or channel can trigger a variety of cellular responses
Cell Life Cycle – the series of changes a cell goes through from the time it is formed until it
reproduces
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Interphase
o
o
o
o
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G1 – vigorous growth
S – growth and DNA synthesis
G2 – more growth and preparation for cell division
G0 – cells that permanently cease dividing; normal metabolic activity
Mitotic Phase (Cell Division)
o
o
Mitosis – nuclear division
Cytokinesis – division of the cytoplasm
Control of Cell Division
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Surface to volume ratio of cells
Chemical signals such as growth factors and hormones
Contact inhibition
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Cyclins and cyclin-dependent kinases (Cdks) complexes
Developmental Aspects of Cells
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All cells of the body contain the same DNA but develop into all the specialized cells of
the body
Cell specialization (also called cell differentiation) is determined by the kind of proteins
that are made in that cell due to different genes being turned off or on.
Cells in various parts of the embryo are exposed to different chemical signals that
channel them into specific differentiation pathways
Cell aging
o
Wear and tear theory attributes aging to chemical insults and formation of free
radicals
that have cumulative effects throughout life
o
Genetic theory attributes aging to cessation of mitosis that is programmed into our
genes
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322 Cell Physiology Histology: Histology Z Liu
1. Histology: The science concerned with the minute structure and organization of cells
and tissues in relation to their function
2. Definition of Tissue-Collection of similar cells that perform a common function and the
surrounding intercellular substances
3. Organ: structure composed of 2 or more tissues that perform specific functions
4. 4 types:
a. 1. Epithelial – covering, lining, and gland forming cells
b. 2. Connective – support and binding
c. 3. Nervous – communication and control
d. 4. Muscle – movement
Epithelial tissue - A sheet of cells that covers a body surface, lines a body cavity, or
forms a gland
. Functions
i.
Protection (skin)
ii.
Absorption (intestine)
iii.
Filtration (capillaries)
iv.
Excretion (kidney tubule cells)
v.
Secretion (stomach)
vi.
Sensory Reception (taste cells)
a. Characteristics - Avascular, regenerative, highly polar
Classfication
. shape
.
Squamous: flattened
i.
Cuboidal: cube like
ii.
Columnar: elongated
a. arrangement
.
Simple: single layer
i.
Stratified: 2 or more layers
Major types of epithelia
7.
Simple Epithelial: single layer
a. Simple Squamous: flattened cells with sparse cytoplasm
i.
Exchange of substances by diffusion or filtration
ii.
Endothelium: lines blood vessels, heart, and lymphatic vessels
iii.
Mesothelium: lines ventral body cavity and organs
b. Simple cuboidal - single layer of cuboidal cells
.
Functions- secretion, absorption
i.
ex. Kidney tubule cells
c. Simple columnar- single layer of tall cells, usu. with oval nuclei
Functions- secretion, absorption
i.
exs. Ciliated – respiratory tract
1. non-ciliated – digestive tract
d. Pseudostratified columnar - similar to simple columnar-not
really stratified
8. Stratified epithelia - 2 or more layers of epithelial cells
. Stratified squamous-usually thick, outer layers flatter
.
protective role - Skin, mouth, esophagus
a. Stratified cuboidal- ducts of glands (sweat, mammary)
.
b. Stratified columnar - ducts of glands, urethra
9. Transitional epithelia-resembles both stratified squamous and stratified cuboidal -
has stretch properties
. ex. Bladder
10. Glandular epithelia – epithelia that form a gland or part of a gland
. Definition of gland- 1 or more cells that make and secrete a cellular
product
.
Exs of secreted products: saliva, hormones, mucin\
i.
Most glands form by invagination of an epithelial sheet
a. Endocrine-- secrete hormones/product → into surrounding extracellular
space → taken up by blood, lymph and travel to target
organs
i.
mostly ductless glands
1. adrenal gland, pituitary gland
a. Exocrine- secrete product → onto epithelial surface or into body cavities
.
mostly epithelia-derived
i.
most have a duct (except unicellular exocrine glands)
more numerous than endocrine glands
may be unicellular or multicellular
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322 Cell Physiology Histology: Histology Z Liu
Connective Tissue
1. 4 subclasses: CT proper, Cartilage, bone, blood
2. Major Functions: support and binding, protection, insulation, transportation of
substances
3. Characteristics of CT
a. All are derived from the mesenchyme (mesochyme): embryonic tissue of the mesoderm
b. Variable vascularity
c. Low cellular content; mostly ECM
Structural Elements (ground substance and fibers = ECM)
d. Ground Substance: amorphous material that fills the space between CT cells;
contains fibers and holds fluid
i.
Composed of interstitial fluid, adhesion proteins, proteoglycans
ii.
Proteoglycan = protein core + polysaccharide
e. Fibers: elongated fibrous protein structures for support (extracellular)
.
Collagen: collagen protein monomers secreted into the ECM; assembled
into fibers
i.
Elastic: made of elastin; coiled structure that stretches and recoils; found
in skin, lungs, blood vessels
ii.
Reticular: fine protein fibers; support soft tissues and small vessels
f. Cells
1. Immature = blast; actively mitotic cells that form the ECM and produce more blast
2. Mature = cyte; maintain health of ECM
3. Bone: osteoblast/osteocyte
4. CT Proper: fibroblast/fibrocyte
5. Cartilage: chondroblast/chondrocyte
6. Blood: hemocytoblast/blood cell, corpuscle, lymphocyte/erythrocyte
4. Types of CT
a. Connective Tissue Proper.
i.
Loose: most widely distributed; absorbs H2O; usually vascular
ii.
Aerolar
1. Gel like matrix with 3 fiber types
2. Found under epithelial tissue and surrounding capillaries (base of
mucous membranes)
iii.
Adipose
1. Stores nutrients, cushions, prevents heat lost
2. Found in hypodermis, abdomen, breasts
iv.
Reticular
1. Network of reticular fibers in ECM
2. Found in lymphatic tissues, bone marrow
v.
Dense: durable; used for structure/binding, found in tendons,
ligaments, dermis, walls of large arteries
b. Cartilage- non-vascular. resilient, flexible CT
.
hyaline cartilage - most abundant cartilage type- “gristle”; provides firm
support
matrix appears amorphous and glassy
ii.
iii.
iv.
1. exs.: nose, trachea, larynx, ends of long bones
elastic cartilage- abundant in elastin fibers-give extra flexibility
exs: ears, epiglottis
fibrous cartilage- absorbs compressive shock well; contains thick
collagen fibers
1. exs: intervertebral disks, knee
b. Bone
ii.
iii.
iv.
Osseous tissue; matrix similar to cartilage except harder due to
collagen and Ca2+
Site of blood cell formation
Vascularized
b. Blood-blood cells surrounded by a fluid matrix; fibers are soluble proteins
(fibrinogen) that aggregate and become visible upon clotting
Covering and Lining Membranes (count as organs)
1. Definition-a continuous multicellular sheet composed of at least 2 primary tissue
types: an epithelium bound to an underlying layer of CT proper
2. 3 major types
a. Cutaneous (skin)- comprised of keratinized stratified squamous
epithelium (epidermis) firmly attached to a thick layer of dense CT
(dermis); dry membrane
b. Mucous (mucosae)-comprised of stratified squamous or simple columnar
epithelium with underlying loose CT called Lamina propria
i.
Has wet membranes bathed by secretions (mucous or urine)
Found in open body cavities- digestive tract, respiratory tract, and
urogenital tract.
ii.
adapted for: absorption and secretion
a. Serous (serosae)- simple squamous epithelium with underlying loose CT;
double-walled “sacs” containing fluid; wet membranes
b. Found in closed body cavities (thorax, abdominal cavities)
.
parietal surface – faces the outside surface of the organs
i.
visceral surface – closest to the visceral organs
ii.
3 types of serous membranes:
i.
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pleura- serosae lining the thoracic wall and covering the
lungs
pericardium-serosa enclosing the heart
peritoneum-serosae of the abdominal cavity and visceral
organs (mesothelium)
Nervous Tissue-makes up the nervous system: brain, spinal chord, nerves and sensory
cells
1. Neurons-highly specialized cells that generate and conduct electrical
signals; usually contain processes (extensions of the cell)
i.
dendrites – carry electrical signals toward the cell body
ii. axons – carry electrical signals away from the cell body
3. Supporting cells (glia)- non-neuronal cells of the nervous system that
insulate, protect, support and enhance the electrical activities of neurons
Muscle Tissue-highly cellular, well-vascularized tissue composed of elongated cells
containing actin and myosin filaments, that is responsible for most body movements
1. Skeletal muscle cells- long cylindrical multi-nucleate cells, striated
Fig. 4.10a (called skeletal muscle fibers) function in voluntary movement
2. Cardiac muscle cells- shorter, uni-or binucleate cells with branching fibers
that join at intercalated discs, contain gap junctions ; found only in the heart
i.
Striated, function in involuntary movement
3. Smooth muscle cells -spindle-shaped, uni-nucleate cells with no striations
1. function in involuntary movement
5.
Terms used to describe altered cells, tissues, and organs
o
Hypertrophy: enlargement due to increase in size of cells
o
Hyperplasia: enlargement due to an increase in cell number
o
Atrophy: decrease due to decrease in size or number of cells
o
Metaplasia: altered differentiation of cells to a type different than in the original
tissue; can lead to cancer
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322 Anatomy & Medical Terminology: Abdominal and thoracic cavities
David Luc
Abdominal and thoracic cavities
What are the three different planes of the body?
Frontal, Median (midsagittal), and Transverse plane
Which cavities are encompassed within the Dorsal body cavity?
Cranial cavity and Vertebral cavity
Which two cavities are encompassed within the Ventral body cavity?
Thoracic and Abdominopelvic cavity
What separates the Thoracic cavity from the Abdominal cavity?
The diaphragm
What are the four quadrant of the abdominal cavity?
Upper right, lower right, upper left, lower left
Which quadrant is the majority of your liver located?
Upper right quadrant
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322 Anatomy Medical Terminology: Muscular and skeletal systems
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Skeletal System:
A. Components:
a. Bones-90% of the mass of the skeletal system
b. Joints-between bones
c. Cartilage-3 types
d. Ligaments-connects bones to bones
B. Functions of the Skeletal System
a. Support of the body-rigidity
b. Aids in movement-attachment site for muscles
c. Protection-visceral organs
d. Blood cell production-hematopoesis
e. Mineral homeostasis-Ca +2 reservoir
C. Joints
a. Fibrous-made of fibrous dense CT tissue; most are unmovable; no joint cavity
b. Cartilaginous-made of cartilage; moveable but no joint cavity
i. Example- ribs and end of long bone
c. Synovial-moveable; have joint cavity with synovial fluid; made of cartilage and
fibrous CT tissue.
d. Bursae-flattened fibrous sacs near synovial joints; contains synovial fluid and
reduces friction.
Bone Classification, Growth and Homeostasis:
Bones are grouped into the axial skeleton and the appendicular skeleton. Fig 6.1
1. Axial skeleton: skull, vertebral column and rib cage
2. Appendicular skeleton: bones of the upper and lower limbs and the girdles
(shoulder bones and hip bones)
3. Classification based on shape: long, short, flat, irregular (Fig 6.2-not req.)
Compact Bone: comprised of pillar-shaped structural units called osteons comprised of
layers (lamellae) of collagen fiber with osteocytes between the layers and blood vessels
and nerves running through the center.
Fig 6.6
Spongy Bones: bone with a honeycomb-like structure found internal to compact bone
that contains red or yellow marrow. Red marrow is the site of hematopoesis.
Hematopoesis-red blood cell formation
Both the internal and external bone surfaces are covered with a double-layered
membranous tissue called the endosteum (internal covering) and
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the periosteum (external covering) containing connective tissue superficial to a layer of
bone-forming and bone-destroying cells:
Osteoblasts-bone forming
Osteoclasts-bone destroying (reabsorption-reabsorbs minerals into the blood)
Osteocytes-helps maintain bone matrix made by osteoblasts
In osteoporosis, bone degradation (reabsorption) outpaces bone deposition.
Bone is degraded and Ca +2 released in response to a need for calcium in the body; this
is controlled by parathyroid hormone (PTH)
Fig 6.12
PTH stimulates osteoclasts
PTH also stimulates kidney to convert Vit D to active form (calcitrol) which increases
Ca+2 absorption from the intestine.
Calcium salt deposit in bone is stimulated by calcitonin-produced in the thyroid when
calcium levels are high
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Muscular System
A. Functions of the Muscular system
a. Movement
b. Heat generation
c. Maintenance of posture
d. Stabilization of joints
B. Muscle Tissue/Muscles
a. Common properties of the 3 different muscle types:
i. Comprised of cells called ‘muscle fibers’
ii. Contain myofilaments (thick, thin, elastic)
iii. Function in movement
C. Skeletal Muscles:
Fig 9.2
a. Voluntary muscle, striated, made of muscle cells, CT wrapping, blood vessels, and
nerves.
a. Muscles are wrapped in a CT covering called the epimysim.
b. Bundles of skeletal muscle cells (called fasicles ) are wrapped in a CT covering
called the perimysium.
a. Individual skeletal muscle cells (muscle fibers) are wrapped in the CT covering
called the endomysium (surrounds plasma membrane of the cell).
Microscopic anatomy of skeletal muscle Fig 9.3, 9.5
1. Skeletal muscle cells (muscle fibers)-long cylindrical cells with multiple nuclei formed
by fusion of embryonic cells; contain myofibrils.
2. Sarcolemma-specialized plasma membrane of skeletal muscle cells; invaginates
into t-tubules at the A-band I-band junction
3. Sarcoplasm-cytosol of a muscle cell.
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4. myofibrils- (an organelle) rod-like structures comprised of proteins (actin, myosin,
nebulin, titin, tropomysin, troponin) contained within skeletal muscles cells that re
the contractile elements.
Composed of myofilaments (3 types)
a. Thick filament-comprised of myosin, with ‘head’ and ‘tail’ regions.
b. Thin filament-comprised of mostly actin; also contains the regulatory
proteins tropomysoin and troponin
c. Elastic filaments- comprised of titin
Banding pattern on the myofibrils responsible for striations.
a. A band- darker region containing thick filaments (myosin filaments)
b. I band- lighter region lacking thick filaments
c. Z disc- center region of I band containing the protein nebulin that anchors the thin
filament (actin filament).
d. H zone- lighter region in the center of each A band lacking thin filaments when the
muscle fiber is relaxed muscle.
5. sarcoplasmic reticulum- high specialized smooth endoplasmic reticulum of muscle
cells that forms a network of tubules around each myofibril within the muscle cell;
regulates the intracellular levels of Ca +2 by storing Ca+2 and releasing it when needed
for muscle contraction.
6. sacromere- a muscle fiber segment from Z disc to Z disc; ‘contractile units’
Skeletal Muscle Contraction
Fig 9.6
sliding filament theory- proposed mechanism of contraction that state that during
contraction, the thin filaments (actin) slides past the thick filament (myosin) so that they
come closer together and then overlap; the thick filament remains essentially in the same
position.
a. Slides past and Z disc pull together, filament stays about the same size (doesn’t
contract).
I bands shorten and the H zones disappear during contraction due to the sliding
movement of the thin filaments.
Thin filaments sliding is medicated by ‘cross bridges’ (myosin heads, see table 9.1)
attaching ratcheting, and detaching from actin filaments.
Fig 9.11
ATP is required for cross bridges attachment and detachment
Ca +2 is also required
A. Cardiac Muscle Contraction:
a. Mechanism similar to skeletal muscle contraction (SR Ca+2 release, sliding filament
mechanism, troponinC regulation, etc…)
b. Nervous system input signal may cause excitation or inhibition, ANS (autonomic
nervous system); (skeletal muscle always excitation)
c. Speed of contraction is slower than skeletal muscle
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d. Cardiomyocytes display “autorhymicity”
i. Autorhymicity-tend to naturally beat, spontaneously rhythmically firing of some
cells
B. Smooth Muscle Contraction:
read pp 311-312
i. Myofilaments pull together during contraction in a sliding filament mechanism Ca
+2 regulates contraction through binding to calmodulin, rather than troponinC.
ii. Pacemaker cells present that can regulate contraction; cells which have
autorhythmicity.
iii. Smooth muscles cells have gap junctions to coordinate contraction.
322 Anatomy Medical Terminology: Medical Terminology
Anatomical positionFigure 1.7
human body erect, arms at sides, palms forward, feet together.
Regional Terms2. Directional termsTable 1.1
a. Superior-towards the head end or upper end of a structure of the body; above.
b. Inferior- away from the head end or toward the lower part of a structure or the
body; below.
c. Anterior (ventral)- toward or at the front of the body; in front of
d. Posterior (dorsal)-toward or at the back of the body; behind
e. Medial-toward or at the midline of the body; on the inner side of
f. Lateral-away from the midline of the body; on the outer side of
g. Intermediate-Between a more medial and more lateral structure
h. Proximal-Closer to the origin of the body part or the point of attachment of a limb
to the body trunk.
i. Distal-Farther from the origin of a body part or the point of attachment of a limb to
the body trunk.
j. Superficial (external)-toward or at the body surface
k. Deep (internal)-away from the body surface; more internal
3. Body Planes
Figure 1.8
a. Sagittal/midsagittal/parasagittal (median)- cut down middle into right and left
parts, if cut exactly in half then the midsagittal line.
b. Frontal (Coronal)- divides body into anterior and posterior section or ventral and
dorsal section.
c. Transverse (Horizontal)- divides the body into superior and inferior sections.
i. Oblique-transverse but at a slight angle.
 Planes are also used for referring to sections of organs
4. Body Cavities
Figure 1.9, 1.10
a. Dorsal Body Cavity- comprised of:
i. Cranial cavity-brain
ii. Vertebral-spinal chord
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c.
d.
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b.
c.
d.
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b.
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d.
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b.
c.
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b. Ventral Body Cavity- contains the visceral organs (soft body) walls and surfaces
of organs lined with serous membranes (see below) comprised of:
1. Serous Membrane- are fluid filled sac, thin membrane surrounds organ and fluid
filled, double layer membrane.
ii. Thoracic cavity:
1. Mediastinus-central portion; contains heart, esophagus, trachea.
2. Pleural- contains lungs
a. Pleural cavity lateral to the mediastinus cavity
iii. Abdominopelvic cavity:
1. abdominal cavity-contains stomach, spleen, liver, intestines, gallbladder, and
pancreas.
2. pelvic cavity-contains bladder, reproductive organs and rectum.
a. The thoracic and abdominopelvic cavities are separated by the diaphragm.
3. abdominopelvic quadrants- Figure 1.12
a. four quadrants-upper/lower right and upper/lower left
iv. Other Cavities: (know locations)
1. oral
2. nasal
3. orbital-eyes
4. middle ear
5. synovial-movable joint cavities
Joe Walker Practice Quiz Medical Terminology:
The cervical region is ________ to the thoracic region.
Inferior
Superior
Medial
Distal
Your nipple is _______ to your spine.
Anterior
Lateral
Ventral
All of the above
The rib cage is _______ to the lungs.
Deep
Posterior
Superficial
Ventral
The ______ is deep to the ______
Skin / muscle
Muscle / skin
Spine / esophagus
Popliteal / patellar
5.
Which region would not be considered ventral?
a.
Vertebral
b.
Sternal
c.
Umbilical
d.
Thoracic
6.
Which body plane separates the body into ventral and dorsal sections?
a.
Transverse
b.
Coronal
c.
Sagittal
d.
Horizontal
7.
What is a fingertip proximal to?
a.
Wrist
b.
Knuckle
c.
Elbow
d.
All of the above
e.
None of the above
8.
What separates the thoracic and abdominopelvic cavities?
a.
Peritoneum
b.
Visceral pericardium
c.
Diaphragm
d.
Parietal serosa
9.
Where do all of your visceral organs hang out?
a.
Cranial Cavity
b.
Abdominopelvic cavity
c.
Ventral cavity
d.
Vertebral cavity
10. In which quadrant of the abdomen is most of the liver located in?
a.
Right Upper
b.
Right Lower
c.
Left Upper
d.
Right Lower
1
2
3
4
5
6
7
8
9
10
B
D
C
B
A
B
E
C
C
A
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322 Physiology: Cardiac Physiology Amie Darke
Cardiovascular system:
Comprised of : heart & coverings, blood vessels & blood and innervations
Major Components:
Plasma: 55%
Leukocytes & Platelets : 1% combined
Erythrocytes: 45%
Normal blood pH: 7.35-7.45
Hematocrit: Proportion of blood volume occupied by RBC’s
Functions of Blood:
1. Distribution: deliver O2 & other nutrients
2. Regulation: maintain body temp, pH, proper fluid volume
3. Protection:preventing blood loss through *hemostasis: preventing infection through antibodies
**Plasma is 90% water 10% solutes**
Erythropoiesis: genesis of RBC’s
Heart: function is to transport blood throughout the body for nutrient/waste exchange
Blood enters through the Atria
Blood leaves through ventricles
Pathway
FLOW:
Rt atrium→Rt ventricle→pulmonary trunk→pulmonary arteries→Capillary beds of lungs→pulmonary
veins→left atrium→left ventricle→aortic arch→aorta→arteries→tissue of capillary beds→veins→vena
cava→rt atrium
Systemic Circuit: general circulation
arteries→oxygenated blood
veins→UNoxyenated blood
Pulmonary Circuit:
Pulmunary arteries→UNoxygenated blood
Pulmonary veins →oxygenated blood
*Hemostasis: COMPLEX series of reactions that stop bleeding after blood vessel is injured: involves
numerous clotting factors
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322 Physiology: Renal Physiology Amie Darke
RENAL SYSTEM
Components:
Kidneys
Urinary bladder
Ureter
Urethra
Renal artery
Renal vein
Functions:
Excretion
Regulation of blood & volume
Production of erthropoetin
Metabolism of vitamin D
Production of rennin (BP regulation)
Kidney structure:
Cortex: “outer layer” contains bulk of nephrons-giving it granular appearance
Medulla: layer deep to the cortex-contains collecting ducts
Renal pelvis: collects urine drains to ureters
Kidney lobes: 8 per kidney: includes section of cortex and medulla & associated blood vessels
Fibrous capsule: outer protective covering of kidney-prevents infection from other organs
Microscopic structure of kidneys: several but most important is→
Loop of henle-Important site of Na+ and K+ transport into and out of tubule
FLOW:
Enters into collecting ducts→renal pelvis→ureters→bladder (storage) →urethra→excreted
Remember:
If a drug has a high renal clearance it is eliminated form the body rapidly (reabsorbed poorly)
If drug has a low renal clearance it is eliminated from body slowly(reabsorbed extensively)
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322 Physiology: Nervous System Physiology
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Nervous System Physiology
Nervous System
 General Functions
o Master controlling/communicating system of the body-responsible for all behaviors
o Works with the endocrine system to coordinate the organ systems of the body to
maintain homeostasis
 4 Modes of Function
o Receiving sensory information
o Processing and interpreting sensory input (interpretation)
o Causing a response through motor output to effectors organs
o Storing information (memory)
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Organization of the Nervous System
 CNS
o Brain
o Spinal cord
 PNS
o Nerves, ganglia, and sensory receptors
o Sensory Division-afferent
 Somatic-sensory info from skin and skeletal muscles
 Visceral-sensory info from organs
o Motor Division-efferent
 Somatic-aka Voluntary Nervous System-motor neuron impulses from CNS to
skeletal muscle
 Visceral-aka Autonomic Nervous System (ANS)-visceral motor neuron impulses that
regulate smooth, cardiac muscle, and glandular tissue
 Sympathetic-Fight or flight
 Parasympathetic-Rest and digest
Cellular Components
 Neuroglia-Non-neural cells of the CNS and PNS that control the chemical
environment of the CNS and PNS and insulate, protect, and promote the growth of
neurons
o CNS cells
 Astrocytes- starshaped; most abundant cell type in the CNS; function to control
chemical environment ; part of the blood-brain barrier (BBB)
 Ependymal-line central cavities of the brain and spinal cord-epithelial cells
 Oligodendrocytes-myelinate long axons
 Microglia-protective role-macrophages of the NS
o PNS cells
 Schwann cells-myelinate axons-also function in peripheral nerve regeneration
 Satellite cells-surround neuron cell bodies in ganglia-control chemical environment
 Neurons-highly specialized cells of the PNS and CNS that conduct info in the form
of electrical impulses (depolarization of the PM)
o Types
 Function
 Sensory-conducts impulses from receptors in peripheral body parts into the brain or
spinal cord
 Interneuron-transmits impulses between neurons within the brain and spinal cord
 Motor-conducts nerve impulses from the brain or spinal cord out to effectors
 Structure-multipolar, bipolar, unipolar
o Characteristics
 Long-lived; amitotic (non-dividing), highly differentiated; high metabolic raterequires continuous and abundant supply of glucose
o Structure
 Cell body (soma) and plasma membrane
 Neuronal processes-cytoplasmic extensions of neurons (covered by PM)
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 Dendrites-Afferent-tapered, branching processes that serve as the main receptive, or
input regions of a neuron; transmit signals toward the cell body; usually many per
neuron
 Axon-Efferent-output process of a neuron; carries signals away from the cell
body; usually 1 per neuron; aka “nerve fiber”
o Axon hillock-transition region
o Axon collaterals-branches along the axon
o Terminal branches-branches at the end of the axon
o Boutons-axon terminals-make synapses
o Myelin sheath-proteolipid covering of an axon-insulates fiber-important in
conducting electrical signal
 Bundled Axons
o Tracts in the CNS
o Nerves in the PNS
 Gray Matter-Comprised of neuronal cell bodies and unmyelinated axons
 White Matter-comprised of myelinated axons
The Central Nervous System
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4 MAJOR REGIONS
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o
Cerebral hemispheres-most superior part of the brain; comprised of
cerebral cortex, white matter, and basal nuclei; contains 4 lobes
 Cerebral cortex-outer gray matter region of the cerebral hemispheres; responsible for
higher order thinking, consciousness
 Cerebral white matter-myelinated fiber tracts; mediate communication between
cerebral hemispheres and between cerebral hemispheres and lower brain centers
 Basal nuclei (ganglia)-gray matter areas located deep within the cerebral hemispheres
that function in motor control, cognition, memory; 3 primary structures
 Caudate nucleus
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Putamen
Globus pallidus
Major lobes, Frontal, Parietal, Temporal, Occipital
Ridges called gyri
Major fissures
Longitudinal-lengthwise down the center
Transverse-divides the cerebellum from the cerebral hemispheres
Minor fissures called sulci
o Diencephalon-central core of the brain
 Thalamus-comprised of many nuclei that sort and edit afferent information coming
from motor and sensory areas-relay center
 Hypothalamus-main visceral control center; important for body homeostasis (temp.
control, feeding), reproduction (LHRH), emotions
 Epithalamus-contains pineal gland-releases melatonin-important in sleep/wake
cycle
o Brainstem-portion of the brain connected to the spinal cord that contains nuclei for
autonomic functions and connecting tracts
 Midbrain
 Pons
 Medulla oblongata
o Cerebellum-brain region located dorsal to the brainstem that is involved in
producing smooth, coordinated skeletal muscle activity; processes inputs received from
the motor cortex, brainstem, and sensory receptors to coordinate movement
Other structures of the CNS
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 Function Brain regions-contain structures from more than one brain region that
work together to perform related functions
o Ex. Limbic system-“emotional system” of the brain
 Contains structures from the cerebral hemispheres and diencephalons, specifically
the hypothalamus
 Very complex structurally and functionally
 Contains hippocampus-involved in converting new information into long term
memories
 Brain ventricles-cavities of the brain containing cerebrospinal fluid; 4 of them
o Continuous with each other and the central canal of the spinal cord
o Lined with ependymal cells
o Function: protection-liquid cushion; nourishment-Vit C, Mg 2+, Na+
 Blood Brain Barrier-selective barrier that helps maintain a stable environment for
the brain
o Hydrophobic substances cross more easily
o Important for drug uptake into CNS
o Comprised of brain capillaries, tight junctions, thick basal lamina, and surrounding
astrocytes
 Meninges-3 connective tissue layers that lie external to CNS organs
o Protection
o Contain CSF
o 3 regions
 Dura mater
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 Arachnoid
 Pia mater
 Spinal Cord-bundle of nervous tissue that runs from the based of the skull connected
to the brain stem to the 1st – 3rd lumbar vertebrae
o Function: provides a 2-way conduction system to and from the brain to the PNS
o Major reflex system
o Groups afferent neuron axons enter of the dorsal side-dorsal tracts
o Axon fibers of efferent neurons exit at
o White matter-ascending and descending nerve tracts
o Gray matter-surrounds central cavity containing CSF; divided into sensory
(dorsal/afferent) segments and motor (ventral/efferent) segments
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322 Physiology: Reproductive System Development
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Definition-the study of the life cycle of an organism usually up to adolescence, but
everyone continues to develop until death.
Stages:
a. Pre-embryonic period-all events that occur prior to the fertilization of the ovum
(egg) by the sperm to produce the fertilized egg (zygote).
b. Embryonic period-all events from conceptions (fertilized egg) up to and including
8 weeks of gestation.
c. Fetal period-beginning the 9th week until birth of the neo-nate.
i. The most critical period because undergoes organogenesis-the development of organ
systems and morphogenesis-physically forming.
ii. The greatest chance for malformation during this time frame.
d. Neo-Natal period-infancy to the first year after birth.
e. Childhood- from the end of the first year (infancy) up until puberty (sexual
development)
f. Adolescence- the period from puberty up until totally physical maturation (ending
period varies).
i. Not completely developed until through all these stages.
2. Gametes: Special Characteristics vs Somatic
a. Gametes are haploid.
i. They possess only one set of chromosomes, those that have two diploid.
b. Genome possessed by any gamete is unique to that gamete.
i. All somatic cells have same genome but expressed differently based on the role.
3. Gametogensis-maturation of gametes
a. Overall Process:
i. Origin of the germ cells
ii. Mitotic division to increase the number of germ cells
iii. Production of haploid cells by meiosis
iv. Maturation of Gametes-leads to fertilization.
b. Stage 1-Primordial Germ Cells.
i. Originate outside of the embryonic body.
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Developmental Biology~
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ii. The earliest recognizable precursors of gametes (primordial germ cells).
c. Stage 2-Mitotic Division in Oogonia.
i. Mitotically active germ cells in the female.
ii. Go through a period of intense mitotic activity in the embryo-from second through
fifth month of development, maximum number of germ cells ever found in ovaries.
1. by birth 70% of max germ cells have been lost and then continue to decrease until
menopause.
iii. Then begin a natural degeneration-Atreasia, end a menopause
d. Stage 2-Mitotic Division in Spermatogonia.
i. Mitotically active germ cells in the male.
ii. Mitosis also begins in early embryonic gonads, male germ cells maintain ability to
divide throughout life.
iii. Beginning at puberty, subpopulations of spermatogonia undergoes periodic waves
of mitosis.
e.
Stage 3-Gametogensis-Production of Haploid Cells by Meiosis.
i. Objective of Meiosis: To put just one copy of each of the 23 chromosomes in each
gamete.
ii. Meiosis does this by:
1. Single cycle of DNA duplication followed by
2. Two cycles of nuclear and cell division.
iii. Stage 1-Duplication of DNA
iv. Stage 2-Chromosome Division
1. One major difference:
a. Mitosis passes through cycle once
b. Meiosis passes through cycle twice, leading to a haploid cell.
f. Meiosis and Genetic Variability:
i. Crossing Over-exchange of terminal portions of chromatid arms between
homologous chromosomes
ii. Independent Assortment-chromatids of each homologous pair of chromosomes are
assorted randomly to the daughter cells or gametes.
g. Stage 4: Maturation of gametes-2 processed spermatogenesis and oogenesis.
i. Spermatogenesis: Begins at puberty.
ii. Spermatogonia has two pathways:
1. Replenish germ cells population in gametes
2. Enter mitotic process to give spermatid.
Extra organelles and cytoplasm are removed.
Specialized structures are formed:
1. Head-compact acrosomal vesicle, a giant lysosome with digestive enzymes that are
released with contact of egg.
2. Mid-piece-large concentration of mitochondria and glycogen for energy source.
3.
tail of sperm for propulsion
iii. Oogenesis-egg development:
1. Cycle is not considered complete until gets fertilized.
2. Discontinuous process that begins in fetal life and not complete until egg actually
fertilized.
3. 2 phases:
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a. Fetal development oogonia begins with meiosis.
b. Being again at puberty.
i. Each month after puberty several primary oocytes being development due to
hormones: estrogen, progestin, leutinizing hormone
4. Follicular formation- Soon after meiosis begins of oocyte surrounded by a layer of
cells, the whole group of cells and oocyte is primary follicular.
5. Zonapellucida-non-cellular material (CT like) “membrane’ surrounds part of
follicle that holds those follicular cells in place.
6. FSH-(follicle stimulating hormone) helps un-arrest the primary follicle to give
a secondary follicle stimulated by FSH.
1. Fertilization Process:
a. Stage 1 and 2-Gamete Contact and Fusion
i. Gamete Contact
1. For sperm to come into contact with zonaplacudia must physically break through
follicular cells. Contact with zonaplacudia this triggers released of acrazomal vesicle
ii. Fusion of sperm/egg membrane
1. Triggers extra cellular release of chortical vessels-stimulates reaction, zona
reaction or ‘chortical’ reaction.
a. Biochemical effect-changes character degrades sperm receptors, of zonaplacidua and
some oocytes membranes.
b. Electrical changes of oocyte-depolarization of membrane and prevents additional
sperm from entering.
b. Stages 3 and 4-Late Fertilization
i. Completion of 2nd meiotic division
1. Can’t finish until fertilized
2. Produces a haploid female nucleus.
3. Excess structures degraded as polar bodies.
ii. Formation of zygote
1. Cells have two pro-nuclei (both are haploid). These two pro-nuclei fuse to form
haploid nucleus. About 12 hours after fertilization.
2. Zygote has a diploid nucleus
a. Zygote ends the pre-embryonic period and beings embryonic period.
b. Conceptus-terms used to refer to zygote from point of fertilization until
implantation.
2. Embryonic Period-from zygote to end of 8th week after fertilization.
a. Week 1:
i. About 30 hours after conception begins mitotic division to increase the number of
cells. Begins divisions in uterine tube before implantation.
ii. Cell Divisions: first few divisions are cleavage divisions.
1. Blastomeres-daughter cells of division.
2. Blastomeres (greater than 12) clump together to form morela.
iii. Blastocyst: after enter uterine cavity start forming ball with cells internallyblastocyte.
1. Developed into 2 identifiable structure;
a. Outer layer-similar to the skin of a thin ball-trophoblast.
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i. Ultimately gives rise to extra embryonic tissue that supports development of embryoplacenta.
b. Inner cell mass-central ball of cells-embryoblast.
i. Leads to form embryo itself.
iv. Superficial Implantation
1. About 6 days after conception, trophoblast attaches to uterus= embryo.
2. Embryo implantation begins superficially. Ends Week 1.
b. Week 2:
i. Formation of bilaminar embryonic disc.
1. Separation of cells leads to bilaminar disc/plate of cells called the bilaminar germ
layer.
2. Two cavities:
a. Ambynotic cavity-encircles embryo and serves as a protective cavity.
b. Yoke sac-layer cells adjacent is the hypoblast, the other layer epiblast.
ii. Ambynotic cavity formation.
iii. Completion of Implantation.
c. Week 3
i. Most critical week lie down bases for all tissues in the body.
1. Organogenesis-development of organs.
2. Morphogenesis-development of structure.
ii. Developing human most susceptible to congenital abnormality-structural birth
defect.
1. 1st 2 weeks-die/abort, 3-8 weeks structural abnormalities and > 8 weeks (fetal
period) can have malformations-usually functional though-i.e. mental retardation.
iii. Gastrulation
a. As it precedes the bilaminar disc is converted into trilaminar disc.
i. Establishes the 3 germ layers of the embryo,
1. ectoderm
2. mesoderm
3. endoderm
ii. First sign is the formation of epiblast thickening and produces primitive streak.
2. Onset of morphogenesis- development of body form.
a. 2 major events that occur about end the 3rd week.
i. Establishment of body axis.
1. cranial-caudal axis
2. dorsal-ventral axis
ii. Body shape begins to take form by a series of fold in discs.
3. Onset of Organogenesisa. Happens about end of 3rd week.
b. Signifies development of tissue and organs.
c. End of 3rd week see development of CNS.
i. Blood vessels and heart-angiogenesis, and blood cells and plasma.
d. Fate of germ layers-each gives rise to different types of tissue.
i. Nerve-all nerves tissue of the body is derived from the ectodermal layer
ii. Muscle-all muscle tissue of the body is derived from the mesodermal layer.
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iii. Connective-All connective tissue of the body is derived from the mesodermal
layer, with one exception.
iv. Epithelial- Each of the 3 germ layers give rise to specific types of epithelial tissue.
d. 4th Week:
Mandible, Maxialla, Heart, Forebrain, Upper and lower limb buds, Lens of the eyes.
e. 5th Week:
1. Continued development of head and brain-continues through fetal period.
2. Appearance of elbows, hands, and digits.
3. spontaneous movements such as twitching of trunk and limbs.
f. 6th Week:
i. Eyes become obvious and has pigmentation and reflex response to touch.
g. 7th Week:
i. Maturation of intestines and arms.
h. 8th Week:
i. This week ends the embryonic period.
ii. By the end of the 8th week the human embryo has distinct human characteristics.
3. Fetal Period-from 9th week to until birth.
a. Dominate growth feature is the accelerated growth of the body compared to the
head.
b. If exposed to a tetrategen mostly functional defects.
c. Weeks 9-12 (3 months from fertilization)
i. The head comprised nearly one-half of the fetus size.
ii. Kidney and digestive tract show activity.
iii. The fetus can make a fist with its fingers and movement of digits.
d. Weeks 13-16 (4th month):
i. Lower parts of the body shows accelerated rate of growth-head becomes one-fourth
of fetus size.
ii. Skin appears dark red from circulation of red cells-thin integument.
1. Circulatory system forms.
iii. Fetus begins to stir-arm and leg thrusts readily perceived by mother.
e. Weeks 17-20
i. Fetal heartbeat can be heard.
ii. Integumentary system begins to take final form, including appearance of hair and
nails.
f. Weeks 21-24:
i. Eyelids open and close.
ii. Fingerprints and footprints begin to form.
g. Week 25-28:
i. Fetus is capable of independent life from this time one.
h. Week 29-38:
i. Fat development rapidly over the entire body, smoothing skin and reducing red color
of the skin.
ii. Kidney and digestive tract continue to produce and expel waste products.
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323 Microbiology: Microbial Cell Structure and Function Tejal Bhikha
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Structures Common to ALL bacterial cells: cell membrane, cytoplasm, ribosomes,
one (or a few) chromosomes
Structures Common to MOST bacterial cells: cell wall and surface coating or
glycolayx
Structures found in some bacterial cells: Flagella, Pili, Fimbriae, Capsules, Slime
Layer, Inclusion, Actin Cytoskeleton, Endospores
Glycocalyx: a coating of repeating polysaccharide units, protein, or both
Protects bacteria against phagocytes
Sometimes helps the cell adhere to the environment
Importanta in formation of biofilms
External Structure: Appendages (cell extensions)
Common but not present on all species
Can provide motility –flagella and axial filaments
Can be used for attachment and mating—pilli and fimbriae
Flagella: 3 Parts [Filament, hook, and basal body]
Monotrichous-Single Flagellum
Lophotrichous-small bunches or tufts of flagella emergin from the same site
Peritrichous—dispersed randomly over the structure of the cell
Flagellar Function—Chemotaxis and Photoaxis
Axial Filaments: aka Periplasmic Flagella
In Spirochetes
A type of internal flagellum that is enclosed in the space between the cell wall and the
cell membrane
Pili: made of protein pilin
Found on gram-negative bacteria
Used in conjugation
Fimbriae: Small, bristle-like fibers, most contain protein, tend to stick to each other and
to surfaces
Cell Envelope: Cell wall, cell membrane, and in some, outer membrane
Cell Membrane: also known as cytoplasmic membrane
Site for energy reactions, nutrient processing, and synthesis
Regulates transport
Secretion
Cell Cytoplasm:
Site for many biochemical and synthetic activities
70-80% water
also contains larger, discrete cell masses (chromatin body, ribosome, granules, and
actin strands)
Nucleoid—holds single circular strand of DNA
Plasmids: nonessential pieces of DNA; double stranded circles of DNA
Has protective traits such as drug resistance or the production of toxins and enzymes
Riobosomes:
RNA and proteins
Prokaryotic Ribosome: 70S
Inclusions:
Storehouse for nutrients and some include gas vesicles for buoyancy and flotation
Granules: type of inclusion body
Contains crystals of inorganic compounds
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323 Microbial Cell Structure and function: Disease Causing
Microorganisms Tejal Bhikha
Endospore: 2 phase life-cycle
Phase 1: Vegetative Cell; metabolically active and growing; can be induced by the
environment to undergo spore formation (sporulation)
Phase 2:Vegatative CellàSporangiumàendospore; depletion of nutrients (sporulation)
Heat resistance—high content of calcium and dipicolinic acid
Rickettsias: gram-negative; can’t survive or multiply outside of host cell
Chlyamydias: requires host cell for growth and metabolism
Photosynthetic bacteria: produces oxygen during photosynthesis; some make sulfur
granules or sulfates
Cyanobacteria: Blue-Green Bacteria; used to be called Blue-Green Algae
Gram-negative cell wall
Specialized adaption: thylakoids, cholorphyll a
Gas inclusion
Green and Purple Sulfur Bacteria: photosynthetic
Doesn’t give off oxygen
Live in areas deep enough for anaerobic conditions (sulfur springs, freshwater lakes,
swamps)
Gymnodinium—Toxic algae
G. breve—kills fish, causes minor symptoms in human
Gonyaulax—produces neurotoxins; toxins accumulate in shellfish feeding on
dinoflagellates = paralytic shellfish poisoning
Malaria—Plasmodium species (infective sporozoites)
Sprorozoites travel to liver, divided to make merozoites
Merozoites—enter blood, infect red blood cells, grow, divide, and rupture RBC’s infecting
other RBCs
Symptoms include: anemia, spleenic rupture, hyper immune responses
African Sleeping Sickness--Trypanosoma species, tsetse fly is carrier.
T. brucei, a flagellated protozoan, multiplies in skin, enters blood and lymph.
Patient immune response causes fever, IgM production
Heart and brain involved—6 weeks
Heart failure—6 months
Chargas Disease—Kissing Bug Carrier
Toxoplasmosis—Toxoplasma gondii, cats are primary host, humans are secondary,
can threathen health of the fetus during a primary infection
Vaginitis—Trichomonas vaginalis
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323 Microbial cell structure and function: Microbial metabolism Shivani
Patel
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Microbial Metabolism:
•Metabolism: All chemical reactions and physical workings of the cell; anabolism
and catabolism
-•Functions of metabolism
–Assembles smaller molecules into larger macromolecules needed for the cell
–Degrades macromolecules into smaller molecules and yields energy
-Energy is conserved in the form of ATP or heat
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Metabolism is made possible by organic catalyst or enzymes, that speed up
reactions by lowering the energy of activation. Enzymes are NOT consumed and
an be reused (recycled). They are also able to work at low concentrations.
Catabolism
•Frequently the nutrient needed is glucose
•Most common pathway to break down glucose is glycolysis
•Three major pathways
–Aerobic respiration: Series of reactions that convert glucose to CO2 and
allows the cell to recover significant amounts of energy; O2 is final Electron
acceptor. (38 ATP Produced)
•Oxygen accepts the electrons
•Catalyzed by cytochrome aa3 (cytochrome oxidase)
–Fermentation: When facultative and aerotolerant
anaerobes use only
the glycolysis scheme to ncompletely oxidize glucose; organic molecule is the
final electron acceptor such as; pyrvate, acetaldehyde (2 ATP produced)
–Anaerobic respiration: Does not use molecular oxygen
as the final
electron acceptor; non-oxygen electron acceptors such as So42- NO3- CO3 2- (
2-36 ATP produced)
Biosynthesis and the Crossing Pathways of Metabolism
•The Frugality of the Cell - Waste Not, Want Not
–Most catabolic pathways contain strategic molecular intermediates (metabolites)
that can be diverted into
anabolic pathways
–Amphibolism: The property of a system to integrate catabolic and anabolic
pathways to improve cell
efficiency
–Principal sites of amphibolic interaction occur during glycolysis and the Krebs
cycle
323 Microbial cell structure and function: Host-microbe interactions
Shivani Patel
Host Microbe Interactions
--If normal flora are killed or growth is suppressed, pathogens
may colonize and cause disease
--Infection does not always lead to noticeable adverse effects: Subclinical; unapparent
--Infection that ;results in disease is termed infectious disease
--Infectious disease: The ease of spread of a disease is partly determined by the
infectious dose: The number of organisms required to establish an infection. Diseases
with a small infectious dose spread more easily than those requiring large numbers of
microbes
Avoiding Host Defenses:
1. avoiding phagocytosis: Some pathogens destroy complement components that attract
phagocytes, eg C5a peptidase destroys chemoattractant C5a
Some pathogens produce membrane-damaging toxins that kill phagocytes by forming
pores in the cell membrane; (S. pyogenes makes streptolysin); ctyotoxins
2. Avoid recognition and attachment: Capsules, M protein, FC receptors. Streptococcus
pyogenes have cell walls containing M protein that binds complement regulatory protein
3. Survive within in the phagocyte: escape from phagosome, prevent phagosomelysosome fusion, survive within the phagosome.
--Damage to the host: Many pathogens produce exotoxins that have very specific
damaging effects
--A-B toxins consist of two subunits:
A subunit (active) – the toxic or active subunit
B subunit (binding) – responsible for target cell binding to specific cell receptors
--Phospholipases are group of potent membrane-damaging toxins that remove polar
heads of phospholipids and destabilize the cell membrane
--Endotoxins are LPS from gram negative cell walls and therefore are a fundamental
part of the gram negative organism; Endotoxins are heat stable and therefore not
suitable for use as toxoids; Lipid A is an example!
--Viral pathogenesis: Once attached, viruses are taken up through receptor mediated
endocytosis or membrane fusion; Membrane fusion occurs in enveloped viruses
--Eukaryotic Pathogenesis: Most fungi are saprophytes that feed off decaying matter;
Dermatophytes cause superficial infections of hair, skin and nails by producing
keratinases (eg ringworm, athelete's foot)
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323 The immune system: Innate immunity Ajay Gupta
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1 Anatomical barriers
2 Inflammation
3 Complement system
4 Cells of the innate immune response
o 4.1 Mast cells
o 4.2 Phagocytes
 4.2.1 Macrophages
 4.2.2 Neutrophils
 4.2.3 Dendritic cells
o 4.3 Basophils and eosinophils
o 4.4 Natural killer cells
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323 The immune system: Antigens and antibodies Ajay Gupta
Immunogen – a molecule that specifically interacts with an antibody or lymphocyte and
an immune response
Antigenic determinants (epitopes)
Proteins and polysaccharides induce a strong response
Lipids and nucleic acids often do not induce a strong response
Substances of less than 10,000 molecular weight are usually not antigenic
Antigens are large molecules, but recognition is based on discrete regions of
about 10 amino
acids or similar structural domains
Antibody Structure
Antigen binding (Fab) site (ab = antigen binding)
Fc region (c = crystalized)
Fab and Fc are functional regions defined by enzymatic digestion
Heavy chains and light chains (two of each define structure)
Constant regions (Fc)
elicits
Variable region (defined by Fab), however note that the Fab fragment also contains
structurally
constant regions
Immunoglobulin Classes
IgM (pentamer) – first class produced
IgG (monomer) – 80-85% total serum Ig; secondary response. Gamma globulin.
IgA (dimer in secretions) – secreted Ab; mucosal immunity. Not in serum and is secreted
outside the body.
IgD (monomer) – minor Ab involved in development.
IgE (monomer) – bound to basophils and mast cells, important in elimination of parasites,
allergies
Protective Outcomes
Neutralization – Abs stick to virus or toxin to block cell
binding
Immobilization and prevention of adherence – Abs stick to pili
and flagella
Agglutination and precipitation – bivalent Ab structure
permits long range cross
linking of Ag
Opsonization – Fc receptors on phagocytes bind Fc region of IgG bound to microbial
surface
Complement activation – Fc regions of IgG and IgM bind complement proteins and
activate
Antibody-dependent cellular cytotoxicity (ADCC) IgG bound to
cell is target for
NK cells,
which have receptors for IgG Fc region
323 The immune system: Humoral immunity Allen Prier
o
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humoral immunity– extracellular antigens
involves the use of B cells;
-B cells develop in the marrow
B cells proliferate and differentiate into:
§ Plasma cells
· antibody factories
· short-lived
· Abs bind antigens, provide protection
§ Memory cells
· long-lived
respond quickly upon re-exposure to an Ag
323 The immune system: Cellular immunity Allen Prier
o
o
o
o
cellular immunity – intracellular antigens
involves T cells
T lymphocytes
- T-cytotoxic cells – attack intracellular pathogens
- T-helper cells – orchestrate responses, specifically for B cells
T lymphocytes have T cell receptors
- functionally analogous to B cell receptor
- permits specific antigen recognition
- recognizes Ag presented on surfaces of host cells
- instead of Y-shaped Ab/immunoglobulin, has only two straight α and β strands
T cell clones differentiate into effector T cells
- second signal from dendritic cells
- some T cells form memory cells
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323 Diseases of the immune system: Immunization, vaccines and
immunological testing Kristy Roberts
Herd immunity – inability of pathogen to spread when no hosts are available – like what happened to
polio in USA
Viral vaccine development hampered by:
1.
Evasion of host immune system (HIV)
2.
Multiple genetic strains (flu)
3. Weak immune responses (common cold)
Vaccines - Types
· Antitoxin Þ Ab against specific toxin
· Antiserum Þ serum w/ protective Ab – usually impure
o Immune serum globulin Þ usually a passive immune, IgG and is pooled from blood
serum of several donors
Hyperimmune globulin Þ donors w/ high levels of specific Abs
Toxoids Þ inactivated toxins, NO symptoms but still get an immune response
Protein subunit Þ key protein Ag so unwanted side effects ¯
Polysaccharide Þ T-independent Ag which have NO memory cells so you add a protein (thus
conjugated vaccine) to make it T-dependent; ex. H. influenza type b (meningitis) & S.
pneumoniae
Adjuvant Þ insert materials that would cause immune response (flagellum, cell wall) that will
stimulate Ag but not infect – induce inflammation and causes Ag aggregation & precipitation to
facilitate phagocytosis
Attenuated Þ weakened form of disease causing agent, replicates causes mild disease b/c it
mimics wild type strain; CAN cause disease in immunocompromised by reverting to pathogenic
form
o
Sabin (polio) Þ 1960; safe but polio virus can spread causing vaccine; given orally for
mucosal immunity (so it can’t enter nervous system) – primarily producing IgA & some
IgG
Inactivated Þ UNABLE to replicate; requires boosters for amplification; used for viruses where no
natural safe counterpart exists
o
Salk (polio) Þ 1950; NO herd immunity & require multiple injections; IgG
o
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·
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Bacterial Vaccines
·
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Toxoid Þ see above; effective against diphtheria and tetanus
DTP combo Þ 3-in-1!! Diphtheria, tetanus & pertussis (which is not presented as acellular –
DtaP)
Polysaccharide Þ for encapsulated bacteria to elicit complement fixing Abs for surface
polysacchs; ex. Pneumococcus, salmonellae, meningococci, H. influenzae, E. coli, Klebsiella
pneumoniae, B. fragilis
Monoclonal Abs
·
·
·
High $$ Þ 18 MAbs approved for use w/ $5-6 billion in revenue
3 anticancer via Genentech Þ Herceptin (breast cancer), Avastin, Rituxan
Problems + solutions:
o
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Removal of inappropriate Ab Þ SINGLE mouse Ab
Mouse MAbs immunogenic Þ mouse variable region fused to human constant (HAMA)
Rituxin & Remicade cause allergic rxns Þ insert mouse complementary- determining
regions into human Ab (90-95% human) fewer HAMA responses
Humanized MAbs technically demanding, reduced Ag affinity Þ (a) change the mouse
like xenomouse & HuMab-Mouse or (b) skip the mouse! (in vitro phage
323 Diseases of the immune system: Type I, II, III, IV Hypersensitivities
Kristy Roberts
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·
·
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Type I: allergies, anaphylactic shock. IgE mediated/ sensitized mast cells. Mast
cells synthesize prostaglandins and leukotrienes from arachadonic acid.
A. Localized anaphylaxis: normal inflammation. Ex. Hives, hay fever,
asthma
B. General anaphylaxis: more severe. Ex. Bee stings, peanuts, PCN
Type II: transfusion reactions, hemolytic diseases, cytotoxic. IgG mediated
Type III: rashes, joint pain, immune complexes. Immune complex mediated.
A. Ex. Farmer’s lung, rubella, streptococcus pyogenes
1. Arthus reaction: local reaction in response to injected antigen
2. Serum sickness: passive immunization with animal serum
Type IV: delayed cell mediated (insect venom, tuberculosis), contact dermatitis
(poison ivy, nickel), transplant rejection, tuberculin reaction
323 Diseases of the immune system: Autoimmunity Negin Sovaidi
Autoimmune
Disease
What it Affects
Hypersensitivity
Type
What Happens
Graves’
Disease
Thyroid
II
Auto-Ab’s bind to TSH receptor;
hyperthyroidism
Myasthenia
gravis
Muscles
Nervous system
disease
II
Auto-Ab’s bind to ACh
receptors on muscle; prevent
muscle contraction; can cross
placenta via IgG
Insulindependent
Diabetes
Islets of Langerhans
(pancreas)
II, IV
T-cell destroy pancreatic cells;
antagonist of insulin receptor;
hyperglycemia, ketoacidosis
Hemolytic
Anemia
Red blood cells
Rheumatoid
Arthritis
Widespread, esp.
joints
Lupus
Widespread
II
III, IV
III
Ab, complement, and
phagocyte destroy of RBCs
Immune response to collagen in
joints
Auto-Ab’s to DNA and other
(glomerulonephritis,
vasculitis, arthritis)
components of nucleus form
immune complexes in small
blood vessels
Goodpasture’s
Syndrome
Basement Membrane
(non-collagenous part)
II
Auto-Ab’s specific for type IV
collagen react with basement
membrane of kidney glomeruli;
results in gomerulonephritis;
pulmonary hemorrhage
Celiac Disease
Lining of Small
Intestines
IV
Unable to tolerate gluten;
malabsorption of nutrients,
atrophy of intestinal walls
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323 Diseases of the immune system: Immunodeficiency Negin Sovaidi
Immunodeficiency
Disease
Primary or
Secondary?
What it Does
SCID
Primary
No B or T cells; very rare
Causes: faulty RAG genes, IL-2 receptor
gene can’t receive signal to proliferate; lack
of adenosine deaminase, needed for B, T
cell proliferation
Agammaglobulinemia
Primary
No antibodies; very rare
Arrested B cell development
X-linked gene; affects coreceptor btk protein
(Bruton’s tyrosine kinase)
Selective IgA
Deficiency
Primary
Most COMMON immunodeficiency
Little or no IgA; no mucosal immunity
Results in weaker immune system (IgG takes
over role)
X-linked IgM Syndrome
Primary
X-linked; cannot fully activate B cells; can
produce IgM but no class switching; no
cytokines to form germinal centers; T-helper
problem
DiGeorge Syndrome
Primary
Failure of thymus development
No T cells
Leukocyte Adhesion
Primary
Phagocyte defect
Deficiency
WBCs fail to localize mutations in integrins,
etc.; cannot home in on inflammatory tissue
or back to lymph nodes
Chediak Higashi
Disease
Primary
Phagocyte defect
Lysosomal failure to fuse; granulomas form
Chronic Granulomatous
Disease
Primary
Phagocyte defect
Phagocytes fail to produce oxygen radicals;
cannot kill bacteria (faulty ROS)
MHC Class II
Deficiency
Primary
Possible cause: failure to make CLIP protein
Many Complement
Deficiencies
Primary
Any one of the 20+ proteins could be
defective
AIDS
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Secondary
Late stage of HIV disease
Infects immune cells (T-helper cells,
macrophages)
Causes secondary infections
AIDS-related complex= Hairy leukoplakia
(latent Epstein-Barr virus) [tongue pic]
Epidemic; fatal disease; treat with AZT
325 Properties of Matter and Energy: Microscopic Potential Energy
 Properties of Matter and Energy: Microscopic Potential Energy
Microscopic Energy – energy of the microscopic level.
We want to focus on Potential energy, which has to do with interactions of molecules.
Potential Energy – controls the interactions between molecules or atoms, it can be
repulsive or attractive.
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e.g.) cellular bioenergetics
ATP  important energy source for coupled reactions, energy is released to make
another molecule that requires energy. Phosphate bonds in ATP are referred to as high
energy bonds. When ATP  ADP + P, there is a release of 7.3 kcal/mol of energy.
e.g.) interactions between molecules in a biological system
Receptors
Acted upon by endogenous materials (molecules present in that organism like DNA and
sugars). Exogenous or Xenobiotics are foreign to the environment such as benzene
which is not a natural component of the organism. Drugs that act at a specific sites are
called target sites. Normally the target molecules are macromolecules (polymers) like
nucleic acid polymers (RNA and DNA) and amino acid polymers such as proteins.
There are two types of proteins: structural and regulatory proteins.
Structural Proteins - make up frame work of the body.
Regulatory Proteins – function to regulate some process in the body.
There are 4 major categories of macromolecules and regulatory proteins.
1) Enzymes – are proteins that act to catalyze chemical reactions in the body to
accelerate the chemical process or reaction.
2) Carrier molecules – molecule that acts to transport other molecules to other parts of
the body. e.g.) transferring is a carrier in the body for iron.
3) Ion Channels – proteins that serve as channels to let ions pass through the
membrane.
4) Receptors – Macromolecules that upon activation mediates a physiological
response. 2 types- intracellular and outer surface of membrane.
Ligand – molecules that bind to receptor site.
Agonist – when a ligand activates the receptor
Antagonist – when a ligand does not activate the receptor but still binds to a receptor
having no effect.
Reverse or inverse agonist – produces the opposite effect of an agonist
Conformational Change – change in the 3-d structure of that protein when ligand binds to
Receptor
7 Transmembrane Protein – the peptide chain passes through the membrane 7 times. The
peptide chain in the lipid bilayer are in the form of alpha-helices.
Acetylcholine receptor – can bind to nicotine and to muscurane.
Nicotinic receptor – ligand gated ion channels; if ligand is bound, channel opens and ions
can flow; if ligand is not bound channel is closed and ions can’t flow.
Stochastic Process – interaction of 2 molecules determined by probability (based on
Statistics)
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325 Properties of Matter and Energy: States and Properties of Matter
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Properties of Matter and Energy: States and Properties of Matter
3 different states of matter
-fluid
-solids, which have relatively few interactions occur in solid state; fairly inert (this was not
covered as much in lecture)
-liquid crystals
FLUIDS
Fluids are shapeless which means it can be sheared due to series of layers of molecules and the
rate of layers can be different (fastest in the center and slowest outward towards the walls) and
molecules are independent of each other.
Omni directional pressure – pressure pushing back is in all directions even if you apply a force to
the system in one direction.
Possess Viscosity – as resistance of a fluid to flow, higher the value and the more viscous so they
have a greater resistance to flow. Units => poise (H2O = 0.1) (blood = 0.4)
No Slip Condition – fluid that flows adjacent to a solid surface, molecules at surface have no
velocity.
Subject to turbulence – first of all laminar flow is everything flowing in a single direction and
any disruption in the layers, other then linear, is turbulent flow.
SOLIDS
Solids are highly ordered structure of atoms forming a crystal lattice known as a crystalline
structure.
LIQUID CRYSTALS
Liquid crystals are an intermediate between liquids and solids. Molecules are free to move but it
is still highly ordered in a structural array. Example is your lipid bilayer.
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325 Properties of Matter and Energy: Thermodynamics Derek Philips
Thermodynamics - the study of the effect of changes in temperature, pressure, and
volume on physical systems at the macroscopic level by analyzing the collective motion
of their particles
Chemical thermodynamics- the study of energy changes during chemical
transformations
Laws of Thermodynamics
-First law of thermodynamics: The total amount of energy in the universe is constant
(Matter cannot be created or destroyed)
- Second law of thermodynamics: The disorder of the universe always increases. (all
chemical and physical processes occur spontaneously only when the reaction
increases the disorder of the universe)
-Third law of thermodynamics: As the temperature of a substance approaches
absolute zero (0K), disorder approaches zero.
Thermodynamic Systems
- Open System: Matter and energy are exchanges between the system and its
surroundings (ex: living organisms)
-Closed system: only energy can be exchanged (ex: greenhouse)
-Isolated system: The system does not exchange heat, work, or matter with the
environment (ex: isolated oxygen cylinder)
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325 Chemical Kinetics: Orders of reaction Annie Hahn
a. Reaction order determined experimentally
b. First order:
i.
Drug C à Drug D
ii.
Rate = -dc/dt = k[C]
1. k = rate constant
2. C = concentration of drug at any given time
iii.
If you take natural log of equation: graph is straight line
a. C0 = initial concentration
iv.
Half-life (T1/2): Time required for concentration to decrease by 50%
T1/2 = 0.693/k
Unique characteristic: time for 50% change is the same (don’t need to know initial
concentration)
c. Zero order:
.
Drug C à Products
(Therefore, concentration is negligible)
i.
-dC/dt = k
ii.
Half-life: t1/2 = 0.5C0/k
Need to know initial concentration
d. Second Order:
.
Drug C + Drug D à Products
i.
–dD/dt = k [C][D]
e. Apparent First order
.
If there are two drug components that make up the product and one is
fairly constant in concentration, then it will have a constant concentration.
Example: [OH] of esters is constant at constant pH.
i.
Therefore, second order reaction becomes an apparent first order
reaction
ii.
Example using esters:
ROOR + OH- à ROOH + ROH
Rate = d[ROOR]/dt = k[ROOR][OH]
If [OH] = constant, then new rate constant
. k* = k[OH] and rate equation transforms to à
a. Rate = d[ROOR]/dt = k* [ROOR]
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325 Chemical Kinetics: Rates and rate constants Annie Hahn
a. Reaction rate is proportional to the number of collisions and drug
concentration
i.
Increasing in either category will increase the rate
b. Reaction rate is never constant due to decreasing drug concentration
over time due to decomposition
.
Fastest at the beginning of
i.
the reactionRate = -dA/dt = k [A]a [B]b
ii.
k = rate constant
iii.
iv.
a = order with respect to drug A
b = order with respect to drug B
c. Explains how rate changes as concentration changes over time
d. Overall order = sum of exponents of concentration terms (a+b+c…)
e. Rate constant: speed of a chemical reaction
.
Zero order:
k = concentration/time
i.
First order:
k = 1/time
ii.
Second order:
k = 1/(time * concentration)
325 Chemical Kinetics: Stabilization Melanie Nguyen
To prevent the following:
o
o
Hydrolysis
 Limit the water present – remove some of the water. Ie make it an elixir,
replace water with alcohol
 Prepare drug as a suspension (solid particles suspended in liquid vehicle),
keep some drug out of solution by keeping it in solid form.
 Drug is reconstituted. Packaged in a container in dry form (all of drug and
excipients, more stable in solid form). When it’s time for patient to receive
drug, solvent system is then added.
 Can be reconstituted as solution or suspension. Reconstitution does
not have to mean suspension
 Control the pH. Product is buffered using excipients to most stable pH.
 Make it solid. Solid is more stable
 Refrigerate product (temperature)
 Complex formation of drug and something else. Complex may be more
stable.
Oxidation
 Packaging: protect from light
 Lower temperature (generally not as important for oxidation reaction as it is
for hydrolytic reaction)
 Exclude oxygen by putting in some inert gas like nitrogen (Purge the oxygen
with nitrogen, displace it). Only works for drugs in single dose container:
packaged in a container that only has 1 dose for the patient. Especially single
dose injection
 Excipients
 Chelating agents: will tie up trace metal ions. Binds metal ions so they
are not available to initiate the oxidation process. Ie EDTA, citric acid
 Antioxidants
o Reducing agent – reduces the oxidized drug back to original
form (not very common) ie sodium thiosulfate
o
Agent preferentially oxidized (oxygen scavengers):
antioxidizing agent is more easily oxidized than drug molecule.
Antioxidant goes through oxidation and the drug doesn’t.
 Sodium bisulfite
 Significant percent of population have allergies
to sulfites, resulting in antiphylactic effect.
 Ascorbic acid
o Chain terminators: will stop propagation process
 Cysteine, thioglycerol (if drug is water soluble)
 BHA, BHT, propyl gallate (in topical ointments),
alpha-tocopherol (vitamin E) - (if drug is lipid soluble)
o
o
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Racemization
 Reduction of temperature (refrigeration)
 Adjust pH (reaction slower/faster at different pH)
Photolytic
 Packaging (amber-colored vials: protect from light)
325 Chemical Kinetics: Energy of activation Melanie Nguyen
 Energy of Activation
 Energy barrier that has to be overcame when two molecules collide in order for
reaction to proceed
o A catalyst is used to lower this energy requirement; therefore, speeding up the
rate of reaction
Disperse systems: Particle movement
8. Disperse Systems: Particle Movement
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Recall: Any kind of disperse system has to have 2 components = a binary system.

Note: The smaller a particle is, the faster it moves, in any system.

Random walk: The staggering of molecules of a system that occurs by chance. (Note
that all molecules are doing random walk.)
A. 1-dimensional random walk

Definition: The movement of a particle along a single axis.

Rules for random walk as follows:
1. Each molecule or particle moves throughout the system by taking steps at a
defined distance. Each step = delta.
2. For each step the molecule can either go left or right, and there is an equal
probability for either direction.
3. Each particle moves independently of the others.
4. Each molecule or particle moves with a velocity = v.
B. Diffusion


Diffusion is the single most important transit system for heat and mass.
Diffusion is NOT the movement of particles from a higher concentration to a lower
concentration.

Recall: The rate of diffusion is dependent on size of particles.

Particles diffuse slower than molecules.

Diffusion is constantly occurring in all molecules, unless in a fixed crystal (solid state.)

Recall that, the time (t) for a molecule to diffuse a distance (x) is proportional to the
square of that distance.
t = x2
2D
Where t = time, x = distance to diffuse, and D = diffusion coefficient (constant)
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325 325 Disperse systems: Solutions - introduction and properties
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Disperse Systems: Solutions – Introduction and Properties
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 Dispersed system = One substance (dispersed phase) is distributed in discrete units
throughout a second substance (continuous phase, dispersion medium, or vehicle). Size
ranges from atomic/molecular size to large (mm).
 Classification of dispersed systems depends on (1) physical state and (2) size of
dispersed particles (see below):
1. Physical state:
a. liquid-gas (inhaler, aerosol)
b. liquid-liquid
c. solid-liquid (suspensions)
d. etc.
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2. Size of dispersed particles
a. Molecular dispersion = Less than 1 nm; homogenous
b. Colloidal dispersion = 1 nm to 1 micrometer; homogenous or
heterogeneous
c. Coarse dispersion = Greater than 1 micrometer (i.e. suspensions)
 Solution: A mixture of 2 or more components to form a homogenous molecular or
ionic dispersion
 Note: In a solution, distribution of the components is uniform throughout the
mixture.

Binary solution: Composed or 2 parts. (1) Solvent and (2) solute (see below):
(1) Solvent
a. Usually larger in amount than solute
b. Generally a liquid; most common solvent is water because it is the safest
(2) Solute
a. In pharmaceutics, the solute is usually the drug.
325 Disperse systems: Solutions - Colligative properties Amy Brotherton
Colligative properties are properties of solutions that depend on the number of
molecules in a given volume of solvent and not on the properties/identity (e.g. size or
mass) of the molecules. Colligative properties include: relative lowering of vapor
pressure; elevation of boiling point; depression of freezing point and osmotic pressure

Effect on vapor pressure
Graph goes up to the right: pure solvent
As u increase temperature, causes more water molecules to
vaporize and escape into vapor phase which causes an
increase in vapor pressure
Where vapor pressure = atmospheric pressure, liquid
begins to boil
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When u dissolve nonvolatile drug into water, where would the curve be?

It would be shifted to the right
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At any given temperature, the vapor pressure will be lower for the solution rather than the
pure solvent: colligative property (vapor pressure lowering) depends upon number of
things

If u compared a one percent solution to a 5 percent solution, a greater number of particles
results in further lowering of the vapor pressure; so the 5 percent solution will be shifted
even more to the right.
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Effect on boiling point - - would boiling point be different for solution from solvent?

A solution will boil at a higher temp than pure solvent, there are more particles in
solution.

Effect on freezing point – freezing point will be lower for a solution than for pure
solvent

The point of putting antifreeze in your radiator is so it will have to be colder to make it
freeze
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Osmotic pressure – how much pressure is required to prevent water from diffusing
across the membrane

Why do acids, bases and salts produce osmotic pressures much greater than expected?

Ions dissociate, have twice as many particles, each mole of NaCl produces two moles of
particles
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Iso-osmotic versus iso-tonic –

Iso osmotic means equal osmotic pressure, implies that the semipermiable membrane is a
“perfect semipermeable membrane only allows solvent to cross not solute…iso tonic
refers to osmotic pressure across a LIVING membrane (like a red blood cell) difference is
that semipermeable membrane is not a “perfect” semipermeable membrane, might allow
solute and solvent to cross
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If a solution is isoosmotic does that also mean it is isotonic?

No.
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Why do we care about osmotic pressure in drug delivery?
We want it to be isoosmotic.

Isotonic solution is always isoosmotic, an isoosmotic solution is not always isotonic

.9% NaCl is isoosmotic and isotonic
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325 Disperse systems: Methods of Modifying Interfacial Phenomena
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Disperse Systems: Methods of Modifying Interfacial Phenomena
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A. About Surface Interactions:
 Interface-any time that have more than a single phase (example liquid and solid)
have an interface.
 The boundary between two phases effect the behavior of the system
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Example: Absorption of the drug between the body/GI (cell membrane)
and drug (contents)

Characteristic of each type of system-stability or destabilizes.
Interfacial Phenomena
 Liquid interface properties-one component (not both) as liquid
 Surface Tension-surface properties of a liquid when in contact with a gas
 A property of the interface not of the liquid-if you change either component you can
change the surface tension.
Example: Water droplet:
 A-Equal forces in all directions-surrounded by like molecules.
 B-Surface tension-the force you have to apply at the surface of a liquid to
counterbalance inward pull of liquid molecule
 Interfacial tension-analogous with surface tension except interface between two
liquids.
Example: Water and CCl4 (two immiscible liquids that do not mix with
each other.
** Immiscible because molecules within a phase has greater attraction
than between phases.
 Adhesive forces-between molecules of two different phases
 Cohesive forces-between molecule of same phase.
 Immiscible- when the sum of the cohesive is greater than the sum of the adhesive
forces. (i.e. Water for self will push carbon tet. Out-separate layer)
 In general aqueous driven by hydrogen bonding for separation:
 The more unlike the two liquids/dis-similiar the greater the interfacial tension.
 Interfacial or surface tension-depends upon the two components in contact with each
other and the temperature
 Change one and will change the value.
 Solid-liquid interface-much different than liquid-liquid or liquid-gas, different
characteristic by solid being immovable.
C. Surface Free Energy:
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 Two dissimilar act in way to act to decrease contact with each other
~ Appear to be lowest energy
 So increase surface area of contact increase the free energy, decrease surface energy
then decrease free energy.
 Energy Change:
~w = äÄA
 w – surface free energy = work or amount of energy put into the system to increase
area by a quantity of Ä A.
 either + or – depending Ä A.
 A – surface area of contact
 Can either increase (+) or decrease (-)
 ä – surface area interfacial tension
 If you increase the area and will increase surface free energy.
 Want smallest A for the lowest free energy.
 Ä A increase doing work, w +, require energy input.
 Ä A decrease, w -, lower energy state, energy increase out of the system.
 ä= w/ÄA
 A measure of amount of (or given out if decease in Ä A) energy required to increase
the system to change the surface area of contact by Ä A.
 Doesn’t want to be a higher energy, so will coalesce back together, spontaneously
separate from one another and likes come together.
 What if you want a emulsion to stay? Example with creams, topical-somehow have
to stabilize them to don’t have to shake.
How do you stabilize?
 Stability = surface free energy.
 w = äÄA
~ With this only two ways to change the energy:
1. Decrease the surface area to increase stability
Ä is given value at temp, so change for that system.
2. Modify interface (can’t change ä) so decrease surface free energy is the
only possible way
3. Introduce another substance (solute).
d. Adsorption at Liquid Interface:

1.
Addition of another solute 3 things can happen:
Solute disperse evenly between two components
- even dispersion
-no effect on the interface
-rare-usually inert gases
2.
Substances could concentrate in the bulk of one of the liquid-avoiding the interface.
-negative adsorption (surface phenomena)
-surface inactive
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-Example: sucrose-concentrate in water (structure water more). Sometimes have
property of increasing interfacial tension, by increasing the structure of one of
the phases, making their attractive forces go inwards (more alien to the other)
3.
Solute molecules concentrate at interface.
-surface active
-positive adsorption

These have certain characteristics:
1. Ampliphiles-affinity for both polar and nonpolar-example phospholipids.
2. Reduce interfacial tension-aligning this way to decrease the tension between
the two liquids. This substance fools the interface to think associated with own
kind.
E. Type of Surfactants:
A. Wetting Agents- substances that allows displacement of air that is adsorbed to
the surface of solids. It allows contact between a solid and a liquid.
 Example-a fine powder on water-doesn’t really come into contact with water
because a fine layer of water is adsorbed to the surface of the power.
 Important in suspensions
 Coats the solid and more easily displaces air and allows liquid to make contact.
 HLB range 7-9
B. Emulsifying Agent-substances that reduce the interfacial tension between oil
and water (non-polar and polar).
 Good for stabilizing emulsions
 Act at surface between dispersed phase and continuous phase to reduce interfacial
tension.
F. Two types of emulsions:
1. Water in oil
 HLB value 3-6 give water in oil dispersion
2. Oil in water
 HLB value of 8-18 give oil in water dispersions
325 Disperse systems: Solutions - pH and buffers Jacob Mouchet
-Buffer
a. Mixture of weak acid and conj base (most pharm. drugs) or a weak base and its
conjugate acid; is a ratio
b. Must have 2 components, designed to prevent significant changes in pH of the
solution
c. pH can have an effect on stability (of drug)
-Ratio is Henderson-Hasselbalch equation: pH=pKa + log [base] / [acid]
a.
pKa = -log Ka
b. pH = pKa + log [b] / [a]
c. An equal ratio of base/acid makes the solution better at controlling the pH.
- Buffer Capacity: measure of the resistance to a change in pH
a. measured by the Van Slyke Equation:
i.
B = 2.3 C [H3O+] Ka / [H3O+ + Ka]^2
b. C is the sum of the concentrations of buffer components
c. B is buffer capacity
-Buffer capacity highest when pH=pKa and [acid] / [base] ratio is 1
a. A buffer is effective at + or – 1 from the pKa
b. The larger the B, the better the buffer. Measure of how good the buffer is.
i.
Buffer with .1 is ten times better than a
buffer at
.01
ii.
B and concentration ( C ) are directly
proportional,
increasing concentration
increases B
c. Depends on buffer concentration; B (buffer capacity) increases as
concentration of buffer components increases
-*Preparation of a buffer solution*
a. Select weak acid. Dependent on the pH of the solution you are trying to prepare
(useful range is pKa + or – 1)
iii.
Acetic acid pka (4.76)
iv.
Citric acid ( 3.15, 4.78, 6.4) 3 different protons
that
can be donated, proton lost most easily is
lower pKa
value
v.
Phosphoric acid ( 2.12, 7.21, 12.67) 3
different
protons as well
b.Calculate the ratio of base to acid component (H-H equation) for the pH you want,
already know the pKa from acid
c. Use Van Slyke equation to calculate total buffer concentration
vi.
Generally B of .01-.1 is adequate
d. Calculate the molar amounts of buffer components
e. Measure the pH
-The Henderson-Hasselbalch equation can be used to calculate:
a. The pH of a buffer solution when the base/acid ratio is known
b.The base/acid ratio that is required to give a buffer of a specific pH
c.The pH change resulting from the addition of an acid or base to a buffer solution
-Why would we use buffers in pharmacy?
a. Influence drug solubility
b. Affect drug absorption into body
c. Improve drug stability
d. Decrease tissue irritation
If buffer capacity is too high it can cause the biological pH to change
a. Patients can get large amounts of 5% dextrose without affecting pH. Why?
i.
Dextrose is not a buffer.
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326 Dosage Forms: Excipients Joanne Nguyen
Binders: imparts cohesiveness to the tablet formulation
Starch, gelatin, povidone, natural and synthetic gums
Lubricants: prevents adhesion of powder to surfaces of dies and punches and
may improve flow
Magnesium stearate and talc
Excess lubricant may result in poor disintegration or delayed dissolution
Glidants: Improve flow characteristics of powder
Colloidal silicone dioxide or talc
Disintegrants: Facilitate the breakup of tablet after administration eg. Starch
Super disintegrants: effective at low levels eg. Croscarmelose, crospovidone,
or sod starch glycolate.
Colorants: useful to distinguish one dose from another and aesthetic appeal
Only approved and certified water soluble FD&C dyes, mixtures, or
corresponding lakes used.
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326 Dosage Forms: Tablets Brandon Shook
Tablets are solid dosage forms, available in different shape & sizes. They are usually prepared by
compression of the drug with several excipients. Tablets may be scored for fairly accurate breaking. 4
types - Immediate Release Tablets, Sugar-Coated Tablets, Film-Coated Tablets, Enteric-Coated Tablets;
Types of compressed tablets = 1. Multiple Compressed Tablets A. Layered Tablets B. Press-coated
Tablets 2. Chewable tablets 3. Controlled release tablets. Rapid dissolving tablets (RDTs) =
disintegrate/dissolve in about 15-30 seconds in the mouth. Tablet triturates are molded tablets. Oral
thin films = thin, flexible oral strips made of water soluble polymers which release any active ingredients
immediately in oral cavity. Lozenges aka troches = localized effects. Vaginal tablets. Lollipops = controls
breakthrough cancer pain and lasts about 15 minutes.
Two punches + One die = 1 Station. Concave Punches = Convex Tablets. Tablet weight and thickness is
controlled by the amount of die fill and compression pressure. Tablet machines may be single station or
rotary presses. 1. Granulation fills die cavity as lower punch drops. 2. The Upper punch then lowers and
compresses the material into a tablet. 3. Upper punch finally retracts and lower punch rises to eject the
tablet.
Diluents - provide bulk to make the tablet a practical size for compression. lactose, microcrystalline
cellulose, dicalcium phosphate, powdered sucrose
Binders - imparts cohesiveness to the tablet formulation. starch, gelatin, povidone, natural and
synthetic gums
Lubricants - prevents adhesion of powder to surfaces of dies and punches and may improve flow.
magnesium stearate, and talc
Glidants - improve flow characteristics of powders. colloidal silicone dioxide or talc
Disintegrants - these facilitate the breakup of tablet after administration, e.g., starch
Colorants - colors are useful to distinguish one dose from another, and provide aesthetics
Three methods to making tablets - Wet Granulation Method, Dry Granulation Method, and Direct
Compression. Granulation is done so that powder can flow evenly & freely from the hopper into the
dies. Wet Granulation = 1. binding agent added 2. damp massed screened 3. drying 4. dry screening 5.
lubrication 6. compression. Dry Granulation = Used when drug is moisture- or heat-sensitive and/or
powder has cohesive properties. Direct Compression = Some drugs/excipients possess free flowing &
cohesive properties so that granulation is not required. Potential Problems = capping or splitting,
lamination, reduced disintegration and/or dissolution.
Tablet Coating - Protect from air/moisture, Taste masking/Identification, improve product appearance,
Sustained Release/Enteric Coatings. 3 types of tablet coating = 1. sugar coating 2. film coating 3.
compression coating. Sugar coating = Multistep process involving sealing, subcoating, smoothing, color
coating, polishing & printing. SHELLAC. Film Coating = This preferred method applies a thin, uniform
coating on tablets. Formulation contains polymer, plasticizer, colorant, and solvent. Coating problems =
pickling and peeling, orange peel effect, mottling, bridging.
Packaging and Storage = Store in tight containers at low humidity and away from temperature extremes.
Add desiccant packet (e.g., silica gel) or use light-resistant containers if needed. All dosage forms must
be taken with water. Quality Control = 1. tablet hardness 2. tablet friability 3. tablet thickness 4. tablet
weight 5. content uniformity 6. disintegration test 7. dissolution test. Coating or sustained release
tablets should not be crushed or chewed
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326 Dosage Forms: Suppositories Roger Lee
Suppositories - Review
 Solid dosage forms used for insertion into body orifices for either systemic or
localized effects (very few dispensed, mostly for babies or those who can’t swallow)
o Rectal, vaginal (pessaries), urethral (bougies)
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 Advantages – bypass harsh GI, avoid 1st pass metabolism, won’t irritate stomach
 Disadvantages – Erratic absorption depending on physiologic and physiochemical
factors
 2 types: fatty/oleaginous(oily) like cocoa butter base versus water miscible like
glycerinated gelatin or polyethylene glycol bases
 Made by melting into mold, compressing them into shape or hand rolling them
Wt of drug
o Density factor = -----------------------------------Wt blank suppository – wt of medicated suppository + wt of drug
 Common Uses:
o Rectal – pain, migraines, tranquilizers, laxative, hemmoroidal
o Urethral-for ED (like Viagra but inserted not swallowed)
o Vaginal-for infection or contraception
326 Drug Delivery Systems: Controlled Release Indu Shekar
Controlled Released Dosage Forms
CRDF—a dosage with the drug release kinetics is predictable and reproducible from one unit to
another. Can have local or systemic effects. Routes of admin: oral, transdermal, intervenous,
intrathecal, subcutaneous, vaginal.
Terminology:
modified release—drug release accompanies therapeutics.
extended release—allows reduction in dosage frequencies.
delayed release—drug is released at a time other than promptly after administration.
targeted release—describes drug released directed toward isolating or concentrating a drug at a
specific site.
Conventional vs. Controlled Release
Conventional
--drug concentrations fluctuate widely
--multiple dosing
--may cause non compliance
--predominant
Controlled
--constant drug level with narrow fluctuation
-- once or twice daily dosing
--control rate of release and/or target specific site (eg. GI tract)
--gaining increasing popularity
Advantages of Controlled Release
-- improvement of patient compliance
-- usage of less total drug
-- improvement in treatment efficiency
-- reduction in cost
Disadvantages of Controlled Release
-- dose dumping and delayed onset
-- dependent on residence in GI tract.
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-- loss of flexibility in adjusting the drug dose or dosage regimen
-- high cost due to new technology and obtaining govt approval
Polymers in Controlled Release Dosage Forms
- Matrix system
- Drug substance and a polymer excipient are mixed to form a homogenous system.
- Diffusion occurs when the drug passes from the polymer matrix into the external
environment.
- Release rate decreases along the release.
- Membrane system
- a reservoir—whether solid drug, dilute solution, or highly concentrated drug solution within a
polymer matrix—is surrounded by a film or membrane material (polymer).
- the coating membrane controls the release of drug.
- nearly zero- order release kinetics.
- Swelling-controlled release system
- swelling-controlled release systems are initially dry and when placed in the body, will absorb
water or other fluids and swell. Hydrogels polymers that will swell without dissolving when
placed in water or other biological fluids
- Biodegradeable system
- materials degrade within the body as a result of natural biological processes.
- eliminate the removal of a drug delivery system
- hydrolysis of the polymer chains.
Candidates for Oral CRDF:
- drugs with appropriate half-life (2-8 hours)
- drugs without extensive first-pass clearance
- drugs that are uniformly absorbed from GI tract
- drugs with small dose (<500 mg)
-drugs with a good margin of safety
- drugs used in the treatment of chronic conditions.
Classification of oral CRDFs
Dissolution/Diffusion-controlled release
Dissolution-controlled release
- drug release is controlled by the dissolution rate of a drug in the GI medium.
Diffusion-controlled release
- the drug release is controlled by the diffusion of the drug molecules.
Generally, these two mechanisms are present in the same dosage forms.
-microencapsulated drug: drug release dependent on the permeation through the membrane
wall. Different rate of drug release may be obtained by changing the ratio of core to wall, the
polymer used for encapsulation and method of microencapsulation.
- coated beads, granules and microspheres: thickness of coating controls the rate of drug
release.
- matrix dissolution control: the drug is distributed in an insoluble polymer matrix. The rate of
drug release is controlled by the rate of penetration of the dissolution fluid into the matrix.
Different drug release rate can be achieved by the different porosity of matrix.
- Embedding the drug in hydrophilic matrix system:
- tablet is wetted by gastric fluid and the polymer begins to hydrate.
- as water penetrates further into the tablet, the thickness of gel layer increases and
soluble drug diffuses through the gel layer
- Embedding the drug in inert (hydrophobic) matrix system
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- drug is released by diffusion.
- polymer will retain its shape during leaching of drug and will be excreted with feces.
Ion-exchange resins
- Water-insoluble materials (polymers)—backbone
- Ion functional groups
- anion exchange resisn—amino group, quaternary ammonium groups
- cation exchange resin—carboxylic groups, sulfonic groups
- Prolongs and sustained release over 8 to 12 hours into the GI tract
- Drug release: pH, electrolyte, property of resin.
- Increase stability of the drug by protecting from hydrolysis or degradative enzymes, improve
palatability of the formulation
Osmotic Pumps
- Release of drug: water enters into the core tablet, drug dissolves, and then drug solution is
pumped out through the orifice due to the osmotic pressure
- Zero-order release and higher delivery rate than solution-diffusion mechanism.
- Tablet remains intact and is eliminated in the feces.
Gastroretentive Systemsprolong the gastric residence time
- Approach: density < gastric fluid (hence the floating) and effervescent system.
- Hydrodynamically Balanced System (HBS)
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326 Drug Delivery Systems: Transdermal delivery Indu Shekar
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Transdermal Controlled Delivery Systems designs
Membrane-controlled system
1. Adhesive
2. The rate controlling membrane
3. Drug reservoir
4. Backing (FFS material)
-
Constant rare of drug delivery
-
Great margin of safety for the drug with narrow therapeutic index
-
Lesser degree of patient-to-patient variability
-
Detrimental to comfortable wear
Matrix System
1. Adhesive
2. Backing
-
Thin, elegant and comfortable to wear
-
Preferred for drugs with very low skin flux
-
Stability issues (may crystallize or agglomerate)
-
A non-constant rate of drug delivery
Controlled Implantable Drug Delivery Systems
Norplant
- a contraceptive implant
- a 5-year implant by Wyeth-Ayerst
capsule: does not release as much drug initially
matrix: releases a lot initially
membrane-covered rod: most constant
Duros Implants
- miniature
- osmotically driven
- long-term
-parenteral
- constant rate of delivery
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326 Drug delivery systems: Ophthalmic Delivery Linda Cheng
Ophthalmic Dosage forms
·
Ophthalmic preparations must be sterile
·
Come in solutions, suspensions, ointments, and ophthalmic inserts
·
Can be used for anti-inflammatory, antibiotics, vasoconstrictors (used to treat red-eye), and
miotics (used to dilate pupils)
·
One drop contains about 50-75 mcl; eye only holds about 10mcl; most fluid is lost via
nasolacrimal drainage
·
Typical packaging is in a multi-dose container (contains preservatives)
Wash hands before use and administer by tilting the head back and without letting the
dropper touch the eye
Ophthalmic Solutions
·
Isotonicity value: 0.6-2.0 % NaCl or its osmotic equivalent
·
Buffers & pH: Ideally, formulate at pH 7.4 (pH of tears in the eye). Keep buffering capacity
low
·
Viscosity & Thickening Agents: increasing viscosity increases contact time with the eye.
HPMC and methyl cellulose are thickening agents.
·
Ocular Bioavailability: Increase bioavailability by
o
Increasing proportion of unionized drug (unionized form absorbs better)
o
Increase viscosity (increases contact time with the eye and decreases loss via lacrimal
drainage)
Other Ophthalmics
·
Ophthalmic suspensions
o
Suspended particles < 10 µm; shake before use
·
Ophthalmic ointments:
o
Needs to be non-irritating and permit drug release
o
Packaged in a tube ≈ 3.5g
o
A ribbon of medication is placed directly into the lower lid, apply at bedtime (due to blurry
vision)
·
Ophthalmic inserts
o
Increases contact time with the eye
o
e.g., pilocarpine (Ocusert; 20 or 40 μg/hr over 7d) – used to treat glaucoma
o
Contact lens is an example of an ophthalmic insert
Types of Contact Lenses
·
Soft – most used (comfortable); made from hydrogels (such as hydroxyethyl methacrylate
(HEMA)) and silicone hydrogels
·
Hard – did not allow oxygen permeability
·
Rigid gas permeable (RGP) – did not sit well in the eye
Uses for Contact lenses
·
Corrective contact lenses
·
Cosmetic contact lenses
·
Therapeutic contact lenses (pilocarpine – Ocusert)
Contact Lens Solution
·
Solutions you use to take care of your contact lenses
·
Multipurpose – for both rinsing and storage of lenses
·
Enzymatic cleaning, disinfection and neutralization
o
Thermal or chemical
·
Prevents microbial contamination and protein adhesion to hydrogel lenses
Proper Uses of Lenses
·
Wash hands
·
Use proper solutions for cleaning and storage
·
Need to consider how drugs may affect lenses (drugs may increase or reduce tear
production, rifampin stains contact lenses orange)
Transscleral iontophoresis – delivers drug to posterior segment of the eye
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326 Drug delivery systems: Aerosol Delivery Linda Cheng
Aerosols
Alveolar lining: single layer of cells (0.1-0.3 micron) - site of capillaries; the drug needs to reach
this site in order for absorption to occur
Particle size of 1-5 (≤ 2 microns) microns required to reach deep lung
Aerosols depend on the power of a liquefied or compressed gas to disperse the active
ingredients in a finely dispersed mist, foam, or semisolid
The valve assembly and propellant are an integral part of the formulation
Particle size controls the site of action
·
20-60 µm: localized effects in trachea
·
< 6 µm : respiratory bronchioles
·
≤ 2 µm: alveolar ducts & alveoli
Advantages of Aerosol delivery:
1. Rapid onset, reduced dose, avoidance of first pass effects (blood from the lungs do not go
to the liver)
2. No contamination of residual product; sterility can be maintained
3. Particle size of mist controlled by formulation & valve design; dosage controlled by metering
valves
4. Container protects against moisture, oxygen, & light
5. Cool sensation for topical delivery
Aerosol propellants
·
Fluorinated hydrocarbons
o
Effective (inert, non-flammable, etc.) but harmful to the environment
o
The ones containing fluorine are not on the market anymore
·
Hydrocarbons
o
Not used very much (flammability hazard)
·
Compressed gas
o
Pressure drops with each administration; not as powerful/effective as liquefied gases,
which maintains constant pressure until liquid phase is depleted from the can
o
Not used for deep lung delivery, used more for topical
Aerosol Principles
·
Vapor pressure of propellant exerts pressure in all directions in a aerosol container
·
Upon actuation of valve, this pressure forces the liquid up the dip tube and out the valve
orifice
·
Upon release, propellant vaporizes to break the formulation into a fine mist
Aerosol Systems – Type & amount of propellant, product concentrate, and the valve all control
the pressure/type of aerosol (spray)
·
Liquefied Propellants (powerful)
·
Compressed Gas systems (not as powerful)
Aerosol Devices
·
Metered Dose Inhalers (MDIs)
o
Metering valves control the amount dispensed upon actuation
o
CFC-free MDIs available; uses hydrofluoroalkane-134a or HFA-227 as a propellant
·
Nebulizer
o
Does not use propellants
o
Air stream (either via manual or compressed air) breaks drug solution into fine particles
which can be inhaled
·
Dry Powder Inhaler (DPIs)
o
Stable dry-powder formulations can be used, especially for peptides and proteins
o
Can deliver drugs to the deep lung
o
Less risk of microbial growth
o
Unlike liquid formulations, aerosol particles contain drug in very concentrated form,
allowing delivery of therapeutic dose in one to three puffs
o
Micronized drug inhaled directly into lungs
o
e.g., a dry powder formulation in blister packed doses and a device designed to use a
sonic velocity jet of air to break up the very fine powders that tend to agglomerate due to their
very small size
Inhaled Insulin Delivery System – Exubera (Pfizer Sanofi-Aventis); withdrawn from market
Proper use of Aerosols
·
Coordination of inhalation & actuation required
·
A spacer device may be required (used to allow liquid particles to break into fine mist)
·
To ensure continuity of therapy, pharmacist can share with patient ways to assess how
much medication is left in the canister
·
Dose counters can be used to keep track of aerosol levels
·
Contents under pressure. Do not puncture or incinerate or expose to heat. Keep out of
reach of children
·
Avoid inhaling (except for inhalation aerosols)
·
Use only as directed
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326 Parenterals& Admixtures: Routes of Administration Phuong Tran
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Intravenous: can give large volumes slowly because it is diluted in the blood unless the
patient is losing fluid, then you can give it to the patient quickly.
i. Make sure to use aseptic precautions
ii. Rapid action
iii. May lead to thrombus formation (blood clots)
iv. No bacteriostatic agents
v. 100 mL to 1 L
vi. Typically used as means of fluid replacement, electrolytebalance restoration, or for total parenteral nutrition
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Intramuscular: 2-5 ml
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Intradermal: 0.1 ml (in skin)
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Subcutaneous: under skin; 1.5 ml
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Others: intra-artciular (joints), intrasynovial (synovial joint fluid), intraspinal, intrathecal
(spinal fluid), intra-arterial (arteries), intracardiac
●
Intravenous admixture: an IV fluid with one or more added sterile projects for
administration
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Free from particulates and pyrogens
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Additive must be compatible with LVP
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326 Parenterals& Admixtures: Aseptic Techniques & Facility Design
Phuong Tran
Centralized pharmacist is responsible
Errors are made due to attitude and dosage
Prepared in environmentally controlled areas by trained personnel & meets purity standards
Meet compendial limits for particulate matter
Production facilities and procedures:
Must have special floor plan; filtered air supply; uv lights; sterile equipment; and work clothing
Personnel access to all controlled areas through change rooms known as anterooms
Sources of product contamination: personnel, air, equipment, and materials
HEPA filters:
i. Laminar-airflow work benches (LAFW) are available for aseptic handling on a small scale while
clean rooms are available in an industrial setting
ii. Should meet class 100 standards and placed in buffer area (class 10000; ISO class 7) and
anteroom or support area outside of buffer area (ISO class 8; or class 100000)
Facility Design:
IV room: low traffic area; LAFW in low traffic area within the IV room
Direct and contiguous compounding areas should be cleaned and sanitized
Filtered and cooled airflow and maintain positive pressure
Ceiling and floor – non-porous, non-shedding material; curved interfaces and flush-mounted recessed
fixtures
Avoid traffic and unnecessary movements; no eating or drinking; verbal communication through
intercom or telephone
Use SOP: standard operating procedure
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326 Parenterals& Admixtures: Formulation Kelly Kiefer
1.
2.
Types of Injections for SVPs
1. Injection: Solutions ready for injection
2. For Injection: Dry soluble products with or without excipients and ready
to be combined with a solvent
3. Injectable Suspension: Suspensions ready for injection
4. For Injectable Suspension: Dry, insoluble and unstable products, ready
to be suspended in a vehicle
5. Injectable Emulsions – fine particle size, propfaol (150 nm size in the
dispersed phase) IV sedative milk of “amnesia” because it is a sedative
Intravenous Admixtures
1. IV Admixture: An IV fluid with one or more added sterile products for
administration
2. Admixtures made under laminar flow hoods using strict aseptic
techniques to maintain the sterility and freedom from particulates &
pyrogens
3.
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Additive (drug) must be compatible with the LVP
326 Parenterals& Admixtures: Containers Kelly Kiefer
1.
2.
3.
4.
5.
6.
7.
8.
Sterile Water for Injection USP: WFI sterilized & packaged in single dose
containers of NMT 1 L size
1. Distillation, reverse osmosis, multi/single dose
Single Dose containers – ampuls & LVP (100 mL or more)
1. No preservative
2. Only use one time
Multiple dose containers – multiple dose vials & SVP (<100mL)
1. Contains preservatives
2. Can use more than once
3. Coring—cutting out a piece of rubber as you go in à the rubber resealing
is comprised
Glass containers
1. IV Fluids (sizes of 250, 500, or 1000mL)
2. packaged in vacuum; vented or non-vented
3. Composed of silicon dioxide with varying amounts of other oxides
4. USP Classification:
1. Type I – borosilicate glass; inert; ampuls
2. Type II – sodium calcium; LVPs
3. Type III – sodium calcium; solids
4. NP – not used for parentals
Plastic containers
1. IV Fluids (sizes of 250, 500, or 1000mL)
2. Advantages: Un-breakable; Light (reduces transportation cost); No air
interchange required
3. Problems: May leach constituents into product or allow sorption of drug
or allow permeation of vapors; less clarity; sterilization methods limited
1. Plasticizer (leached constituents)
2. Sorption = ab (all throughout) or ad (on the surface)
4. Sorption Examples: Nitroglycerin (so use glass) and insulin on IV bags
(proteins ab/adsorb on surfaces)
Mix-O-Vial
1. Dry formulation àpress stopper and the water will mix with drug; quick
and easy for immediate use
Color-Break Ampuls
1. Marking for breakage; break away from you in the fume hood; glass
particles do end up in the solution once broken (but there is a technique
to remove the glass particles)
2. Open ampuls away from you! You do not want glass particles coming at
you!
Syringes
1. Plastic or glass – single use disposables, packaged as a sterile unit
2. Barrel & plunger; syringe tip may have locking or slip-tip connections
3.
9.
10.
11.
12.
13.
14.
Hypodermic syringes – typically, 2 to more than 60 mL; tuberculin
syringes 1 ml
Needles
1. Disposable hypodermic needles – hub and shaft; shaft tip beveled to
various angles
2. Gauge is a measure of outside diameter of the shaft; 13- to 27-gauge
3. Filter needles used in admixture compounding = in one of the steps
4. Dispose off in Sharps containers
Prefilled Syringes
1. Provide ease of use, e.g., for biotech-based drugs
2. Reduced risk of misidentification, dosage error, and contamination
3. Elimination of solution transfers can result in cost savings
4. Available in Luer and staked (glued-in) needle finishes, typically a 27G
needle for subcutaneous dosing
Administration Sets
1. Used to deliver IV fluids – sterile, pyrogen-free & disposable
2. Typical components: piercing pin, drip chamber, tubing, clamp, Y-site, inline filter
3. Y-Site: make additions, aspirate air, administer incompatible drug, avoid
additional stick
Piggyback Administration
1. Piggyback IV administration: Solutions from two containers flow into the
patient veins through a common tubing and a common injection site
2. Advantages: (1) Additional venipuncture not needed (2) Medication can
be given at intervals (3) Incompatibilities avoided (4) Some dilution (within
piggybag) possible
Infusion Devices
1. Gravity IV administration sets: many variables; may alter the accuracy of
the system
2. Infusion Pumps: these do not depend on gravity; flow rates can be
directly set, no need to count drops
Patient-controlled Analgesia (PCA)
1. Self-administration of analgesics in proportion to degree of relief desired
2.
Used to control pain postoperative pain for a variety of surgical
procedures
3. For cancer patient in chronic pain needs adjustment constantly
4. Have built in some safety
5. They will have a range of flexibility into dose

326 Biopharmaceutics: Bioavailability Lacey Moody
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Bioavailability: This term means the rate and extent to which the active ingredient or
active moiety is absorbed from a drug product and becomes available at the site of
action. For drug products that are not intended to be absorbed into the bloodstream,
bioavailability may be assessed by measurements intended to reflect the rate and extent
to which the active ingredient or active moiety becomes available at the site of action.

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Absolute: Comparing AUC of product test to AUC following IV administrated dose. You
are comparing it to something that is 100% absorbed
Relative:Comparing availability of drug to some reference. Measuring the AUC of
generic to a group of subjects compared to the brand or the drug that went through the
NDA process. If bioavailabilities are close than the drug will be approved.
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326 Biopharmaceutics: Drug Absorption Lacey Moody

Since many drugs are absorbed by simple passive diffusion, the degree of ionization can
influence absorption. Because the membrane is highly lipid in nature, the unionized form
will more easily diffuse across the membrane since the unionized form will be more lipid
soluble than the ionized form. Comparing absorption at two pH values, a weakly acid
drug molecule would be expected to be absorbed faster at the lower pH.
Important to consider the partition coefficient, which relates to the how quickly the drug
will pass through the membrane. Higher partition coefficient-->faster diffusion through
membrane
Drug must be in solution first before it can be absorbed. For optimal absorption: in
general, desirable to take medication on an empty stomach with 6-8oz of water.
Drug must cross membrane barrier, two rate limiting steps involved with absorption:
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o
Perfusion Rate Limited: it moves through the membrane easily (little resistance
from membrane). So it’s rate-limiting step is the blood flow-->Increasing blood flow rate
will increase absorption.
o
Diffusion or Permeability Rate Limited: drug slowly passes through membrane
(a lot of membrane resistance). So it’s rate limiting step is passing through
membraneàfix rate limiting step by increasing the rate at which it crosses the membrane.
If you increase the blood flow rate-->no effect on absorption

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Size of particle effects absorption: smaller particle-->generally absorbed faster and to a
greater extent, larger particle-->generally absorbed slower and to a lesser extent
Absorption from muscle or subcutaneous tissue
o
Drug only has to cross capillary wall which is very permeable (unlike the
membranes of the GI tract)
o
MW < 500 rapidly cross blood capillaries
o
Rate limited by: perfusion or blood flow rate
o
For example, if you apply heat-->blood flow is increased-->increases absorption

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Other factors that contribute to rate of absorption is the rate of gastric emptying, the
frequency of efflux carriers, area where desired drug absorption occurs (duodenum vs.
ileum)
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326 Biopharmaceutics: Bioavailability
Bioavailability – rate and extent that active drug is absorbed from a product and becomes available at the
site of action

Important to determine the amount of drug absorbed, the rate it was absorbed, the correlation of how
long the drug was in the body tissue or fluid and the patients response, and the relationship b/t the blood
levels and clinical efficacy and toxicity

Can be used to evaluate different dosage forms of the same drug or the same dosage form from
different manufacturers

When comparing bioavailability you should look at Cmax (peak height conc), Tmax (time of the peak
conc.), and the AUC

Relative bioavailability – comparing a drug product to a recognized standard

Ex : F = (AUC)a/dose a
(AUC)b/dose b

Absolute bioavailability – systemic availability of a drug after extravascular administration compared
to IV

Ex: F = (AUC)po/dose po
(AUC)iv/dose iv
326 Biopharmaceutics: Dissolution
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Dissolution – process by which a drug particle dissolves and is necessary for absorption

Differs from solubility – mass of solute that dissolves a specific mass or volume of solvent at given
temperature

Physical and chemical nature of the active drug, excipients, and method of manufacture affect drug
dissolution

Determined by Noyes-Whitney equation

dC = DA (Cs-C)
dt
h

dC/dt = rate of dissolution at time t

D = diffusion rate constant

A = surface area of particle

H = thickness of stagnant layer

Cs = concentration of drug in stagnant layer

C = concentration of drug in bulk solvent

Increase surface area of drug, increase dissolution rate (main factor that affects rate)

Adsorption of air or other substances can decrease surface area thus decrease dissolution ra

371 Pharmacy Preparedness: Regulatory Accountability Faizan Jhandiya

OSHA: Put in place in 1970
The blood borne pathogens standard:
The primary infectious organisms of concern in blood are Hepatitis B & C, and HIV.
The best technique to prevent transmission is to avoid occupational exposures to bodily
fluids.
What is the risk after exposure to: Hepatitis B- 6-30%, Hepatitis C- 1.8%, HIV- 0.3%
Treatment is very good in response to Hepatitis B. There is no good treatment or cure to
Hepatitis C. There is no cure for HIV, but some treatment options are available if
treatment is started within hours after exposure.
Needlestick Safety & Prevention Act of 2000
The most common route of exposure is through needlesticks. The least common is
through blood splashing into eyes, oral tissue, etc.
Exposure Control Plan
Identifies jobs and tasks where exposures can occur.
Describes how employer will provide training, use signs and labels, provide hepatitis B
vaccinations, ensure use of protective equipment.
Universal or Standard Precautions
Treat all human blood and body fluids as if they are infectious. In order to be effective,
this process must be used at all times in all situations.
Work Practice Controls
Wash hands after removing gloves.
No food or smoking in work areas.
Don’t attempt to bend, break, or re-cap needles.
Personal Protective Equipment
Gloves, eyewear, lab coat, resuscitation devices (dental dam)
If Exposure Occurs
Wash exposed skin with soap and water
Report exposure immediately
Irrigate eyes with saline or water
Request post-exposure medical exam
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371 Pharmacy Preparedness: Drug Information Faizan Jhandiya
Identifying Drug Information Resources
Tertiary sources—information obtained from a primary source.
Advantage--Easy to access and easy to use
Disadvantage--They might not be current and new info may be available
Examples—bound books like textbooks and reference books
Secondary sources—are compilations of info abstracted or compiled from primary
sources
Primarily accessed through a computer—online databases
Two types of databases—bibliographic and full text (full text of journals etc.)
Advantage—direct access, search more than one source at a time, tutorials (Mesh
terms)
Disadvantage—cost
Examples- IDIS, PubMed (available free of charge provided by govt.), Medline,
EMBASE, OVID
Primary sources—original or updated organizations
Advantage—more current information
Disadvantage—hard to access, hard to evaluate and interpret, lag time of publication
Examples—research studies, case reports, journals
Drug info sources are available as print, CD, online(most common), and microfiche
(least common)
Evaluating Drug Literature
Primary literature-original published or unpublished work
Evaluative studies-utilize investigation and scientific principles
Experimental studies—evaluate an intervention prospectively. (Clinical trial,
pharmaceutical research, educational assessment)
Observational studies—observe an event retrospectively (case control, cohort, follow-up,
cross sectional)
Descriptive reports-simply recount individual experiences. (Case report, pharmaceutical
practice, clinical series, program, population)
Limitations of primary lit—bias, results only applicable to similar population, retrospective
studies only show association.
Limitations of secondary lit—represent sample of entire collection of literature, negative
data not published.
Limitations of tertiary lit—only current as most recent reference, constrained by author's
interpretation, generally does not provide specific data.
Title should indicate what article is about without drawing conclusions
Author should not have preconceived notion or conflict of interest
Writing should be free of opinions or reflections of attitude.
Intro should be reflective of study, should be accurate or balanced
Methods—Design should show rational basis of comparison, address study objective,
allow support or rejection of the hypothesis.
Discussion should consider all possible relationships between events and outcomes.
Conclusion should be directly supported by info in the report. Clinical relevance should
be based on what the study shows and not what the literature shows.
Communicating Drug Information
Systematic Approach to answering a drug information inquiry
1. Obtain Demographics of Requestor (who asked the question)
2. Obtain Background information (Ask questions)
3. Determine and categorize question (Ensure you know what the question is)
4. Conduct search (when does requestor want an answer, use search strategies)
5. Evaluate, analyze, and synthesize information
6. Formulate a response (Base on considerations, notate all references used)
7. Conduct Documentation
8. Provide Response (use a professional tone and include contact information)

371 Pharmacy Preparedness: Pharmacy Calculations Tashonda LewisTaylor (you can just give conversions ie lb to kg)
Apothecary Measure Metric Equivalent
1 grain (gr) (weight) 64.8 mg (often rounded to 65 mg)
1 apothecary ounce (oz.) (weight) 31 g
1 fluid dram (volume or liquid) 5 ml
1 fluid ounce (fl. oz.) (volume or liquid) 29.6 ml (often rounded to 30 ml)
Avoirdupois Weights
1 ounce (oz) = 437.5 grains (gr) = 28.4 g
16 ounces = 1 pound (lb) = 7,000 gr
Household Measure Metric Equivalent
1 teaspoon (tsp.) 5 ml
1 tablespoon (Tbl.) 15 ml
1 fluid ounce (fl. oz.) 29.6 ml (often rounded to 30 ml)
1 pint (pt.) 473 ml (often rounded to 480 ml)
1 gallon (gal.) 3785 ml
1 pound (lb.) 454 g
1 inch (in) = 2.54 centimeters (cm)
1 kilogram (kg) = 2.2 pounds (lbs)
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371 Pharmacy Preparedness: Prescription Basics Tashonda Lewis-Taylor
•Requirements for prescription drug order:
•Full name and address of the patient
•Name and address of prescriber
•DEA number of prescriber (if a controlled substance)
•Date of issuance (the date it was written)
•Name, strength (if necessary), dosage form and quantity of prescribed drug
•Directions for use by the patient
•Refills authorized, if any
•If a written prescription, prescribing practitioner’s signature
•A serial number assigned by the pharmacy for filing

371 Pharmacy Practice: Medical Abbreviations Amber Hodge
Medical Abbreviations
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use of standard abbreviations is both effective and efficient
interprofessional communication
never make up your own
Disease States
CHD = coronary heart disease
DVT = deep vein thrombosis
HTN = hypertension
Vital signs and labs
BP = blood pressure
T = temperature
BUN = blood urea nitrogen
CBC = complex blood count
Instructions
IM = intramuscular
DNR = do not resuscitate
NPO = nothing by mouth
Procedures
CXR = chest xray
ECG = electrocardiogram
CABG = coronary artery bypass graft
Data Entry
HPI = history of present illness
PMH = past medical history
ROS = review of systems
SOAP = subjective objective assessment plan
Some abbreviations may have multiple meanings:
CC: chief complaint, critical care, creatinine clearance
ARF: acute renal failure, acute respiratory failure
RA: renal artery, rheumatoid arthritis, right arm, right atrium
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371 Pharmacy Practice: Medical Abbreviations Amber Hodge
371 Pharmacy Practice: Blood Pressure Assessment Imran Shahduddin
1. Blood pressure (BP)- an assessment of your cardiovascular health
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a.
Measurement of blood pressure is conducted at the brachial artery
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b.
Equipment used- stethoscope and sphygmomanometer
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c.
Preparation
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i.
Exam room should be quiet with a comfortable temperature
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ii. BP should not be measured if the patient has engaged in recent physical activity,
used tobacco, ingested caffeine, or eaten within 30 minutes.
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iii.
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1. Patient’s back and legs should be supported, with legs uncrossed and the feet
resting on firm surface.
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2. Arm used should be bare to the shoulder (if possible) and if garment sleeve
raised, should be loose so it doesn’t interfere with blood flow.
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3. Patient’s arm should be supported by desk/table, and arm should be level with
the heart.
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iv.
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1. Using an improperly fitted cuff results in over/under estimation of BP.
Undersized cuff results in overestimated BP.
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2. Measurement of patient’s arm circumference at midpoint of upper arm required
to select right size cuff.
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3. 22-26 cm- small adult arm; 27-34 cm- Adult arm; 35-44 cm- Large adult arm;
45-52- Adult thigh
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v. Place cuff onto bare arm approx. 2 cm above crease of elbow. Ensure midline of
bladder is directly over brachial artery (usually noted on cuff).
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vi.
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vii. Do not inflate cuff to an arbitrary level- risk of over inflation and patient
discomfort or underestimation of systolic BP. To avoid, determine pulseobliteration pressure
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1.
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2. Slowly inflation rate to approximately 10 mm Hg every 2 to 3 seconds and note
when pulse disappears.
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3. After pulse has disappeared, deflate cuff at a rate of 2 mm Hg/second, noting
when pulse reappears, which confirms obliteration pressure.
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viii. Place stethoscope (bell side) over brachial artery and inflate cuff to a level 2030 mm Hg above pulse-obliteration pressure
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ix. Next, deflate cuff at a rate of 2 mm Hg/second while listening for
the Korotkoff sounds (a series of sounds as turbulent blood flows through brachial
artery). Five different phases:
Correct position of patient
Arm measurement- common error
Cuff should fit snugly but still allow for 2 fingers to slide under.
Palpate radial pulse while rapidly inflating cuff to 80 mm Hg.
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1.
Phase 1- clear, repetitive tapping sound= systolic BP
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2.
Phase 2- audible murmurs in tapping sounds heard
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3. Phase 3 &4- muted changes in tapping sounds occur (usually within 10 mm Hg
of true diastolic pressure)
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4.
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x. To ensure diastole has been reached, continue deflating cuff for additional 10
mm Hg beyond fifth Korotkoff sound.
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xi. Obtain a minimum of 2 BP measurements at intervals of at least 1 minute and
record the average BP.
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xii.
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1.
Normal- systolic <120, diastolic < 80
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2.
Prehypertension- systolic 120-139, diastolic 80-89
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3.
Stage I hypertension- systolic 140-159, diastolic 90-99
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4.
State II hypertension- systolic >= 160, diastolic >= 100
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xiii. If patient has results that are out of the normal limits, do not tell the patient
he/she has hypertension (we aren’t qualified to do that!!!)
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1. If the BP is really high (>180/100 mm Hg), repeat the BP reading for
confirmation. If still elevated, encourage the patient to seek urgent care.
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371 Pharmacy Practice: Blood Pressure Assessment Imran Shahduddin:
same as above.
372 Pharmacy Preparedness: OSHA Monee Geary
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Phase 5- Not really a sound; indicates disappearance of sounds= diastolic BP
Blood pressure classification
Topics covered during the OSHA lecture:
OSHA and NIOSH were created as a part of the Occupational Safety and Health Act of
1970.
-Employers responsible for training their employees in the safety and health aspects
of their jobs.
OSHA-Occupational Safety and Health Administration
-Division of the United States Department of Labor
- Responsible for developing and enforcing workplace safety and health regulations
-Training should be done yearly.
-Important: All healthcare workers and people who work with CHEMICAL
HAZARDS must complete OSHA training. For example: A photo employee at
Walgreens, a nurse, or a construction worker would all have to complete OSHA
training.
NIOSH-National Institute for Occupational Safety and Health
-Part of the CDC and the Department of Health and Human Services
-Responsible for conducting research and making recommendations for the prevention of
work-related illnesses and injuries.
Universal Precautions- precautions/standards designed to prevent the transmission of bloodborne pathogens and diseases (such as HIV/AIDS and Hepatitis B and C) in healthcare settings.
-In short, these are standards in which all human blood, body fluids, and tissues of human
origin are treated as if they were infected with a blood-borne disease.
*Things that help employees reduce chance of exposure or injury to hazardous:
-Getting vaccinations and keeping up with them
-Personal Protective Equipment (PPE)-usually provided by the employer with few
exceptions like closed toed shoes.
-Proper techniques/training used by employees to reduced exposure.
Needlestick Safety and Prevention Act
-OSHA revised the Bloodborne Pathogens Standards with this act
-Requires that all employers have an Exposure Control Plan and needle stick injury log.
Also requires employers to indentify, evaluate, and implement safer medical devices.
-NEEDLESTICKS are the most common workplace injury.
-After use, all needles should be placed in a SHARPS container.
MRSA-Methicillin Resistant Staphlococcus Aureas
-Bacterium that usually infects the skin (usually results in sores and boils)
-Mode of transmission is usually direct contact (person to person). You can also get it if
the bacteria is left on an object you touch, but that is rare.
-Hard to treat because it is resistant to many antibiotics, but can be treated.
-Mostly occurs in hospitals and long terms care facilities
-Healthy people can also get it, usually called Community Associated (CA) MRSA-the
kind you get outside the hospital setting.
Tuberculosis
-Communicable disease spread through airborne transmission
-Can be treated with drugs but with a few exceptions:
-MDR-Multi Drug Resistant TB
-XDR TB: Extensively Drug Resistant TB
-Exposure rates have decreased over the years in many states throughout the U.S.
Modes of transmission of germs: Direct contact (person to person), Airborne or
respiratory, Fecal route, or Blood contact route.
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372 Pharmacy Preparedness: Substance Abuse Monee Geary
Statistics
-1 and 10 people become addicted in their professional careers and is increasing (In
pharmacy school -> 10-15%)
-7 use, 5 abuse, 1 becomes addicted
*Two drugs that stay constant throughout the years: Marijuana and Alcohol
Definitions:
1. Use: Legal mood-altering chemicals consumed by choice in safe amounts at
appropriate times and places, in ways not harmful to self or others.
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2. Abuse: Mood-altering substances still being used by choice, but in unsafe
amounts, or at inappropriate times and places, or in ways harmful to self and others.
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3. Addiction: Powerless over mood-altering substances characterized by episodes
of loss of control and/or inability to modify drinking and drugging, even after
experiencing negative consequences - - Sometimes, but not always, accompanied by physical addiction to the chemical.
Factors of addiction-family history, availability, ignorance, overtime, stress, and
artificial invincibility.
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Identification of the Impaired Pharmacy Employee: Employment Patterns, Mental
Status, Physical Health, Professional Status, Family Life, and Community
Involvement.
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4. Intervention: A structured process in which the delusional system of addiction
is confronted in a caring, objective, and non-judgmental manner so that the
individual receives help for his/her problems.
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Intervention Team: Interventionist, Supervisor. Pharmacy Peers, Board of
Pharmacy, State PRN (Pharmacy Recovery Network), State Drug Inspectors,
Family, and Friends.
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***A special state regulatory agency: The GDNA (Georgia Drug and Narcotics
Agency)***
- The regulatory and enforcement arm of the GA State Board of Pharmacy
- All GDNA Agents are required to be pharmacists as well as certified peace
officers
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GDNA conducts background checks on intern and pharmacist applicants.
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-
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5. Recovery-Abstinent sobriety with effective and productive return to family,
job and community
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6. Treatment Options:
 Inpatient
 Short stay – Detox/Medical stabilization
 Residential
 Partial hospitalization
 Halfway House
 Outpatient
 Mutual-Help Group
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372 Pharmacy Preparedness: Drug Information Amanda Conkling
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Drug Information
1)
2)
3)
Evolution
- The university of Kentucky was the first Drug information center (est. 1962)
- A DIC is a collection of DI specialists specifically trained to efficiently retrieve,
evaluate and communicate info in order to develop evidencebased recommendations and assist in patient care decisions.
Components of a comprehensive DI service
- Answering medical/ drug inquires
- Support for clinical services
- Developing criteria/ guidelines for medication use
- Pharmacy and Therapeutics committee activity
- Publications
- In service presentations
- Poison Information
- Private Sector
- Other
Responsibilities of DI specialist (see above list- services and requirements combined)
4)
Opportunities available to pharmacists in DI as a career
- More than 80% are located in hospitals or medical centers, interfacing with
pharmacy services
- ~10% are located in colleges of pharmacy
- Involved in manages care, institution, industry, medical writing and informatics
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372 Pharmacy Preparedness: Drug Information Amanda Conklingsame as
above.
372 Pharmacy Practice: Pharmacy Calculations
372 Pharmacy Practice: Pharmacy Calculations
372 Pharmacy Practice: Chart Review/ SOAP Emily Bigby
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The SOAP note. SOAP is an acronym for Subjective, Objective, Assessment, and Plan
and it is the most common comprehensive documentation of patient information in the
healthcare system. Many HPCs use and contribute to the SOAP note section of the medical
record. By category:
Subjective: includes observations (in lay terminology) from patient, family, or HPCs to
explain the reason for the encounter. This can include symptoms, medications, allergies,
medical history, and adverse effects. An example, “I’ve felt nauseous since I woke up this
morning.”
Objective: quantitative measurements gathered during the physical exam or from
laboratory data. Includes vital signs, pill counts, test results, and medication profile.
Assessment: the HCPs analysis of the subjective and objective data. This is a brief
description of the diagnosis and a label (such as “newly-diagnosed” or “worsened”) that is used
to make patient care decisions. An example, “Gastritis due to metformin therapy- resolved.”
Plan: a step-wise plan with detailed steps to achieve an appropriate outcome in medical
terminology. Provides a time frame, monitoring parameters, and necessary patient education.
For example:
Check BP daily at home and q2 weeks in clinic
If <140/90 mmHg without SE, continue current therapy with lisinopril 10 mg q day
If 140-160/90-100 mmHg, increase lisinopril to 20mg q day
If >160/100, consider adding HCTZ 12.5mg
Patient educated on limiting sodium intake and effect of sodium on hypertension
Dietary consult regarding DASH diet
Return visit in 2 weeks
372 Pharmacy Practice: Chart Review/ SOAP Emily Bigby: same as above