Pharmacology
Basic Principles
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Pharmacology is the science dealing with the effects of drugs on living organisms.
It can be divided into clinical pharmacology and pharmacotherapeutics.
o Clinical pharmacology is the study of the effects of drugs on patients.
o Pharmacotherapeutics is the use of drugs to treat patients for
diagnostic/preventative purposes, etc.
o Pharmacology differs from pharmacy, which is the preparation and
dispensing of drugs.
Pharmacology includes pharmacodynamics, pharmacokinetics, and
pharmacogenetics.
o Pharmacodynamics includes the mechanisms of drug effects, the effects of
drugs on organisms, and the movement of drugs within organisms. This
answers the question, “What does the drug do?”
o Pharmacokinetics involves the absorption, distribution, metabolism, and
excretion of drugs used by the body. This is answering the question,
“What does the body do to the drug?”
o Pharmacogenetics studies the relationship between genetic factors and
drug responses. The same drug can act differently in two different
organisms.
A drug can be defined as any substance that interacts with living organisms or any
substance used to prevent, diagnose, or treat a disease. Medicine is defined as
anything that contains at least one active medication.
o Basic drug actions can be divided into those that produce stimulation
(produce an increased effect), or depression (produce a decreased effect).
Some drugs can do both.
Patients can develop a tolerance to a drug, meaning that there is a decreased
effectiveness of a drug with repeated use. This tolerance can be even termed
tachyphylaxis, which is a rapidly-developing tolerance, even within minutes.
o This tolerance can lead to dependence, either physical or psychological.
This is a condition in which exposure to a drug would cause a used to
experience a withdrawal (abstinence) syndrome if the drug was abruptly
discontinued. With dependence, the user often “craves” the drug.
Drugs produce many effects to the used.
o An idiosyncratic effect is an unusual and unexpected response to a drug.
Therapeutic effect- the desired effect of the drug. The toxic effect is any
undesired effect of a drug. A side effect is any effect of a drug other than
the therapeutic effect when therapeutic doses are used (not overdosed).
These can be expected. Not all side effects are harmful.
Synergism is what occurs when more than one drug is taken at a time.
o Additive effects are those in which the individual effects of the two drugs
equal the combined effect of both. (Drug 1 + 2 = 3). Supra-additive effects
mean that the added effects are greater than the individual effects (Drug 3
+ 4 = 30). Antagonistic (subtractive) effects mean that the effect of the
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two drugs together is less than the individual drugs. An example of this is
when a stimulatory drug is taken with a depressant. They can cancel each
other out and have no effect.
o Potentiation is when one drug may become more potent with the addition
of another.
Toxicology is the study of effects of poisons on living organisms.
Drug Names
 The chemical name is the full name given by scientists.
 Non-proprietary (“Generic”) names are the names used for testing purposes. It
soon becomes the “official/legal” name and must appear on the bottle.
 Proprietary (“Trade”) names are the names that are on the patent. The owner
holds the sole patent for seventeen years. This is good for those that hold the
patent, because after seventeen years, the Doctors are used to writing the original
trade name on the prescriptions. Trade names are not always required or used.
Prescription Writing
 A prescription is a verbal or written order for a drug issued by a properly licensed
and authorized health care practitioner.
 Two groups of drugs exist.
o Prescription drugs (aka Legend Drugs) are prohibited by federal law from
being dispensed without a prescription. It can either be a brand name or
generic.
o Over the counter (OTC) or non-legend drugs have a higher safety profile
than legend drugs, generally ½ the Rx prescription strength. Patients can
purchase these without prescriptions.
 Requirements of the prescriber. These should be performed during the writing of
the prescription.
o Disclosure of sufficient information to make informed consent.
o Duty to disclose risk of proposed treatment
o Duty to describe alternatives to proposed therapy.
o Duty to disclose any abnormalities and to advise of diagnostic procedures
which could be undertaken to determine the significance of the findings.
o Documentation.
 Drug Utilization Evaluation (DUE) is typically performed by the pharmacist
filling the prescription. The checklist should also be followed by the prescribing
doctor.
o Appropriateness and safety of drug use
 Indications and contraindications, including risk factors
 Age and weight of patient and severity of condition
 Doses must be altered when giving to children and the
elderly (cut in half), as well as women or men of smaller
stature.
 Concurrent drug use (interactions of polypharmacia)
o Over-utilization/ Under-utilization
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Dosage, quantity dispensed, frequency of dose, interval between
prescriptions, and duration of therapy
Contents of a Prescription
o Doctors name and degree, address, telephone number, license number,
DEA number.
o Superscription
 Patient demographic information
 Date of prescription
 Rx symbol (superscription) = “take as follows”
o Inscription
 Name of drug (either generic or trade name)
 Concentration (%, mg, etc)
 Dosage formulation: ophthalmic ointment, suspension, solution,
capsule, tablet, etc.
o Subscription
 Quantity- amount of drug to be dispensed. This is designated as #
followed by number of ml, grams, pills, etc.
o Signatura- Directions for patient use
 Sig symbol (signa, label)- “Do it this way”
 Directions to the patient on how to properly use the medication, as
per doctor’s orders
 Which eye, dosage, duration of the dosage, and special
instructions to the patient
o Shake?
o Signature of the prescriber
o Refill/generic information.
 Avoid unlimited refills. Only rx enough medication to do the job.
 Instruct the pharmacist regarding any generic substitutions
allowed.
Commonly used abbreviations
o Qd- once a day
o Bid- twice a day
o Tid- three times a day
o Qid- four times a day
o Qhs- every night at nedtime
o Prn- as needed
o Q1h- once an hour
o Gtt- drops
o Ung- ointment
o Sol- solution
o Susp- suspension
o Po- by mouth.
How to write an effective prescription
o Make it legible and in black ink.
o Avoid abbreviation of drug names, otherwise use Latin abbreviations.
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o Avoid confusing decimal designations. Use zeros before and after, i.e.
1.0% or 0.25%
o Be specific with timing of dosage. Instead of tid, could say breakfast,
lunch, and dinner. Also avoid using vague phrases, such as ut dict or prn
in your instructions to the patients. This avoids over & under-utilization.
o Reasons for medication can be included on the prescription.
o Ask the patient to tell you what they heard you say.
Legal responsibilities of the prescriber
o Falls under individual state licensing boards
o Prescriptions of controlled substances by those licensed to prescribe are
under state law and should be registered with the Drug Enforcement
Administration (DEA).
 Controlled substances are drugs that act on the CNS, possessing
significant abuse potential and potential to produce psychological
and physiological dependency.
 Schedule I- High abuse potential and no accepted medical
use (i.e. heroin, marijuana, LSD).
 Schedule II- High abuse potential with severe dependence
liability (i.e. cocaine, oxycodone, percodan).
 Schedule III- Moderate abuse potential and a dependency
liability (i.e. codeine, hydrocodone, vicodin).
o Optometrists can prescribe most of these.
 Schedule IV- Lower abuse potential with limited
dependency liability (i.e. benzodiazepines, propxyphene,
darvon).
 Schedule V- Limited abuse and dependency potential (i.e.
OTC cough suppressants with codeine).
 Careful control must be taken of DEA number and Schedule II
blanks.
 Federal regulations may be superceded by stricter state regulations.
o Rules and regulations related to unlabeled use of drugs
 The FDA does not regulate the practice of health care. Off label
uses are appropriate, based on clinical studies, published peerreview literature, and consensus among prescribers (“community
standard of care”). Off label prescribing is not considered research,
does not require patient consent, and does not require prior
approval by an IRB. This does not mean that you cannot get
consent anyway.
 Good risk management requires that you get patient consent prior
to any off label use. Inform the patient that it is not “FDA
approved.”
Brand name vs. generic products
o The FDA evaluates generic products compared to innovator’s brand name
product
o Critical areas
 Contain the same active ingredients.
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Is of similar (not equal) bioequivalency or bioavailability. This
means that there can be an upward or downward variation of no
more than 20% between the two products.
Produces same pharmacologic and therapeutic effects in vivo.
Meets requirements for manufacturing, etc.
Labeled with same claims, warnings, and information as
innovator’s brand name product.
Evaluation of New Drugs
 Origins
o Folklore, extracts, etc. These were concocted by “Medicine Men.” They
usually produce a placebo effect. Pharmacognosy is the study of extracting
chemicals from plants and animals.
o Pharmaceutical chemistry is the major source of medicine today. Scientists
alter the structure of existing drugs to make them more effective.
 Animal (Preclinical) Testing
o Used to be done on humans hundreds of years ago, but now it is usually
done on mice or rodents. This is done to determine basic pharmacologic
and toxicologic information.
o This is either done in an acute (administration of one dose to get a basic
idea of the effect), subacute (administration of several doses to note extra
effects), or chronic manner (administration over a long period of time).
This is a minimum of 2 years with the FDA. After this, the medicine is
given to another species, with varied doses. The entire process takes 3-4
years.
 Approval of Investigational New Drug (IND) Permits by the FDA allow for
testing on humans.
 Human Testing
o Phase I- Healthy volunteers. This is to study what the drug does. It starts
with a small dose (according to body size) and is worked up until an effect
is achieved. The safety profile and safe dosage is thereby determined. This
phase is placebo-controlled and lasts about one year.
o Phase II- Sick volunteers. This is the moment to test the drug in
individuals that would benefit. The kinetics, efficacy, optimal dose, and
adverse effects, etc. are being studied. Safety is still monitored. This phase
is also placebo-controlled, double masked, randomized, and lasts about 23 years.
o Phase III- Many patients. These are tests in “real life” settings/uses with a
heterogenous population. It is a multicenter, double masked, placebocontrolled, long-term phase to evaluate safety, efficacy, optimal dosage,
and side effects. It lasts about 3 years.
o Approval of new drug administration (NDA) allows one to market and sell
the drug.
o Phase IV- Post-Marketing Surveillance lasts indefinitely. Practitioners fill
out forms regarding the drug, side effects, etc. At this time, all of the drugs
are listed in USP (US Pharmacopeia) and the PDR. Drugs can still be
withdrawn in this stage.
o Modifications
 Treatment IND- A drug used on compassionate-use basis in lifethreatening illnesses.
 “Fast track”- Expedited clinical testing and accelerated approval
for promising drugs.
 Parallel track- Uses experimental drugs as soon as possible in the
development process.
o 1/5,000 make it all of the way
o All studies must be blind.
Pharmacodynamics
Drug Receptors
 Drug receptors are macromolecules or portions of a molecule with which a drug
binds and reacts to bring about a response. Receptors are usually portions of
membrane-imbedded polypeptide molecules (proteins). These are amino acids
with a constant order, but varied location. Effectors are molecules that translate
the drug-receptor interaction into a change in cellular activity.
 Definitions
o Agonist- this is a drug capable of fully activating the effector system when
it binds to the receptor. A partial agonist produces less than the full effect,
even when it has saturated the receptors.
o Competitive antagonists- these are drugs that bind to the receptor in a
reversible way without activating the effector system for that receptor.
Increasing drug dosage increases effects. However, the effects of
irreversible antagonists cannot be overcome by adding more agonist.
o A physiologic antagonist is a drug that binds to some other receptor,
producing an effet opposite to the produced by the drug it is antagonizing.
o Efficacy refers to the intensity of the effect that a drug can produce,
regardless of dose. Thus, maximal efficacy is the greatest degree of effect
an agonist can produce. It depends on the number of drug-receptor
complexes formed.
o Potency is an indicator of the amount of the drug needed to produce a
given intensity of effect. A small dose of a more potent drug will bring
about the same intensity of response as a large dose of a less-potent drug.
In graded dose-response measurements, the effect usually chosen is 50%
of the maximum effect (EC50). Potency is determined mainly by the
affinity of the receptor for the drug.
 Drug-Receptor Interaction
o The formation of the drug-receptor complex leads to a biological response.
The magnitude of the drug effect depends on its concentration at the
receptor site, which in turn is determined by the dose of the drug
administered.
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o Drug binds to the receptor
 The receptor recognizes the drug molecule. Different kinds of
receptors recognize different drug molecules. They are very
specific. Some drugs bind to one kind of receptor, while other
drugs bind to more than one kind of receptor. Some kinds of
receptors bind to one drug, while other kinds bind to more than one
drug.
 Binding forces may be covalent bonds (rare), ionic bonds
(reversible, common), hydrogen bonds (common), hydrophobic
bonds, or Van der Waals attraction
 Kinds of Drug-Receptor Interactions
 Direct agonism- direct stimulation/activation via direct
bonding
 Allosteric agonism- attachment to another site changes
conformation to produce stimulation
 Direct antagonism- direct deactivation/inhibition
 Allosteric antagonism- indirect deactivation
 Intracellular antagonism- the theoretical cascade inside a
cell that makes the receptor less sensitive.
 Equilibrium Binding Constant
 L + R ↔ [LR]
o This means that the reaction goes either way,
because there is no covalent binding
o L = Ligand (Drug). R = Receptor
o LR = Complex. This brings about the action of the
drug.
 k1[L][R] = k-1[LR]
o Decrease L or R to decrease LR activity.
o k1 = association rate constant
o k-1 = dissociation constant
 [L][R]/[LR] = k-1/k1 = Kd
o Kd= Equilibrium Association Binding Constant
Drug-Receptor Signalling Mechanisms
o Once an agonist drug has bound to its receptor, some effector mechanism
is activated. For many useful drugs, the effector mechanism is located
inside the cell or modifies some intracellular processes.
 More lipid-soluble agents (e.g., steroid hormones) may cross the
membrane and combine with an intracellular receptor.
 Ion channel-regulating drugs (e.g., acetylcholine at the nicotinic
receptor) may directly regulate the opening of an ion channel.
 Enzyme-regulating drugs (e.g., insulin) may combine with the
extracellular portion of the membrane-spanning enzymes and
modify their intracellular activity.
 Drugs may bind to receptors that are linked by coupling proteins
(called second messengers) to intracellular effectors. The best
defined examples are the sympathomimetic drugs, which activate
or inhibit adenylyl cyclase by activating “G” proteins that have
either stimulant or inhibitory effects on the cyclase.
o Direct control of ion channels
 Nicotinic acetylcholine receptors
 Found on motor end plates, in autonomic ganglia and in the
CNS. They are ligand-gated, where the ligand is
nicotine/acetylcholine. The channel opens when two
acetylcholine molecules bind to the two alpha subunits,
causing activity.
 Sodium-channel receptors
 This is a type of voltage gated receptor that is opened by
membrane depolarization. It is found in skeletal and cardiac
muscle.
 GABAA receptors (and GABAB)
 GABA (inhibitory) is released from neuronal endings. It is
also associated with chloride channels, which as also
inhibitory. These receptors are ligand gated.
o Generation of a second messenger
 May involve G proteins (guanosine nucleotide regulatory proteins)
 These consist of alpha, beta, and gamma subunits.
 In the inactive state, GDP is bound to the alpha subunit of
the protein. Receptor activation (by the ligand) causes
release of GDP, binding of GTP, and a separation of the
alpha subunit form the beta and gamma subunits. When the
GTP is bound to the alpha subunit of the protein, it is now
said to be in the active state.
 The GTP-bound protein then reacts with adenylate cyclase
to convert ATP to cAMP (cAMP is the second messenger).
cAMP activates (phosphorylates) cAMP-dependent protein
kinase, leading to various cascades.
 The G protein then hydrolyzes GTP to GDP, whereupon
the alpha subunit recombines with the beta and gama
subunits (therefore once inactive)
 Gs proteins (stimulatory) bring about synthesis of cAMP
and Gi (inhibitory) proteins inhibit synthesis of cAMP.
 May involve phospholipase C
 The ligand-bound receptor activates the alpha subunit of a
Gq-protein. The alpha subunit reacts with phospholipase C,
increasing its activity. Phospholipase C catalyzes
hydrolysis of membrane phosphatidylinositol 4,5biphosphate (PIP2). Hydrolysis releases inositol 1,4,5triphosphate (IP3) and 1,2-diacylglycerol (DAG), both of
which are second messengers. IP3 binds to receptors in the
sarcoplasmic reticulum and causes release of calcium. This
activates (phosphorylates) several protein kinases. DAG
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activates protein kinase C, resulting in phosphorylation of
proteins in the cell membrane.
 Tyrosine-specific protein kinase receptors
 These receptors traverse the cell membrane once and
appear in pairs. They are protein kinases that are regulated
by hormones and phosphorylate proteins on tyrosine
hydroxyl residues
 The extracellular portion is the amino end of the protein. It
usually includes cysteine-rich domains. The structure is
quite variable from one receptor type to another.
 The intracellular portion contains the carboxyl end of
protein. It contains tyrosine-kinase domains and the
structure is quite constant.
 Autophosphorylation increases tyrosine kinase activity
Regulation of receptor concentration
o Up-regulation is indicated by increased synthesis of receptors (ex. Drugs
releasing plasma cholesterol increase receptors to control this) while
down-regulation is the increased endocytosis of receptors. Tolerance can
be developed due to decreased number of receptors to a drug.
Dose-Response Relationships
 Dose-Response Curves
o Graded- Dose on a linear scale, comparing drugs A and B.
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This plots the intensity (response) of the drug vs. the log of the
dose.
In this example, Drug A is more potent, because less of Drug A is
required to show an effect. The higher, the more potent.
This scale is not as practical, because a long scale is needed to
determine the effectiveness of Drug B.
Dose on a logarithmic scale, comparing drugs A and B
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These are sigmoid curves, so they are easier to compare. They are
only parallel if the two drugs have the same mechanism that is
doing the same thing. This is not always true.
 Here, Drug A is 500 times more potent, but both are equally
effective.
 The potency is the inverse of the dose required to produce a
particular degree of effects. Usually the drug performs better at
decreased dosages. The efficacy is the ability to reach and
stimulate the receptors.
 In the presence of a competitive antagonist, the log dose ersus
response curve is shifted to higher doses but still reaches the same
maximum effect. In contrast, an irreversible antagonist causes a
downward shift of the maximum, with no shift of the curve on the
dose axis unless spare receptors are present.
o Dose on a logarithmic scale: effects of antagonists.
o Quantal
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This is the percentage of animals responding to a particular extent
as a function of the dose.
 It does not measure intensity. When the dose required to produce a
specified intensity of response is determined in groups within a
population, the quantal dose-response relationship is defined.
When plotted as the percentage of the population expected to
respond at each dose level versus the log of the dose administered,
a cumulative quantal dose-response curve, which is usually
sigmoidal, is obtained.
 The median effective (ED50), median toxic (TD50), and medial
lethal (LD50) doses are extracted from the experiments carried out
in this manner.
Statistics Useful in Measuring the Safety of a Drug
o The Median Effective Dose (ED50) is the dose which is expected to elicit
the specific response in 50% of the organisms tested.
o The Median Lethal Dose (LD50) is the dose which is expected to be lethal
to 50% of the organisms tested.
o Therapeutic Index = LD50/ED50.
 This is an estimate of the safety of a drug, since a very safe drug
might be expected to have a very large toxic dose and a small
effective dose.
 This statistic is required to be known in a few species by various
routes of administration before it is tested in humans. The numbers
vary with the route of administration. A therapeutic index of at
least 20 is required to test the drug in humans. The smaller the
number, the greater the risk. An increased therapeutic index means
that the two curves are further apart. Two drugs can have the same
therapeutic index but different degrees of safety
o Clinical margin of safety: LD1/ED99
Pharmacodynamics
 This is the mathematical relation of the movement of drugs.
 Biological Half-life- Length of time required for half of the drug to disappear
from the body.
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o Mt = M o / 2 n
 Mt = amount of drug present at time t
 Mo = amount of drug present at time 0
 n = number of half-lives since time 0
Rate Constant of Absorption/Metabolism/Elimination- The concentration
decrease per unit time per unit of concentration. This is the instantaneous rate of
elimination.
o ke = ln2 x 1 / t1/2 = 0.7 / t1/2
 ke = constant of elimination
 t1/2 = biological half-life of the drug
 Ex: If t1/2 = 7hr, ke = 0.1 hr-1 or 10%/hour
Effect of Doubling the Dose of a Drug- Every time a dose of a drug is double, one
half-life is added to the duration of the drug. The half-life does not double.
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Repeated Dosing
o The plateau is the average amount of the drug in the body.
o Dose of drug needed to maintain plateau
 Plateau amount of drug present in the body
 APA = 1.44 x D x t1/2 / T
o APA = Average plateau amount
o D = dose
o t1/2 = biological half-life of the drug
o T = dosing interval
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Ex
o t1/2 = 4hr, T = 8hr, D = 10mg
 APA = 1.44 x 10 x (4/8)
 = 7.5mg of drug in body
A total amount is needed to be effective. This formula is
used to decide the dosing interval, as well as the average
amount present in the body.
Also,
o APA = Ra / ke
 Ra = rate of administration
 ke = elimination constant
o Css = APA / Vd = Ra / keVd
 Css = concentration of the drug at the steady
state
 Vd = apparent volume of distribution
 = Dose / Concentration (D/C)
 Ra = rate of administration
Loading Dose
o Dl = Css x Vd
 Dl = loading dose (typically 2x the dose prescribed)
 Dl = APA, so if the patient is required to have 100mg in the body,
100mg should be prescribed.
Pharmacokinetics
Absorption of Drugs
 Absorption is the transfer of a drug from its site of administration to the blood
stream. The rate and efficiency of absorption depend on the route of
administration.
 Absorption Mechanisms
o Passive transport means that no metabolic energy required. The
concentration gradient is the driving force. The drug moves from regions
of high to low concentrations.
 Diffusion
 Membranes are lipophilic, so highly lipid-soluble drugs
cross readily, while highly water-soluble do not. Ionization
makes a drug molecule less lipid-soluble and more water
soluble. Drugs that are weak acids are non-ionized,
therefore absorbed.
o pKa = pH + log [HA] / [A-]
 pKa = -log of the dissociation constant. This
is the point in which ½ is ionized and ½ is
not.
 pH = -log of the hydrogen ion concentration
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[A-] = concentration of the ionized form of
the drug
 [HA] = concentration of the nonionized
form of the drug
 If pH = pKa, this means that there are equal
amounts of ionized and nonionized
molecules.
o Ka = [H+][A-] / [HA]
o HA ↔ H+ + A Many drugs do this.
 Drugs that are weak bases are the opposite of acids.
o pKa = pH + log [BH+] / [B]
 Acidic drugs tend to move toward an area of higher pH
where they get trapped, called Ion Trapping. Basic alkaline
drugs tend to move towards an area of lower pH.
 Facilitated diffusion needs a carrier molecule, i.e., amino acids, to
transport molecules in/out, until there is a same concentration on
both sides of the membrane. This is like active transport, but does
not move against a gradient.
 Filtration means that the particles move with something, such as
water. It is the same as simple diffusion, except the membrane
pores involved allow for selection of certain molecule sizes, e.g.
glomerular membrane of the kidney. This is seen mostly in the
kidneys.
 Endocytosis (Pinocytosis) is when the cell forms a vacuole to
“drink up” the drug. This is seen with large particles (MW>900),
such as proteins.
o Active Transport requires ATP and works against a concentration
gradient.
Routes of Administration
o First pass- through the liver
 Duodenum  portal vein  liver (where most drug metabolism
occurs)  hepatic vein  heart  circulation
o Enteral (Gastrointestinal Tract)
 Oral (Mouth  Stomach)- 1st pass
 Some drugs are absorbed better in one area than in another.
No absorption occurs in the mouth, because the food does
not stay there for long. There is a large absorptive area in
small intestine (duodenum), while there is little absorption
in stomach (ethanol). The gut has microvillus to increase
absorptive surfaces.
 Few specialized transport mechanisms are seen here. It is
possible that there is only passive diffusion. This exists
especially for amino acids
 Factors that can affect absorption
o Secretions- Bile changes the pH, without changing
the pKa. Another example is pepsin in the stomach
destroying proteins.
o Other xenobiotics (foreign compounds, i.e. mineral
oil dissolves lipids, etc)
o Changes in GI motility- Increased peristalsis means
decreased absorption
o Concentration- Increased concentration means
increased absorption
o Physical properties of the preparation (solutions,
suspensions, and liquid are all absorbed, but solids
are the most absorbed).
 Sublingual- Avoids first-pass metabolism
 If placed under the tongue, the contents go to the venous
system to the heart via sublingual veins. Few drugs are
given this way (nitroglycerin, etc).
 Buccal- Avoids first-pass metabolism
 In cheek- similar mechanism to sublingual
 Rectal
 Drugs placed here go to the liver via first pass metabolism.
This is used in unconscious patients or for drugs that cannot
be given through IV.
o Parental- Avoids first pass
 Subcutaneous
 Injected under the skin, going directly into the circulation.
 Absorption increases with increased temperature and
massaging.
 Intramuscular
 Injected into the muscle
 Intravenous (IV)
 Injected into the vessels
 The produces the fastest, yet most dangerous, response,
because there is no going back
 Intra-arterial
 Just as fast as IV. This is not administered a lot. Used
mainly with tumors where the drug is injected upstream so
that the tumor gets the majority of the drug.
 Intrathecal
 Injected into CSF (antibiotics, anesthetics, etc)
 Bypasses the blood brain barrier.
 Intraperitoneal
 Injected into peritoneal cavity (belly) (ex. rabies medication
and dialysis).
o Pulmonary
 Physical form of drug- Gas (anesthetics, i.e. NO2), Vapor (liquids
heated to form a gas) and Aerosol (suspended in air).
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The size of the drugs needs to be ~1 micron to go to the alveoli. If
<0.1 micron, it is breathed out again.
The rate of absorption is proportional to the concentration
difference of alveoli and plasma. 0 = complete absorption. It also
depends on the blood/air solubility coefficient. If high, the drug
goes into blood and vice versa.
Removal of particles (Pollutants, solids, etc.) is performed via
ciliary transport (elevator) and alveolar macrophages that carry
junk away to lymphatics (~0.5mm/min).
 Smoking coats cilia, therefore particles go to alveoli,
leading to cancer.
o Dermal
 Most absorption is through the epidermis. None is through the hair
follicles or sweat glands. Therefore, it is better to apply to hairless
areas. Specifically, diffusion is through the stratum corneum.
Permeability can be increased by wetting the skin, to increase
permeability, wash off oils with soap.
 Some diffusion occurs through the dermis easily (i.e. nicotine).
o Non-GI tract mucous membrane (i.e. nasal)
o Placental
 Unintentional. Mom passes increased concentration to the baby.
o Ocular- Usually causes only a local effect
Distribution of Drugs in the Body
 This is the process by which a drug leaves the blood stream and enters the
extracellular fluid or the cells of the tissues. The delivery of a drug primarily
depends on blood flow, capillary permeability, and the degree of binding of the
drug to the plasma and tissue proteins.
 The most important factors affecting distribution
o Size of the target organ
o Protein binding- drug may bind to inert binding sites and wont be used on
receptors
o Blood flow
o Membrane permeation
o Tissue solubility
 Physiologic compartments
o Tissue Reservoirs
 These are binding/storage sites and contain bound/stored drugs.
 Proteins
 These are wide-spread. A common example is plasma
albumin in the blood. While bound to protein, the drug is
inactive.
 More binding indicates increased concentration.
Concentration says nothing about effect.
 Free drugs are usually seen in equilibrium
 Hepatic and renal tissue



Lipid Tissue, if lipid soluble (ex. anesthetic ether- the patient
awakens slowly due to the drugs in the reservoir).
 Bone- Stores tetracycline and lead
o Receptors
o Blood Brain Barrier
 This is the endothelial lining of vasculature in CNS that blocks the
crossing of some drugs into the CNS. It is hard to cross, except for
anesthetics.
o Transplacental passage
 The placenta is a partial barrier to some drugs, but most drugs will
be found in the same concentration in the fetus as in the mother
within an hour. In many cases, the concentration in the fetus will
be greater because of the inability of the fetus to metabolize drugs
as well as the mother.
 Increased concentration occurs in the fetus, because it cannot break
down the drug.
Redistribution
o Some drugs are distributed twice in the body.
o Seen with thiopental (pentothal, an anesthetic). It goes from the Blood 
brain  muscle  fat. Each compartment is short-acting.
Apparent Volume of Distribution
o A formula is used to find out how much of a drug is distributed to various
known areas os the body. This is apparent, not real.
o Vd = D/C
 D = dose of drug
 C = concentration of drug in plasma
o Plasma only: 4L
o Extracellular fluid: 14L
 14L can be plasma and pancreas. (This is why it is only apparent).
o Total body of water: 42L
o Binding >42L (The drug is being stored).
Metabolism of Drugs
 This is how the drug is eliminated by biotransformation and/or excretion. The
actions of many drugs are terminated before they are excreted because they are
metabolized to biologically inactive derivatives. Some drugs, i.e., pro-drugs, are
inactive when administered and must be metabolized in the body to become
active.
 The liver is the major site for drug metabolism, but some drugs may biotransform
in other tissues. Termination of the drug effect occurs through mechanisms in the
liver, as well as the lungs, skin, and kidneys.
 No energy changes with this.
 Metabolism occurs to get rid of the drug from the body, rid the body of
unrecognizable foreign chemicals, and to make drugs water soluble so that they
are excreted and not filtered/reabsorbed (and less active).
 Factors affecting metabolic rates

o Age- Very young and very old patients have less metabolism, so give
them a lower dosage (½ - ⅓).
o Exposure to other chemicals
 Medications- Such as those that include cytochromic activity
(P450) (ex. Phenobarbital for epilepsy metabolizes faster, therefore
needs increased dosage, etc.).
 Diet- Chronic alcoholism increases metabolism (acutely
decreases). Grapefruit juice decreases metabolism, therefore drink
it with medications.
 Environment- i.e. Occupations (those that ruin the liver, etc)
o Presence of disease- Fevers increase metabolism and frostbite decreases it.
Metabolic Pathways
o Some drugs only go through phase I, others only phase II. Some neither.
Usually it goes through I then II. This is studied via metabolites.
o Phase I transformation includes small steps to polarize molecules. This is
considered a “preparation for phase II.” The parent drug converts to a
more polar metabolite (water soluble) by introducing/unmasking a
functional group, such as OH, SH, or NH2.
 Hydrolysis
 Oxidation
 Alkyl hydrocarbon chain oxidation
o Occurs in microsomes. The O usually goes on the C
next to the end.
 Ring hydroxylation
 Oxidative deamination
o Amine removed and replaced with an O
 N-dealkylation
o Removes an ethyl group
 O-dealkylation
 S-dealkylation
 Reduction
 Nitro group reduction  amine
 Ketones and aldehydes  alcohol
 Azo group reduction  2 amines
o Phase II transformation- larger groups. Increase water solubility or
decrease lipid solubility by conjugation of the drug molecule with a polar
moiety.
 Glucouronidation
 Occurs in 90% drugs (v. common)
 Acetylation
 Acetyl group added
 Sulfation
 Mercaptic acid formation
 Alkylation
Excretion of Drugs








Kidneys- Where the majority of excretion occurs
o Mechanisms
 Filtration occurs in the glomerulus (some in the proximal tube and
loop of Henle). This is the mechanism for lipid soluble material.
Everything except large particles are filtered. Passive.
 Tubular secretion is actcive and occurs at the proximal convoluted
tubule. Weak acids are removed this way.
 Reabsorption occurs in the proximal tubule. Highly lipid soluble
material is reabsorbed, because it easily crosses the membranes. If
polar, it remains in the tubule. Some occurs in the loop of henle.
Passive.
 Active Secretion (i.e. with penicillin) occurs in the distal tubule
and collecting ducts.
Liver
o Drugs secreted into the bile can enter the Enterohepatic circulation: Liver
 bile duct  intestine  liver again
o This form has a long t1/2, and is therefore rare.
Lungs
o Excretion of gases and volatile liquids
GI Tract
o Passive diffusion of drugs from the blood to the lumen.
o Unabsorbed drugs. Whatever is taken by the mouth that is not absorbed is
excreted.
Milk: mom  baby
“Others,” including sweat, saliva, milk, hair, and nails.
Rates of drug elimination
o First order
 Majority (90%) of drugs
 Rate changes with concentration
 Increased concentration = increased elimination
 Ct = Coe-kt
 Ct = concentration at time t
 Co = concentration at time 0
 e = base of natural logarithms
 k = constant of elimination
 t = time
o Zero order
 At = Aokt
 At = amount present at time t
 Ao = amount present at time 0
 k = rate (constant)
 Ex: EtOH 10mL/hr until about 0.08 mg/dL (state limit)
Influencing Factors

o Age: the very young or old metabolize drugs slowly. The young because
of the lack of enzymes, the old because of the slower system. Therefore,
doses must be reduced accordingly.
o Gender: significant only for some hormonal drugs, i.e., androgens and
estrogens.
o Pathology: e.g., liver disease may prlong the half-life of certain drugs,
such as diazepam.
o Genetics: some drugs can ccause significant toxic effects in individuals
with hereditary deficiencies of some enzymes.
o Diet: the only factopr that can affect metabolic rate is ethyl alcohol which
acts a lot like Phenobarbital and phenytoin on the liver. Long term use of
ETOH will destroy the liver and will decrease metabolic rate.
Quantatative Aspects
o Renal Clearance- Volume of plasma “cleared” per minute
 Depends on renal function (decreased with disease)
 RC = (Conc urine)(Volume urine secreted per hour) / Conc plasma
o Half-life: t1/2 = 0.693 Vd/ CL
o Concentration after a certain number of half-lives: C = Co / 2n
o Maintenance of dosage
 Dosing Rate = clearance x desired plasma concentration (in
average dose per unit time)
 Plateau concentration is the amount of drug that is needed to be
constantly replacing or intermittently replacing because this is the
amount that the body metabolizes or excretes.
 = (1.44)(Dose given per half life)(t1/2) / Dosing interval
 Loading dose = volume of distribution desired plasma
concentration
Drugs and Pregnancy
 General Information
o Almost every drug administered to a pregnant woman crosses the placenta
and enters the fetal circulation. Just because a drug crosses the placenta
does not necessarily mean that it is necessarily harmful to the fetus.
o The stage of development seems clearly related to exaggerated risk during
pregnancy, particularly the 1st and 3rd trimesters during which all drugs
should be given with extreme caution.
o First Trimester
 This is the most sensitive period for drug-induced fetal
malformation, because this is the period in which fetal organs are
differentiating. All major organs of the fetus are present by the end
of the first month of human organogenesis.
 During this time, all drugs, except those labeled as Category A or
B should be withheld, unless doing so would jeopardize the health
of the mother upon whom the human fetus depends for life. Even
self-prescribed OTC products should be avoided during pregnancy,
including aspirin (Category D).



o Third Trimester
 The effects of drugs in the fetus are also of special concern during
this stage because the amount of drug needed by the mother at her
weight is placentally carried to the fetus at its weight, resulting in a
drug overdose.
 The detoxifying systems of a newborn child are not fully
developed, and as a result, drugs taken by the mother during birth
may take a long time to metabolize and induce prolonged toxic
reactions. It can take up to one month for newborns to eliminate
anesthesia given to them during medicated childbirth.
 There are circumstances when pregnant women must continue to
take certain drugs to protect their children, i.e. women with seizure
disorders, bacterial infections, etc. In these cases, the potential risk
to the fetus is outweighed by the benefit to mother and her child.
Drug Testing
o Because it would be unethical to do drug testing on healthy preborn
children, fetal testing has traditionally been done on non-human species.
Because different species react to drugs in different ways, laboratory
animal studies do not rule out possible teratogenic effects in humans. As a
result, preclinical laboratory animal drug studies attempt to point out gross
teratogenicity. They do not clearly establish safety.
Pregnancy Risk Categories
o This is the drug’s relative risk to the unborn fetus. Although drugs are best
avoided during pregnancy, this rating system permits assessment of the
risk-benefit ration should drug administration to a pregnant woman
become necessary.
o Category A- Safe. Adequate studies in pregnant woman have failed to
show a risk to the fetus.
o Category B- Animal studies have not shown a risk to the fetus, but
controlled studies have not been conducted in pregnant women –oranimal studies have shown an adverse effect on the fetus, but adequate
studies in pregnant women have not shown a risk to the fetus.
o Category C- Animal studies have shown an adverse effect on the fetus but
adequate studies have not been conducted in humans. Use during
pregnancy only if potential benefits outweigh risks to the fetus.
o Category D- The drug may cause risk to the human fetus but the potential
benefits of use in pregnant women may be acceptable despite the risks,
e.g. in a life-threatening situation or serious disease for which safer drugs
cannot be used or are ineffective.
o Category X- Studies in animal studies or humans show fetal abnormalities,
or adverse reaction reports indicate evidence of fetal risk. The risks
involved clearly outweigh potential benefits.
o Category NR- Not rated
Drug Therapy During Pregnancy
o Before a drug is prescribed for a woman of childbearing age, she should
be asked the date of her last menstrual period and whether she may be

pregnant. If a drug is a known teratogen, some manufacturers may
recommend special precautions to ensure that the drug not be given to a
female of childbearing age until pregnancy is ruled out and that
contraceptives are used throughout the course of therapy. This is
especially important during the first and third trimesters. A pregnant
woman should avoid all drugs, except those essential to maintain
pregnancy. Topical drugs are not exempt from the warning against
indiscriminate use during pregnancy. Many topically applied drugs can be
absorbed in large enough amounts to be harmful to the fetus.
o Consult with and obtain permission from a pregnant woman’s PCP before
prescribing a drug. When a pregnant patient needs a drug, the consultation,
permission, and prescription should reflect the safest possible drug in the
lowest possible dose to minimize any harmful effect on the fetus.
Drugs and Lactation
o Most drugs that a breast-feeding mother takes appear in the breast milk,
therefore, the mother should be advised to breast-feed before taking
medication, not after.
o Be sure to consult with and obtain permission from a lactating patient’s
PCP in order to prescribe the safest drug in the lowest dose to minimize
any harmful effect on the infant. With a few exceptions, a mother who
wishes to breast-feed may continue to do so while taking oral medications.
Tetracyclines are an exception and breast-feeding should be temporarily
interrupted and replaced with bottle-feeding.
Drugs and Children
 Doses
o Convert the child’s weight in pounds to kilograms (2.2lbs/kg) and using
drug inserts and references, calculate the total daily dosage and administer
in divided doses as indicated by the drug manufacturer.
 Infants
o Administer the drug in liquid form, if possible. For accuracy, measure and
give the preparation by oral syringe. Never use a vial or cup. Lift the
patient’s head to prevent aspiration of the drug. Press down on the
patient’s chin to prevent choking. The practitioner may decide also to
place the drug in a nipple and allow the infant to suck the contents.
 Toddlers
o Explain how the drug is going to be prescribed, and if possible, have the
parents enlist the child’s cooperation.
o Do not mix the drug with food or call it “candy,” even if it has a pleasant
taste. Kids are not easily fooled. Let the child drink the liquid from a
calibrated medication cup rather than from a spoon. It is easier and more
accurate. If the preparation is available only in tablet form, crush it and
mix it with a compatible syrup after checking with the pharmacist to verify
that the tablet can be brushed without compromising its effectiveness.
 Older Children
o If the patient can swallow a tablet or capsule, have the patient place the
drug on the back of the tongue and swallow it with water or fruit juice.
Milk or milk products may interfere with drug absorption.
Drugs and the Elderly Population
 When administering drug therapy in elderly patients, the physiologic and
pharmacokinetic changes that may alter appropriate drug dosage or cause
common adverse reaction or compliance problems must be understood.
 As a person ages, gradual physiologic changes occur and may alter the therapeutic
and toxic effects of drugs.
o Body composition
 Proportions of fat, lean tissue, and water in the body change with
age. Total body mass and lean body mass tend to decrease. The
proportion of body fat tends to increase. These changes in the body
composition affect the relationship between a drug’s concentration
and distribution in the body.
o Gastrointestinal Function
 In elderly patients, decreases in gastric acid secretion and
gastrointestinal motility slow the emptying of the stomach contents
and the movement of intestinal contents through the entire
gastrointestinal tract. Elderly patients also may have more
difficulty absorbing drugs. These are significant problems with
drugs that have a narrow therapeutic range, in which any change in
absorption can be critical.
o Hepatic Function
 The liver’s ability to metabolize certain drugs decreases with age.
This decrease is caused by diminished blood flow to the liver,
which results from the age-related decrease in cardiac output, and
from the diminished activity of certain liver enzymes. This causes
a longer effect of the drug. Decreased hepatic function may cause
more intense drug effects owing to higher blood levels, longerlasting drug effects owing to prolonged blood levels, and a greater
incidence of drug toxicity.
o Renal Function
 Although an elderly person’s renal function is usually sufficient to
eliminate excess body fluid and waste, the ability to eliminate
some drugs may be reduced by 50% or more. Drugs excreted
primarily through the kidney must have a reduced dosage that
accommodates decreased renal function. The elderly patient’s PCP
can use laboratory tests to modify drug dosages so that the patient
receives the expected therapeutic benefits without the risk of
toxicity.
 Observe elderly patients for signs or symptoms of toxicity. If seen,
refer the patient back to their PCP. Also refer back if upon
discontinuing all medications, the patient has been cured of all
problems caused by medical treatment.


Fatalities occur due to iatrogenic causes. Hospital deaths actually
decrease at times when doctors go out on strike.
Physiologic decline is likely to be exacerbated by a disease or chronic disorder.
Together, these factors can significantly increase the risk of adverse reactions,
drug toxicity, and noncompliance.
o Adverse reactions
 Compared with younger patients, elderly patients experience twice
as many adverse drug reactions relating to drug consumption, poor
compliance, and physiologic changes.
 Signs and symptoms of adverse drug reactions include cardiac
arrhythmias, lowered pulse rates, lowered blood pressures,
confusion, weakness, and lethargy. These are often mistakenly
attributed to senility or disease. If the adverse reaction is not
identified, the patient may continue to receive the drug.
Furthermore, the patient may receive unnecessary additional drugs
to treat complications caused by the original drug. This regimen
can sometimes result in a pattern of inappropriate excessive drug
use for which the remedy is a careful cessation of drugs initiated
by the elderly patient’s PCP.
 Although any drug can cause adverse reactions, most of the serious
reactions in the elderly are caused by relatively few drugs. Take a
careful and thorough drug history and be particularly alert for
toxicities resulting from diuretics, antihypertensives, digoxin,
corticosteroids, sleeping aids, and OTC drugs.
o Noncompliance
 Poor compliance can be a problem with patients of any age and a
significant number of hospitalizations result from noncompliance
to medical regimen. In the elderly patients, specific factors linked
to aging, such as decreased VAs, hearing loss, forgetfulness,
multiple drug therapy (polypharmacy), and various socioeconomic
factors can be combined to make compliance a special problem.
About 1/3 of the elderly patients fail to comply with their
prescribed drug therapy.
 One is not always able to predict the effects of compliance or
noncompliance. It depends on a specific individual elderly patient.
They may fail to take the prescribed doses or to follow the correct
schedule. They may also take drugs prescribed for previous
disorders, discontinue drugs prematurely, or indiscriminately use
drugs that are to be taken as needed. Elderly patients may also
have multiple prescriptions for the same drug and therefore
inadvertently take an overdose.
o Patient Education
 Review the elderly patient’s drug regimen with the patient and/or
the patient’s caregivers. Make sure that they understand the dose
amount, the time, and frequency of doses, and why they are taking
the drug. Explain how they should take each oral medication that is
prescribed, i.e. with food or water, and when. Give the patient
whatever help is available to avoid drug therapy problems. Suggest
drug calendars, pill sorters, or other aids to help the elderly patient
comply, and make sure they can reach you at any time for further
information.
Drugs in Pregnancy and Breast Feeding
 All drugs are contraindicated in pregnancy. This also applies to OTC agents,
alcohol, street drugs, insecticides and other environmental pollutants. Alcohol,
when taken in excess is known to cause fetal alcohol syndrome. Most drugs taken
by a pregnant woman pass the placental barrier and may affect the embryo, fetus,
and neonate. The embryo appears to be particularly sensitive to the effect of drugs
during the first trimester of pregnancy. When organogenesis is taking place.
Drugs that do not pass the placental barrier usually consist of large molecules,
e.g., heparin. Insulin, for example, is known to be teratogenic when administered
directly to the fetus, but it does not cross the placental barrier, and hence is not
teratogenic. Excess insulin may, however, cause the fetus to develop
hypoglycemia, which may be harmful. Insulin passes into breast milk, but is
destroyed in the GI tract of the nursing infant and is harmless.
 Some drugs are excreted through the milk of the nursing mother. Unless
demonstrated otherwise, it must be assumed that any drug ingested by the mother
will be passed along to the nursing child through the mother’s milk.
 Anti-inflammatory analgesics may cause a variety of sometimes serious
difficulties if ingested in large enough dosage during critical periods of early
gestation. Some data show a strong correlation between consumption of large
doses of ASA during the first 16 weeks of pregnancy and the incidence of fetal
malformations.
 Antimicrobial therapy requires special onsideration during pregnancy and the
neonatal period. Tetracyclines cause tooth enamel dysplasia and inhibition of
bone growth. The sulfonamides, trimethoprim, and metronidazole may exert fetal
toxicity. Sulfonamides, by displacing bilirubin from serum albumin, may cause
kernicterus in neonates. Chloramphenicol may cause the “gray baby” syndrome.
 Fetal alcohol syndrome
o Ethanol use in pregnancy is associated with teratogenic effects, including
mental retardation, growth deficiencies, and charactertistic malformations
of the face and head.
The Drugs
Autonomic Drugs
 Anatomy and Physiology
o The nervous system is divided into the central nervous system and the
peripheral nervous system. The peripheral nervous system can be further
divided into the efferent division, neurons that carry signals away from the
brain (CNS), and the afferent division (information brought to the CNS).
The efferent portion is then divided into the somatic and autonomic


systems. The somatic system is involved in voluntary activities, such as
the contraction of skeletal muscles. The autonomic system is composed
mainly of visceral motor neurons and controls involuntary functions, such
as smooth muscle, cardiac muscle, and glands. It is the efferent autonomic
nervous system that is divided into the sympathetic and parasympathetic
nervous systems.
o Drugs affecting the autonomic nervous system are divided into two
subgroups according to the type of neuron involved in their mechanism of
action.
 Cholinergic drugs act on receptors that are activated by
acetylcholine.
 Adrenergic drugs act on receptors that are stimulated by
norepinephrine or epinephrine.
o All autonomic pathways consist of a preganglionic fiber and a
postganglionic fiber. Preganglionic fibers arise in the CNS and end at a
ganglion. Postganglionic fibers begin at a ganglion and end in the effector
tissue. Messages pass by means of chemical neurotransmitters from the
preganglionic to postganglionic fibers and then from the postganglionic
fibers to the receptors in effector tissues.
The Sympathetic Division
o Also known as the “fright, fight, or flight” or thoraco-lumbar division, the
preganglionic fibers here derive from the thoracic/lumbar division of the
spinal cord. This is the system activated “for emergencies.”
o Anatomically, the preganglionic fibers are short, and postganglionic fibers
are long. Most ganglia are located near the spinal cord. Nicotinic (Nn)
receptors are located at the pre/post-ganglionic synapse, and alpha and
beta receptors are located at the postganglionic fiber/ effector sites.
o The neurotransmitter between preganglionic and postganglionic fibers is
acetylcholine (Ach). Vesicles of acetylcholine are present at the terminus
of the preganglionic fiber. Neuronal impulse causes a number of vesicles
to fuse with the terminal membrane and release Ach which then attaches
to cholinergic receptors on the postganglionic fiber and the receptor
becomes activated. This creates an action potential in the postganglionic
fiber. Ach is then hydrolyzed by acteylcholinesterase very quickly.
o The neurotransmitter released from postganglionic fibers is
norepinephrine. Vesicles of norepinephrine are present at the terminus of
the postganglionic fiber. Neuronal impulse causes a number of vesicles to
fuse with the terminal membrane and release norepinephrine which
attaches to adrenergic receptors on cell surfaces of the end-organ.
Receptors become activated, bringing about (preventing) activation of
biochemical processes within the cell. The majority of norepinephrine,
like epinephrine is reabsorbed into the postganglionic fiber, while some is
metabolized by monoamine oxidase (MAO) or catechol-O-methyl
transferase (COMT).
The Parasympathetic Division



o This is also known as the cranio-sacral division. It includes cranial nerves
and is utilized in normal, vital, non-emergency situations. This
counterbalances the sympathetic system.
o Anatomically, preganglionic fibers are long, and postganglionic fibers are
short. Nicotinic (Nn) receptors are found at the pre/post-ganglionic
synapse, and muscarinic receptors are found at the postgalglionic fiber/
effector sites.
o The neurotransmitter found between both synapses is acetylcholine.
Acetylcholine is hydrolyzed very rapidly by acetylcholinesterase (true
cholinesterase, erythrocyte cholinesterase).
Synthesis of Neurotransmitters
o Catecholamines: Norepinephrine, Epinephrine, Dopamine
 Tyrosine enters the neuron and is converted to
dihydroxyphenylalanine (DOPA), which is then converted to
dopamine. Dopamine enters a storage vesicle and is converted to
norepinephrine via beta-hydroxylase. In the adrenal medulla, some
norepinephrine is converted to epinephrine in the cytoplasm.
o Acetylcholine
 Choline enters the neuron by active transport. Choline and acetyl
CoA then combine, catalyzed by choline acetyltransferase.
Acetylcholine is then actively transported into storage vesicles.
Autonomic Receptors
o Adrenergic receptors include Alpha and Beta receptors
 Alpha 1
 Alpha 2
 Beta 1
 Beta 2
o Cholinergic Receptors, including Muscarinic and Nicotinic receptors
 Muscarinic receptors
 M1 receptors increase intracellular calcium in the CNS.
 M2 receptors activate potassium channels in the heart.
 M3 receptors activate potassium channels in smooth
muscle and in secretory glands.
 M4 receptors activate potassium channels.
 M5 receptors increase intracellular calcium.
 Nicotinic Receptors
 Nm receptors are found in skeletal muscle tissue, which is
not part of the ANS. This stimulates motor end plates on
skeletal muscle cells.
 Nn receptors are found in autonomic ganglia, the adrenal
medulla, and the CNS. The function is to depolarize
postganglionic neurons, secrete adrenal catecholamines, as
well as other unknown CNS functions.
Mechanisms for increasing autonomic activities
o Direct stimulation of receptors, i.e., administering a drug.
o Promotion of neurotransmitter release


Stimulate postganglionic fibers, e.g. with nicotine which acts like
Ach.
 Promote norepinephrine release with amphetamine
o Inhibition of neuronal uptake of neurotransmitters (mainly in sympathetic)
 Inhibit uptake of norepinephrine with cocaine, a stimulant.
o Inhibition of neurotransmitter metabolism
 Inhibit metabolism of norepinephrine with pargyline. This is an
MAOI that inhibits the breakdown of norepinephrine.
 Inhibit metabolism of Ach with physostigmine. This increases
parasympathetic activity. An example is given with post-surgery to
help with decreased urine retention.
Mechanisms for decreasing autonomic activities
o Blockade of ganglionic receptors (e.g. with hexamethonium).
Transmission to both cholinergic and adrenergic postganglionic fibers is
inhibited. You can also use trimethaphan (Arforiad) and mecamylamine.
These are only used in emergency situations (i.e. aneurysms). This is rare
because it blocks the entire ANS.
o Inhibition of neurotransmitter synthesis. This is not a widely-employed
mechanism clinically.
o Inhibition of neurotransmitter release
 Guanethidine inhibits norepinephrine release and Botulinum toxin
inhibits Ach release.
o Inhibition of neurotransmitter storage
 Inhibit uptake of norepinephrine into vesicles with reserpine. This
is only with the sympathetic system.
o Blockade of peripheral receptors. This is the most common method. The
drugs listed above are used.
Cholinergic Drugs
 Cholinergic stimulants are also called cholinomimetic or parasympathomimetic
drugs. These mimic acetylcholine.
 Stimulants
o They act on receptors that are activated by acetylcholine. The
preganglionic fibers terminating in the adrenal medulla, the autonomic
ganglia, and the postganglionic fibers of the parasympathetic division use
acetylcholine as a neurotransmitter.
o Modes of action
 Direct
 Bind to muscarinic or nicotinic receptor
 Indirect
 Inhibit cholinesterase
o Autonomic Nicotinic (Nn) Receptors (Ganglionic)
 Endogenous acetylcholine. (Not exogenous)
 Nicotine
 Use- Overcome nicotine addiction/ insecticides

Adverse effects- hypertension, tachycardia,
vasoconstriction, salivation, CNS stimulation, convulsions
with respiratory arrest, or ganglionic blockade with
respiratory depression. It shuts down the ANS.
o Muscarinic Receptors
 Direct stimulants
 Muscarine
 Acetylcholine (Miochol)
o Used as a surgical miotic. Constricts bronchi and GI
musculature. Causes miosis.
 Metacholine
o For postoperative ileus or post-op urinary retention
 Pilocarpine (IsoptoCarpine)
o Used in treating POAG by causing miosis,
increasing aqueous outflow. It may also decrease
production of aqueous. Adies syndrome.
o Adverse effect- Local irritation
 Carbachol (Miostat)
o Used as a surgical miotic and treating POAG
 Bethanechol (Urecholine)
o Resistant to acetylcholinesterase (metabolized
slowly)
o Used in treating urinary retention and GI paresis
o Adverse effects- Sweating, NVD,
bronchoconstriction
 Contraindications
o Asthma, coronary insufficiency, ulcers,
hyperthyroidism.
 Cholinesterase inhibitors (Indirect Stimulants)
 Reversible, lasts 1-2 hours
o Physostigmine
 To treat phthiriasis palpebrum and
cholinergic blocker overdose
o Demecarium (Humorsol)
 To treat POAG (longer acting than
pilocarpine) and accommodative esotropia
o Neostigmine (Prostigmin) / Endrophonium/
Pyridostigmine
 To treat myasthenia gravis by increasing
Ach to flood available receptors.
 To treat neuromuscular blockade.
o Carbamates, alcohols
 Irreversible, due to covalent bonding
o Isoflurophate (Floropryl) / Echothiophate
(Phospholine)



To treat POAG and accommodative
esotropia
o Nerve gas, insecticides
Adverse Effects
o Miosis, salivation, sweating, bradycardia,
hypotension, NVD, rhinorrhea, convulsions, and
death due to respiratory depression.
o Treatment- Atropine and/or pralidoxine. This
unattaches cholinesterase and reactivates Achase.
o Uses
 Eye: glaucoma, accommodative ET
 GI/urinary tract: post-op ileus, urinary retention
 Neuromuscular: MG, relief of surgical neuromuscular block
 Cardiovascular: tachycardia
 Atropine, tricyclic antidepressant OD
Blockers
o These block the muscarinic synapses of the parasympathetic nerves. These
usually are beneficial in a variety of clinical situations.
o Mode of action:
 Receptor blockade or prevention of acetylcholine release.
o Systemic effects
 CNS- sedative effect, drowsiness, stops tremor, prevents vestibular
disturbance.
 Eye- mydriasis, cycloplegia
 Cardiovascular- tachycardia
 GI Tract- dry mouth, diminished intestinal tone
 Sweat glands- suppression of thermoregulatory sweating
o Uses
 CNS- Parkinson’s Disease, motion sickness
 Eye- cycloplegia, mydriasis, synechiae prevention
 GI Tract- peptic ulcer, diarrhea, gut hypermobility
 Cardiovascular- hyperactive carotid sinus reflex
 Respiratory- pre-anesthesia to prevent laryngospasm
 Cholinergic poison- insecticides, wild mushroom poisoning
o Toxicity
 Dry mouth, tachycardia, flushed skin, delirium, mydriasis,
agitation, fever
o Autonomic Nicotinic (Nn) Receptors (Ganglionic)
 Hexamethonium
 Mecamylamine (Inversine)
 Trimethaphan (Arfonad)
 Use- Decrease blood pressure in emergency situations only,
because it shuts down the entire ANS.
 Adverse effects- Urinary retention, GI atony (lack of tone),
cycloplegia, dry mouth, and orthostatic hypotension.
o Muscarinic Receptors (parasympatholytic drugs)



Tubocarine (Tubarine)
Belladonna Alkyloids
 Atropine
o Mechanism- Attaches to muscarinic receptors, but
does not activate them.
o This is extracted from the deadly nightshade/jimson
weed.
o Therapeutic dose is usually less than 1mg. Dosages
of about 1-2 mg are needed for CI.
o Uses
 Decrease secretions pre-operatively
 Cycloplegic refraction/ Mydriasis
 Treat amblyopia
 Treat anterior uveitis and posterior
synechiae
 Treat GI spasm
 Treat pulmonary edema
 Treat overdose of cholinergic stimulants
o Adverse Effects
 Excessive mydriasis, flushing (vasodilation
in blush areas), dry mouth, confusion,
urinary retention, tachycardia. (Dry as a
bone, red as a beet, mad as a hatter, and
blind as a bat).
 Scopolamine
o Uses
 Prevents motion sickness
 Produces mydriasis
o Produces more CNS activity than atropine
o Causes drowsiness (used as a sleep aid)
Synythetic Compounds
 Homatropine, Cyclopentolate, Tropicamide
o For mydriasis and cycloplegia
Adrenergic Drugs
 Adrenergic stimulants are also called sympathomimetic drugs. Adrenergic
blockers are also called sympatholytic drugs.
 Some drugs stimulate or block all adrenergic receptors, while some drugs affect
only certain adrenergic receptors but not others.
 Stimulants/ Agonists
o Drugs acting on Alpha-1 Adrenergic Receptors
 Phenylephrine (Neosynephrine)
 Actions- Vasoconstriction and mydriasis. Relieve nasal and
ocular congestion.
 Uses
o Inhibit washout of local anesthesia due to decreased
blood flow
o Treats shock by increasing blood pressure
 Methoxamine (Vasoxyl)
 Action- Vasoconstriction
 Uses- Treat shock
 Pseudoephedrine (Sudafed)/ Phenylpropanolamine
 This is a derivative of ephedrine. Ephedra (Ma Huang) is a
dietary supplement, but it is not under the same regulations.
This is very dangerous.
 Action- Vasoconstriction
 Use- Treat nasal congestion. This inhibits dilation of nasal
vessels that lead to taking up more space and releasing
fluid.
o Drugs Acting on Alpha-2 Adrenergic Receptors
 Action- these are presynaptic, so it is able to prevent the release of
norepinephrine from postganglionic sympathetic fibers. This
means less stimulation of alpha-1 receptors, therefore less
vasoconstriction. This is an important negative feedback
mechanism.
 Clonidine (Catapres)
 Part of the effect is in the CNS
 Use- Treat hypertension
 Adverse effects- Dry mouth, sedation, dizziness.
 Methyldopa (Aldomat)
 All of the effect is in the CNS
 Metabolized to the false transmitter alphamethylnorepinephrine, acting like norepinephrine, blocking
its activity.
 Uses- Treat hypertension
 Guanabenz (Wytensin)
 Guanfacine
o Drugs Acting Nonselectively on Alpha Receptors
 Norepinephrine
 Actions
o Vasoconstriction by causing negative feedback
o Increased cardiac contractile force (positive
inotropic effect)
o Increased cardiac rate (positive chronotropic effect)
o For shock
 Use- Inhibit washout of local anesthesia
 Methoxamine
o Drugs Acting on Beta-1 Adrenergic Receptors
 Dobutamine
 Increases cardiac contractile force
 Use- Treat cardiac failure (CHF)

o
o
o
o
Dopamine
 Increases cardiac contractile force, increasing output.
 Causes release of norepinephrine in the heart (positive
feedback)
 Use- Treat cardiac failure
 Norepinephrine
 Metoprolol (Lopressor), Atenolol, and Acebutolol.
Drugs Acting on Beta-2 Adrenergic Receptors
 Albuterol (Ventolin), Terbutaline (Brethine), Metaproterenol
(Metaprel)
 Butoxamine
 Action- Relaxation of bronchial smooth muscle
 Use- Treat bronchoconstriction (asthma) and decrease
blood pressure
 Ephedrine has been largely replaced by other agents.
 Salbutamol
Drugs Acting Nonselectively on Beta Receptors
 These are rarer now, because we have more selective agents.
 Isoproterenol (Isuprel)
 Actions
o Relaxation of vascular muscle (B2)
o Relaxation of bronchial muscle (B2)
o Increased cardiac rate and contractile force (B1)
 Use- Relieve bronchoconstriction, heart block, and
bradycardia.
 Propanolol, Nadolol, Timolol, and Pindolol.
 These can be used for HTN, angina, and glaucoma.
 Side effects include bronchoconstriction and heart failure.
Drugs acting nonselectively on all adrenergic receptors
 Epinephrine/ Norpinephrine
 Increases cardiac contractile force and heart rate
 Vasodilation: skeletal muscle, liver, GI tract
 Vasoconstriction: skin, mucosa, kidneys, veins
 Bronchodilation
 Urinary retention
 Mydriasis
 Reduction in IOP
 Decreases insulin secretion and increases glucagons
secretion
 Epinepherine, used for bronchospasm, allergic reactions, cardiac
arrest, etc.
 Ephedrine, used for bronchospasm, urinary incontinence, etc.
 Phenylpropanolamine
 Amphetamine, used for narcolepsy, ADD, etc.
Indirect-Acting Agents
 Amphetamine facilitates release of NE and inhibits uptake of NE





Cocaine prevents NE uptake
Tricyclic antidepressants prevent NE reuptake
Monoamine oxidase inhibitors prevent NE metabolism
Ephedrine facilitates release of NE, in addition to direct effects, by
directly stimulating A1.
o Actions
 Iris- A1- Dilation
 Ciliary Muscle- B: increase aqueous production
 Heart- B1- increase heart rate, contractility
 BV of skin, viscera, kidney- A1- constriction, B2- dilation
 Bronchial smooth muscle- A1- bronchoconstriction, B2bronchodilation
 GI tract- walls- B1- decreased motility
 GI tract- sphincter- A1- constriction
 GI tract- glands- A1 and A1 direct acting
 Ephedrine- B1- decreased secretions
 Direct- acting agonists act on alpha or beta receptors, producing
effects similar to stimulation of sympathetic nerves or release of
the hormone epinephrine from the adrenal medulla.
o Adverse effects of stimulants include HTN, cardiac arrythmias, and
tolerance.
Blockers
o Adrenergic antagonists bind to adrenoreceptors but do not trigger the usual
receptor-mediated intracellular effects. These drugs act by either
reversibly or irreversibly binding to the receptor, thus preventing their
activation by endogenous catecholamines.
o Drugs acting on Alpha-1 Adrenergic Receptors
 Prazosin (Minipress)
 Use- Treat hypertension
 First-dose phenomenon: marked postural hypertension.
(pass out when standing up)
 Terazosin (Hytrin)
 Treat HTN
o Drugs acting on Alpha-2 Adrenergic Receptors
 Yohimbine (Yocon) to stimulate the cardiovascular system
o Drugs acting nonselectively on Alpha Receptors
 Phenoxybenzamine (Dibenzyline)
 Irreversible, non-competitive blockade (covalent bonding)
 Adverse effect- Postural hypotension
 Phentolamine (Regitine)
 Reversible, competitive blockade
 Adverse effect- Postural hypotension
 Both of these can cause epinephrine reversal. It blocks epinephrine
therefore lowering blood pressure.
 This is used for HTN in pheochromocytoma. Side effects of
blockers include postural HTN and cardiac stimulation.
o Drugs acting on Beta-1 Adrenergic Receptors
 Metoprolol (Lopressor), Acebutolol (Sectral), Atenolol
(Tenormin), and Esmolol (Brevibloc)
 Relatively selective for beta-1 receptors, therefore less
likely to cause bronchoconstriction because it does not
block beta-2.
 Uses
o Treat hypertension
o Prevent attacks of angina pectoris (heart working
too hard)
o Drugs Acting on Beta-2 Adrenergic Receptors
 Butoxamine- this constricts the bronchi (no therapeutic use)
o Drugs Acting Nonselectively on Beta Receptors
 Propanolol (Inderal)
 Reversible
 Use- Treat hypertension
 Effects are more noticeable during exercise, when
sympathetic activity is high
o Prevents increase in heart rate and cardiac
contractile force
 Adverse effects
o Augmentation of insulin-induced hypoglycemia
o Heart failure
o Abrupt withdrawal may result in angina,
hypertension, tachycardia, or other dysrhythmias.
o Bronchoconstriction
 Nadolol (Cogard)
 Uses
o Treat hypertension
o Prevent attacks of angina pectoris
 Timolol (Blocadren, Timoptic)
 Uses
o Treat hypertension
o Prevent attacks of angina pectoris
o Reduce IOP, treat glaucoma
 Carteolol (Cartrol), Pindolol (Visken), Penbutolol (Levatol)
 Possess some beta agonistic ability, so cause less
bradycardia than other beta blockers.
 Use- Treat hypertension.
o Drugs acting Nonselectively on all Adrenergic Receptors
 Labetalol (Normodyne, Trandate)
 Use- Treat hypertension
 Adverse effects- Postural hypotension, nasal congestion,
and bronchospasm.
o Indirect-acting Agents- Inhibits adrenergic activity
 Reserpine (Ser-Ap-Es)
 Inhibits storage of norepinephrine
 Occassionally used to treat hypertension
 Guanethidine (Ismelin)
 Mechanisms
o Inhibition of release of norepinephrine by
displacing norepinephrine in vesicles
o False transmitter. This does not do anything. There
is no activation.
 Use- Moderate to severe hypertension
 Adverse effects
o IV administration can increase blood pressure
initially. This is because norepinephrine can be
displaced very fast, only for about 30 minutes. (So
don’t use with aneurysms)
o Postural hypotension
 Guanadrel (Hycorel): faster onset and offset
 Bretylium (Bretylol)
o Actions
 Cardiovascular
 A
o Lower TPR, BP, postural hypotension, reflex
tachycardia
 B
o Lower BP, slow heart rate, decrease contractability
 Respiratory
 A
o Nasal Stuffiness
 B
o Increased airway resistanec
 Eye
 A
o Reduced pupillary dilator tone
 B
o Reduce IOP
 Metabolic
 B- inhibit lipolysis
o Uses
 Alpha Blockers
 Management of adrenal tumor
 Hypertensive emergency; limited, most useful when
emergency is due to excess circulating levels of alpha
agonists
 Peripheral masospasms (Raynaud’s syndrome); cause
vasodilation of consticted vessels, but are not useful when
peripheral vasospasm is due to morphologic changes.


Urinary obstruction: cause smooth muscle contraction in an
enlarged prostrate or bladder base.
Beta Blockers
 HTN: lowers blood pressure due to many factors.
 Angina: reduces cardiac work and oxygen demand.
 Cardiac arrythmias: use for both supraventricular and
ventricular arrythmias. They increase atrioventricular node
refractory period and reduce ventricular ectopic beats
 Hyperthyroidism: block adrenoreceptors and inhibit
conversion of thyroxine to triiodothyronine (T3)
 Glaucoma: decreases production of aqueous humor.
Autonomic Drugs in the Eye
Sympathomimetics
Phenylephrine (Phenylephrine HCl, AK-Dilate, Neo-Synephrine, Mydfrin,
Spectrodilate)
 Mechanism of Action
o Directly stimulates alpha-1 receptors, while having a negligible effect on
beta receptors, causing the release of norepinephrine from the adrenergic
nerve terminals. No effect on accommodation.
o Actions
 Contracts the iris dilator muscle
 Constricts conjunctival arterioles
 Stimulates Mueller’s Muscle
 Reduces IOP
 Increases aqueous flow for two hours, then decreases it
 Little effect on accommodation
 Clinical Use
o Mydriasis for DFE or fundus photography.
 Maximal effect in 45-60 minutes. An increased concentration
might decrease this time, but there is no increased effect. No
statistical difference was found in amplitude of mydriasis between
2.5-10% solutions.
 There is generally no effect on accommodation.
 Duration is up to 7 hours. Degree of dilation is dose-dependent.
Light irides are more responsive. Pretreatment with a local
anesthetic enhances the effect.
o Used in combination with parasympatholytics for breaking posterior
synechiae
o Diagnostic testing in Horner’s syndrome
o Ocular decongestant in lower concentrations




Remember that phenylephrine will cause vasoconstriction and will
reduce conjunctival hyperemia, so evaluate this before instillation
of the drop.
o Prevention of iris cysts caused by echothiophate
o Temporarily treat ptosis
Dispensing Information
o 0.12% Solution. Seen in old OTC decongestants
o 2.5% Solution. The most common prepared. Used for mydriasis.
o 10% Solution- much more side effects.
o There is a very short shelf life. A brown solution indicates oxidation.
Adverse Effects
o Ocular
 Keratitis with chronic use. Transient stromal edema.
 Transient pain (irritation and discomfort due to a decreased pH).
 Lacrimation, allergic conjunctivitis.
 Rebound hyperemia after chronic use.
 Pigment dispersion with IOP spikes. Elderly patients may develop
transient pigment floaters in the aqueous humor 30-45 minutes
after instillation.
 The patient may become tolerant after chronic use.
o Systemic
 The major concern is a rise in systemic blood pressure.
 Most studies show that a 10% solution will cause a
transient rise in blood pressure with multiple doses in short
intervals. Also, the patients who died following instillation
of 10% solution were positive for cardiovascular disease.
 Other reported side effects include occipital headache, rupturing of
aneurysms, subarachnoid hemorrhages, ventricular arrhythmias,
and blanching of the skin.
o Adverse effects are enhanced by the use of atropine, tricyclic
antidepressants, MAOIs, reserpine, guanethidine, and methyldopa.
Contraindications
o 10% solution- use with caution in patients with cardiovascular disease,
aneurysms, orthostatic hypotension, and insulin dependent diabetes
mellitus.
o Patients taking MAOIs, tricyclics, guanethidine, methyldopa, and
reserpine.
o Use with caution in patient predisposed to angle closure glaucoma.
Hydroxyamphetamine HBr (Paredrine, Paremyd)
 Mechanism of action
o Releases norepinephrine from adrenergic nerve terminals. It inhibits the
metabolism of norepinephrine and reduces its reuptake into the adrenergic
nerve terminals. This is an indirect agent on the dilator.
o Actions
 Contracts the iris dilator muscle




 Constricts the conjunctival arterioles.
Clinical use
o Mydriasis for DFE or fundus photography.
 One could also use it for dilation of patients with narrow anterior
chamber angles since it can be easily reversed with miotics, due to
its indirect action.
 Maximal mydriasis occurs in 60 minutes, with a duration of 6
hours.
 This is better with younger patients.
o Differentiation of preganglionic from postganglionic lesions in patients
with Horner’s syndrome.
o Has more of an effect on the accommodative status than phenylephrine.
Dispensing Information
o 1.0% solution. Single entity formulation.
o Paremyd. In combination with 0.25% tropicamide.
Adverse Effects
o Ocular irritation is rare and there are no reported cases of systemic
involvement. Perhaps there could be transient systemic hypertension and
tachycardia.
Contraindications
o Same as phenylephrine, but due to its ineffectiveness in postganglionic
denervation and other properties, it is safer in high risk patients.
Cocaine
 Background
o From the erythroxylon coca plant.
 Mechanism of action
o Indirectly blocks the reuptake of norepinephrine and blocks neuronal
sodium channels.
o Actions
 Local anesthesia
 Vasoconstriction
 Tachycardia
 CNS Stimulation
 Mydriasis
 Clinical Use
o Mydriasis
 Maximum at 4-60 minutes with a duration of 6 hours.
o Diagnosis of Horner’s syndrome
o Debride the cornea if it is ulcerated, damaged, etc.
o Local anesthesia
 Dispensing Information
o Not available commercially in solutions. It is a controlled substance.
o 1-4%
 Adverse Effects
o Excessive stimulation of the CNS

o Respiratory failure
o Corneal pitting and erosion.
Relative Contraindications
o Cardiac disease
o Hyperthyroidism
Mydriolytics
Thymoxamine
 Mechanism
o Blockade of alpha-1 receptors
 Clinical Use
o Reverse drug-induced mydriasis more safely than cholinergic drugs
o Treat ACG
o Differentiate between ACG and OAG with narrow angles
 A reduction in IOP indicated ACG, no reduction indicates OAG
with narrow angles while a partial reduction could be a
combination.
o Produce miosis during extracapsular cataract extraction
 Adverse effects
o Transient stinging and conjunctival hyperemia.
 Contraindications
o Acute anterior uveitis.
Dapiprazole (Rev-Eyes)
 Mechanism
o Blockade of alpha-1 receptors in the dilator muscle.
 Clinical Use
o Reverse drug-induced mydriasis more safely than cholinergic drugs. This
is only used in extreme cases if vision is absolutely necessary or during
post-extracapsular cataract extraction.
o Treat ACG
 Dosage
o Dose- 2 drops followed by another 2 drops, separated by 5 min.
o It comes in 2 vials that need to be mixed. This is expensive and has a short
shelf-life.
o It works better in light eyes.
 Adverse Effects
o Transient stinging, burning, itching, and conjunctival hyperemia.
o Edema, chemosis, punctate keratitis, and possible headaches and
photophobia.
 Contraindications
o Acute anterior uveitis.
Parasympatholytics (Cycloplegics, Anticholinergics, Cholinergic
Antagonists)

Block the effects of acetylcholine at muscarinic receptor sites in the iris sphincter
and ciliary body. Competes with acetylcholine for receptor sites at neuromuscular
junction on sphincter-competetive antagonist. Effects are potentiated with use of
antihistamines, phenothiazines, and tricyclic antidepressants.
Atropine (Atropine sulfate, Isopto atropine)
 Background
o This oldest and most potent mydriatic and cycloplegic agent available is
derived from the bella donna plant. It is highly ionized, so it can be
difficult to penetrate certain surfaces.
 Clinical use
o Mydriasis
 Onset at 10 minutes. The maximum effect is seen at 25 minutes
and can last for 2 days. The duration of mydriasis lasts up to 10
days. These times can slightly vary due to dosage.
 Heavily pigmented eyes show slower onset and less mydriasis.
o Cycloplegic refractions in children
 Onset at 15 minutes. Maximum cycloplegia is arrived at in 160
minutes and lasts 42 hours. Duration of cycloplegia is up to 12
days. Heavily pigmented eyes show prolonged cycloplegia.
 The duration of cycloplegia is too long for adults
o Treatment of anterior uveitis.
 Relieves the ciliary muscle spasm to decrease pain. Also prevents
posterior synechiae and reduces the thickness and convexity of the
lens.
o Myopia reduction treatment. It can also prevent the progression of myopia
by decreasing the ciliary muscle tension (0.5-1D).
o Amblyopia penalization therapy. Decreases the VA in the good eye so that
fixation is forced with the amblyopic eye.
o Treatment of malignant glaucoma.
o Induces acute ACG. (A provocative test).
 Dosage
o Regimen: 3 gtt of 1% qid the day before, and 1gtt the morning of the
examination. Occlude the nasolacrimal duct.
o 0.5-1.0% ointment
o 1, 2, and 3% solutions
o Shelf-life is greater at lower temperatures and pH.
o Treatment of overdose is with physostigmine.
 Adverse Effects
o Ocular
 Allergic contact dermatitis, irritation, elevation of IOP in glaucoma
patients (the only cholinergic that does this), allergic conjunctivitis,
and keratitis.
o Systemic


Diffuse flush (dilation of the cutaneous blood vessels), thirst,
hallucination, confusion, anhydrosis, urinary retention,
tachycardia, death. This is dose related.
 Dry mouth is the first sign of toxicity.
Contraindications
o Care must be taken in patients with glaucoma, narrow angles, light colored
irides, Down’s syndrome, brain damage, or spastic paralysis.
Scopolamine (Hyoscine)
 Clinical use
o Mydriasis
 Mydriasis can last for 3-7 days. Maximum mydriasis is seen at 20
minutes and lasts about 90 minutes.
o Cycloplegia
 Cycloplegia can last for 5-7 days. Maximum at 40 minutes.
o Treatment of uveitis.
o This is better to use in patients that are sensitive to atropine. The patient
just must be more compliant, since it is used qid instead of qd.
 Dispensing information
o 0.25% solution
 Adverse Effects
o Ocular and systemic effects are the same as atropine. CNS effects are
more common. Can produce a “twilight sleep” which produces a semiconsciousness.
 Contraindications
o Same as atropine.
Homatropine (Hydrobromide)
 Clinical use
o Mydriasis
 Depending on the dosage, mydriasis can last for 1-3 days.
Maximum at 40 minutes.
o Cycloplegia
 Can last for 1-3 days
o Treatment of uveitis
 Dispensing Information
o 2 and 5% solutions
 Adverse Effects
o Ocular and systemic effects are the same as atropine.
 Contraindications
o Same as atropine
Cyclopentolate (Cyclogel)
 Clinical use
o Cycloplegic refractions in all age groups




This is the cycloplegic of choice. Average residual accommodation
after use is 1.5D. Maximum cycloplegia is in 30-60 minutes and
can last for 1 day.
o Mydriasis
 Maximum in 30 minutes. Can last for 1 day.
 Less mydriasis seen in darker colored irides.
o Treatment of mild cases of uveitis.
Dispensing information
o 0.5%, 1%, and 2% solutions.
 Kids may have CNS toxic reactions to the 2%, so this is reserved
for adults only.
o Greater than 1 year old: 1gt 1% x2 (5 minutes apart)
o Less than one year old: 1gt 0.5% x2 (5 minutes apart)
o Ophthalmic sprays are available. These are refillable sterilized atomizers.
 Hold the unit 5-10cm away from the eyes. The eyes can either be
open or closed. After spraying, have the patient blink a few times.
Wipe off excess solution. This is useful for both mydriasis and
cycloplegia.
 Use: 3.75mL 2% cyclopentolate, 7.5mL 1% tropicamide, and
3.75mL 10% phenylephrine to have a final concentration of 0.5%
cyclopentolate, 0.5% tropicamide, and 2.5% epinephrine.
Adverse Effects
o Ocular
 Transient stinging, rare allergic reactions, keratitis if there is an
overdose, conjunctival hyperemia, elevation of IOP in POAG
patients, lacrimation, and photophobia.
o Systemic
 More central nervous effects than atropine. Visual and tactile
hallucinations, disorientation, emotional disturbances, incoherent
speech, restlessness, drowsiness, ataxia, dysphagia, psychotic
reactions, dryness of mucous membranes, grand mal seizures, and
tachycardia.
 These effects are more common with the use of a 2%
concentration.
Contraindications
o Use with caution in children, debilitated patients, and in patients with
narrow angles.
Tropicamide
 Clinical use
o Drug of choice for ophthalmoscopy and fundus photography due to its
fastest onset and greatest amplitude in mydriasis of the
parasympatholytics.
o Generally red-capped bottles (anticholinergics  red cap usually)
however do not go by cap color; always read the label before instilling the
drop.



o Mydriasis
 Maximum at 30 minutes. Duration 6 hours.
 Effects are independent of iris color.
 Diabetic patients require phenylephrine also
o Cycloplegia
 Maximum at 30 minutes. Duration 6 hours.
 Accommodation recovers before mydriasis. Average residual
accommodation is 1.6D at 30 minutes and 2.4D at 40 minutes.
 Varying degrees of cycloplegia can occur, causing blurred visual
complaints.
o Pretreatment with a local anesthetic prolongs the actions
Dispensing information
o 0.5% and 1% solutions
o 0.25% combined with 1% hydroxyamphetamine HBr as Paremyd
o Brand names
 Mydriacyl, Spectrocyl, AKDilate, Tropiacyl, etc.
Adverse Effects
o Ocular- Transient stinging, elevation of IOP in POAG patients.
o Systemic- Extremely rare.
Contraindications
o Hypersensitivity to belladonna alkaloids
o Patients with narrow angles.
o Patients with peripheral iridectomy for previous angle closure.
Combinations
 Cyclomydril
o Clinical Use
 Not enough to really suppress accommodation, but it inhibits
cycloplegia enough to decrease the light reaction.
o Dispensing Information
 Contains Cyclopentolate (0.2%), Phenylephrine (1%), Boric acid,
BAK (0.01%), and EDTA
 Paremyd
o Clinical Use
 Routine mydriasis is easier, because it contains an adrenergic and
anticholinergic all in one.
 Possible advantages
 One drop (not two) needed?
 Less cycloplegia
 Shorter duration mydriasis, because less tropicamide and
hydroxyamphetamine not as strong as phenylephrine.
o Dispensing Information
 Hydroxyamphetamine (1%) and Tropicamide (0.25%)
o Adverse Effects
 Photophobia. Less accommodative paralysis.
o Contraindications

Same as for each of the individual drugs.
Alcohols
 Ethanol
o Concentrations in beverages
Beverage
% Ethanol
Serving Size
Volume of ethanol
Beer
4
12 oz (360ml) 15 ml
Wine
15
3 oz (90 ml)
15 ml
Whisky
50
1 oz (30 ml)
15ml
o Absorption
 Stomach- 20%
 Small intestine- duodenum- 80%
 Lungs
o Distribution
 Total body water- goes to where there is water
 Each ml raises the BAC 0.001-0.002%
o Metabolism
 90-95% metabolized
 Rate: 1/hour (above 0.10% BAC)
 Zero order
 < .10% depends on first order
o Alcohol dehydrogenase found in liver (first pass) and in gastric mucosa
 Ethanol  acetaldehyde  acetate
 Men more than women
o Excretion
 Urine
 Expired air: Air:Blood partition coefficient = 1:2100
 Basis of breathalyzer
o Effects of acute use
 CNS
BAC
Symptoms
0.02%
Impaired judgement
Increased reflex time
No feelings of inebriation
0.05%
Slight dizziness
Disinhibition
Increased self-confidence
0.10%
Emotional instability
0.15%
Muscular incoordination
Decreased ability to walk a
straight line
Confusion
0.20%
Diplopia
Staggering
Vomiting
Stupor
0.30%
Amnesia
0.40%
Unconciousness
0.50%
Rigor mortis/ Death
0.70%
Rigor mortis/ Death (with
tolerance)
 0.08% is the legal state limit
 Skin and mucous membranes: Dehydration
 Cools skin with evaporation
 GI Tract
 Low concentration (<10%): Stimulation of secretions
(acids)
 High concentration (>10%): Inhibition of secretions (acids)
and decreased motility.
 Cardiovascular system
 Changes in heart rate
o Low dose increases, high dose decreases
 Changes in blood pressure, vasodilator (decreased bp)
 Feels warmer, but body temperature drops faster.
 Kidneys: Diuresis due to decreased ADH secretion. Increased
urination
 Endocrine system
 Inhibition of ADH secretion
 Increased secretion of epinephrine
 Increased secretion of corticosteroids
 Treatment of an acute overdose
 Maintain respiration
 Maintain blood pressure
 IV fluid
 B6, because alcohol depletes it
o Effects of chronic use
 CNS
 Wernicke-Korsakoff Syndrome
o Psychosis, dementia, forgetfulness, hepatitis
 Cerebellar atrophy
 GI Tract: gastritis
 Esophageal varices
o Like varicose veins in the esophagus. They dilate
and bleed.
 Liver
 Hepatitis
 Cirrhosis- scar tissue formed
 Cancer- from chronic inflammation
 Biochemical effects









o Decreased NAD+ leads to increased synthesis of
lactate from pyruvate
o Increased fatty acid synthesis
o Decreased lipid oxidation, leading to fat
accumulation in hepatic tissues
o Decreased NAD+ may cause hypoglycemia and
ketoacidosis
o Decreased synthesis of clotting factors
o Increased blood to the liver, and plugs it up.
Cardiovascular System: cardiomyopathy (increased dose, means
increased mortality)
Kidneys: increased lactate caused decreased excretion of urate
(increased gout) and increased excretion of zinc and magnesium
Endocrine system
 Increased secretion of epinephrine
 Increased secretion of corticosteroids
 Decreased testosterone, especially in men.
Tolerance can be acquired
Dependence. Go through withdrawals
Addiction
Fetal alcohol syndrome
 Prenatal growth deficiency
 Postnatal growth deficiency
 Microcephaly
 Developmental delay or mental deficiency
 Fine motor dysfunction
 Short palpebral fissures
 Midfacial hypoplasia
 Epicanthic folds
 Cardiac defects
 All can occur partially or extensively
 Dose related.
Treatment of chronic alcoholism
 Alcoholics anonymous (best track record)
 Other forms of psychotherapy
 Disulfiram (Antabuse) blocks the catabolism of
acetaldehyde
o When the person drinks, they will feel
 Nausea
 Dizziness
 Drowsiness
 Hyperthermia
 General dysphoria
Probable Mechanisms





Fluidization of neuronal cell membranes- decreased rigidity
and increased ion flow
 Inhibition or enhancement of ion flows
 Biding to specific (GABAA?) receptors
Therapeutic uses
 Treat methanol poisoning
 Treat acute pulmonary edema (topical)
 Cooling agent
 Antiseptic
Methanol
o Metabolized to formaldehyde and formic acid (damages the ONH)
 CH3OH  CHOH  HCOOH
o Acute intoxication
 Symptoms
 HA
 Dizziness
 Vomiting
 Colic- abdominal pain
 Dyspnea
 Dimness of vision, can recover unless total LOV
 Treatment
 Sodium bicarbonate
 Ethanol
 Supportive treatment
Ethylene Glycol
o Treatment is similar to that for methanol exposure
o In antifreeze
o Kidney damage
Isopropanol
o Causes painful gastritis
o Metabolized to acetone
o Treat with dialysis
Drug Abuse
 Definitions
o Drug abuse: use of a drug without a medically valid reason. This is seen
with all drugs. The use of an illicit drug, or the excessive or nonmediacal
use of a licit drug.
o Tolerance: decreased response to a drug upon chronic use. This is closely
related to physical dependence. Metabolic tolerance may result from an
increase in the rate of metabolism of the drug. Functional tolerance results
from pharmacodynamic alterations.
o Habituation: a condition in which the user of a drug desires to continue its
use, but in which dependence has not necessarily developed.

o Dependence: A condition in which abrupt discontinuance of the drug will
result in a withdrawal (abstinence) syndrome.
 Psychological- precedes physical
 Psychological dependence consists of the compulsive use
of drugs to relieve or prevent the anxiety engendered by
their withdrawal.
 Physical- withdrawal symptoms
 Physical dependence consists of an altered state such that
the withdrawal of the drug causes physiological
disturbances.
 Addiction: both psychological and physical dependence.
o Addiction: The overwhelming desire to continue to use a drug.
o Designer drugs: illicitly synthesized compounds that have small struvtural
modification from standard drugs without any major changes in
pharmacodynamics.
CNS Depressants
o Opioid analgesics (Narcotics)- widely abused
 Drugs
 Heroin
 Morphine
 Codeine
 Pentazocine
 Meperidine
 Oxycodone (Oxycontinin)
 Tolerance to some opioids begins to develop within 3-4 days.
Addicion within 2 weeks.
 Very few abusers begin by using the opioid medically.
 Withdrawal syndrome
 Mild dependence: Runny nose, lethargy
 Severe dependence: Runny nose, muscle cramps and
soreness, diarrhea, restlessness, irritability, weakness,
vomiting, lacrimation, violent yawning, sweating, chills,
goosebumps, sneezing, tachycardia, HTN.
 Duration is about 7 days for heroin.
 Treatment of dependence
 Cold turkey- abrupt withdrawal
 Methadone maintenance
 Methadone withdrawal
o Gradual
o Abrupt- duration of withdrawal syndrome is about
21 days.
o Barbiturates and certain other sedative-hypnotics
 Tolerance can be marked- 10-20x the usual dose may be taken.
 Effects
 Small doses: relaxation

 Larger doses: lethargy, euphoria, incoordination, coma
 Death is due to respiratory depression
 Withdrawal syndrome: nervousness, insomnia, convulsions, death
 Flurnitrazepam (Rohypnol)
 “Roofies”
 Date rape drug
 Cause amnesia
 Colorless/odorless
o Ethyl alcohol
 Withdrawal symptoms
 Early: Tremor, anxiety, anorexia, insomnia, seizures
 Late: Confusion, disorientation, hallucinations,
hyperthermia, delirium tremors.
o Marijuana
 Effects: relaxation, drowsiness, decreased aggression, sometimes
decreased motivation, increased sense of well-being, impaired
short-term memory, enhanced sensory input
 Toxic effects: CNS depression can lead to accidents; carcinogens
can result in lung cancer; also conjunctival injection and
tachycardia. Decreased immune, paranoia.
 Has more interaction with the tissues than other drugs because
people “hold it in.”
 Active ingredient is delta-9-tetrahydrocannabinol (THC); this is
sometimes used as an antiemetic when other medications fail to
work. (Decreased nausea)
o Nitrous Oxide
o Solvents
 Ketones: Acetone, methylethylketone, glue, gasoline
o GHB (gammahydroxybutarate)
 Aka Fantasy, Liquid E
 CNS depression, decreased inhibition, increased GH
CNS Stimulants
o Caffeine
 Coffee contains about 100mg per cup
 Therapeutic uses
 Mild analgesic
 Affects the cortex, medulla, and spinal cord
 HA
 ADHD
 Acute intoxication: Insomnia, vomiting, cardiac arrythmias,
convulsions
 Dependence: withdrawal effects include HA and lethargy. It
depends on the dosage.
o Amphetamines
 Effects: euphoria, wakefulness, weight loss


Toxic effects: HA, confusion, delirium, violence, vomiting,
diarrhea, metallic taste, cardiac arrythmias, mydriasis, paranoia
o Cocaine
 Euphoria; acute tolerance (with only one administration), therefore
need to increase the dose each time. This makes it the most
addictive drug.
 Users generally prefer cocaine to food.
 More reinforcing than amphetamines
 Cause nasal constriction/ septum ulceration.
 Combination with ethanol: cocaethylene
 Intensifies and prolongs the effects of cocaine
 In coronary artery disease: multiplies the risk of sudden
death by 21.5.
 Increased incidence of heart attack and stroke.
o Nicotine
 Intense dependence (addiction)
 Withdrawal syndrome: Nervousness, insomnia, desire to use the
drug.
Hallucinogens
o MDMA (3,4-methylenedioxymethamphetamine, “Ecstasy”)
 Decreased inhibition to love.
 Reported to enhance the emotions and cause feelings of empathy
 Destroys neurons that release serotonin, which can be permanent
o LSD (Lysergic acid diethylamide)
 Mechanism: stimulates serotonin receptors in the midbrain,
causing decreased inhibition of sensory input. Colors and sounds
are more intense.
 Popular in the 60s
 Effects: Hallucinations (often involving synesthesia- senses
become confused, i.e. hear a color or see an odor), euphoria,
dizziness, drowsiness, weakness, fear of disintegration (“bad trip”
induced psychosis), fashbacks are possible later. The flashbacks
are brought about by external stimuli, i.e. flashing lights, etc.
 Some effects are due to sympathetic stimulation
 Some tolerance, and cross tolerance with psilocybin and mescaline
(other hallucinogenic drugs).
 No dependence
 Treatment of acute use: chlorpromazine and reassurance.
o Phencyclidine (PCP, phenylcyclohexylpuperidine, angel dust, monkey
dust, elephant tranquilizer)
 Effects: CNS stimulation (some parts) and depression (others),
euphoria, hallucinations, analgesia, disorientation, hyperthermia
(why they take their clothes off), nystagmus, catatonic rigidity,
blank stare.
 Potential long-term effects include schizophrenia-like state,
dysarthria (difficulty speaking. The brain is alright, but
there is a problem getting the signal to the mouth), and
persistent difficulty with short-term memory.
 “Inside-outer”
 Great muscular strength
 Surgical analgesia for some time (Now Ketamine is used).
 Death is usually due to drowning or to other kinds of accidents
 Due to confusion/hyperthermia.
o Nutmeg and Mace
 Mental aberrations, drowsy, nausea, vomiting
 Dose: 2 tablespoons in 4-5hr lasts 48 hours. Take with OJ or milk.
 Not worth it. Can be fatal.
o Bufotenim
 Colorado toad skin
 Squeeze the toad and collect secretions. Dry it and smoke it.
 If by mouth, destroyed by stomach. “Toad Lickers”- placebo effect
 100x potency as LSD. Use small doses.
o Peyote
 Cactus
 Ingredient: Mescaline
 Used by Native Americans in rituals.
Toxicology
 Definitions
o Toxicology: The study of poisons
o Poison: Any substance, which, when taken in a sufficient quantity,
produces an undesirable effect
 i.e. cyanide, arsenide, ricin
 There are no “non-poisons”
 Sources include drugs, households, industrial wastes, energy
conversion, and living organisms.
o Excess dosage of a drug, either accidental or intentional, results in an
exaggerated response to that drug. Drug toxicity may be severe and may
lead to respiratory depression, cardiovascular collapse, and/or death if the
drug is not withdrawn and adequate treatment instituted.
o A relative overdose of a drug may be seen in patients who for some reason
do not metabolize or excrete a particular drug rapidly enough or who are
particularly sensitive to the effects of a drug due to hypersensitivity or
idiosyncrasy. This type of overdoseage usually can be controlled by
reducing the dose or by increasing the interval between doses of the drug.
 Note that elderly or debilitated patients often required smaller
doses of drugs.
 General Principles of Treatment
o Acute poisoning (one large dose)
 Skin contact: Wash, neutralize
 Prevent absorption- induce vomiting
 Facilitate excretion- use a diuretic


 Administer an antidote
 Supportive care- hydrate, etc.
o Chronic poisoning
 Facilitate excretion
 Supportive care
 Administer an antidote
Carbon Monoxide
o Causes most fatalities per year.
o Harmful, because it binds hemoglobin.
o Sources
 Automobile exhaust
 Cigarettes
 Gas and oil furnaces
o Mechanisms
 Prevents binding of nitric oxide and oxygen to hemoglobin
 Inhibits release of oxygen from hemoglobin, so its not released to
parts needed
o Acute poisoning
 Signs and symptoms
 HA (10-20%)
 Weakness (30%)
 Dizziness (30%)
 Collapse (40%)
 Increases in heart rate and respiration (50% bound)
 Coma (60%)
 Depression of cardiac and respiratory functions (70%)
 Treatment
 Fresh air or oxygen. Pure oxygen is best. Half life is 45
min.
 Artificial respiration
 Complete rest
 No exercise or caffeine, because these increase the need for
oxygen.
o Chronic poisoning
 Signs and symptoms
 Confusion, dizziness
 ECG abnormalities
 Visual impairment
 Treatment: Avoid further exposure. Breathe clean air
Cyanide
o Very rapid
o Sources
 Pits and leaves of stone fruits
 Fumigant
o Mechanism: Inactivation of cytochrome oxidase, so cells cant use oxygen

o Signs and symptoms
 Burning of throat
 Feeling of suffocation; hyperpnea
 Collapse
 Convulsions
 Bitter almond odor of breath
o Treatment (ASAP)
 Sodium nitrate i.v.
 Converts hemoglobin  Fe3+ (methemoglobin) to activate
cytochrome oxidase
 Sodium thiosulfate i.v.
Lead
o Heavy metal (like arsenic, Hg, Fe)
o Sources
 Automobile exhaust
 Dried, peeling paint
 Printer’s type and colored inks
 Certain ceramic glazes
 Many others
o Handled like calcium in the body
o Mechanism: Binds to sulfhydryl groups on proteins (enzymes). This
interferes with heme synthesis
o Acute poisoning
 Signs and symptoms
 Abdominal pain
 Diarrhea or constipation
 Vomiting
 Metallic taste
 Anemia
 Weakness
 Treatment
 Protein if lead was ingested (egg white, milk, meat)
 Calcium disodium EDTA
 Succimer
 Penicillamine
 Supportive care
o Chronic poisoning
 Signs and symptoms
 Burtonian gum line- blue/gray line along gum margins
 Metallic taste
 Vomiting
 Weakness
 Lead encephalopathy
o Insomnia
o Irritability




o HA
 Anemia
Treatment
 Calcium disodium EDTA
 Succimer
 Penicillamine
 Supportive care
 Protein does not help.
Parathion
o Metabolized to paraoxon (irreversible cholinesterase inhibitor)
o Mechanism: Inhibition of acetylcholinesterase
o Acute poisoning
 Signs and symptoms
 Salivation
 Dimness of vision
 Paralysis of accommodation
 Confusion
 Convulsions
 Respiratory distress
 Treatment
 Atropine
 2-PAM
 Anticonvulsants
 Supportive care
Carbon Tetrachloride
o Industrial fat solvent
o Made worse by agents that increase CT metabolism
o Metabolism
 To carbon trichloride free radical
 Toxicity is increased by Phenobarbital use
o Effects
 CNS (acute): Drowsiness, Incoordination, Coma
 Ocular: Dulling of the cornea
 Liver (chronic): Centrilobular necrosis, Hepatic cancer
Iron
o Acute poisoning
 Major source: Iron medications (Usually FeSO4-sulfate)
 Usual victims: Children
 NVD, drowsiness (1hour)
 Apparent recovery sometimes occurs (5-7hr)
 Cardiovascular collapse (10-30hr)
 Coma
 Death (20hr)
 Treatment: Deferoxamine (Desferal)
o Chronic poisoning





Hemochromatosis
Cirrhosis
DM- temporary
Hyperpigmentation of the skin
Treatment: Deferoxamine (Desferal)
Vitamins
 Fat soluble vitamins
o These are more stable, more extensively stored in the body, frequently
toxic when over-consumed, less readily absorbed than water-soluble
vitamins.
o Vitamin A- Retinoid, 11-cis-retinal, all-trans-retinol, retinoic acid,
retinaldehyde, and beta carotene.
 Active form: retinol
 Beta carotene is provitamin A
 Functions
 Maintain epithelial cells, e.g lens epithelium
 Control mucus production
 Control keratinization
 Mediate dark adaptation
 Antioxidant
 Reconstituting the eye pigment needed for light perception,
maintaining the health of mucous membranes, normal bone
growth, and reproduction.
 Deficiency symptom
 Epithelial defects in the lens (cataracts)
 Deficiency in dark adaptation- nyctalopia
 Xerophthalmia- dry eyes
 Keratomalacia
 Perivasculitis
 Blindness
 Epidermal keratinization
 Abnormalities of mucous membranes
 Digestive disturbances
 Repisratory infections
 Dwarfism
 Brain damage in infants
 Infertility or spontaneous abortion
 Source
 Dark green, yellow, or orange vegetables and fruits, and
liver.
 Uses
 Doses: 650-2,000 IU/day
 Treat deficiency
 Dry eyes



Acne
Cancer prevention and treatment.
RP
o 15,000 IU/day
o drops with vitamin A probably do not help.
 Adverse effects
 Dry skin, itching, cracked lips, HA, papilledema.
 Increased pressure within the skull, abnormalities of skin
and hair, abnormalities of bone and muscles, liver damage,
abnormal fetal development.
 Hypervitamintosis A with >200,000 IU/day
 Acute: HA, N, V, blurred vision, peeling of the skin
 Chronic: liver damage, hypercalcemia, hyperlipidemia, and
death.
o Vitamin E
 Active form: d-alpha-tocopherol
 Function: antioxidant and anti-inflammatory
 Important in child-bearing
 Deficiency symptoms
 Possible decreased stability of erythrocytes
 Neurologic abnormalities, axonal degeneration possible
 Ophthalmoplegia
 Pigmented retinopathy
 Abortion in females
 Sources
 Wheat germ oil
 Use: treat deficiency, treat intermittent claudication, prevent
retrolental fibroplasias caused by oxygen in premature babies
o Vitamin D
 Most active form: Calcitrol; Cholecalciferol (D3) is converted to
calcitrol in the body; Calciferol (D2) is also active. Activated by
UV.
 Function: regulate calcium and phosphate concentrations by
facilitating calcium reabsorption from the intestines.
 Deficiency symptoms
 Children: rickets. Bones so weak that the skeleton is
deformed.
 Adults: osteomalacia
 Sources
 Vegetable oils, wheat germ, whole wheat products
 Use: treat definiciency
 Adverse effects
 This is much less toxic than the other fat soluble vitamins.
 May cause blood clotting problems, abnormal liver
function, slow wound healing in very large doses.


Weakness, HA, GI distress, calcification of soft tissues
especially the kidneys heart and vessels, fatigue, NVD,
hypercalcemia. Arrested growth.
o Vitamin K
 Active form: phytonadione, menaquinones
 Function: mediate synthesis of several clotting factors
 Deficiency symptoms: excessive bleeding tendency
 Sources
 Leafy green vegetables. Also made by gut bacteria and
absorbed in the bloodstream.
 Uses
 Treat deficiency
 Treat overdose of oral anticoagulant. Required for normal
blood clotting.
 Adverse effects
 Flushing, dyspnea, and intravascular coagulation.
Water soluble vitamins
o Vitamin C (Ascorbic acid, ascorbate)
 This is an antioxidant, involved in the manufacture of collagen.
Also assists in the manufacture of thyroid hormones, absorption of
iron and calcium from the intestines, and maintaining the health of
adrenal glands.
 Actively transported into the eye. 20x greater concentration
 Functions
 Facilitates absorption of dietary iron
 Cofactor in several enzymatic reaction
 Antioxidant
 Preservative
 Deficiency results in scurvy
 Appetite loss, irritability, soreness of the arms and legs,
pain upon movement, and hemorrhages. New wounds
refuse to heal and old ones re-open. Gums swollen and blue
and ultimately teeth fall out.
 Use
 Treat scurvy
 Increased need following physical trauma
 Requirements and Sources
 Adults 60mg/day
 Found in citrus fruits, tomatoes, potatoes, leafy vegetables,
and liver.
 Adverse effects: diarrhea (acute and chronic), as well as physical
dependence.
o Vitamin B1 (Thiamine)
 This is a part of coenzyme thiamin pyrophosphate (TPP), an
essential ingredient in dozens of biochemical reactions that have to
do mostly with releasing energy from carbohydrates. Also shown
to be necessary for healthy functioning of the brain and nerve cells.
 Functions
 Metabolism of carbohydrates
 Maintain neuronal tissues
 Deficiency results in beriberi
 Beriberi is a disease of paralysis, heart failure, and death.
 Edema
 Cardiac failure
 Wernicke’s encephalopathy and Korsakoff syndrome
(impaired sensory and motor reflexes)
 Nystagmus
 Ophthalmoplegia
 Mental deterioration
 Alcoholic polyneuritis in alcoholics
o There is a strong correlation between alcoholism
and thiamin deficiency.
 Requirements and Sources
 Increase caloric requirement, then increase thiamin as
needed.
 Whole-grain enriched cereals and breads, dried legumes,
and pork products.
 Uses: treat deficiency
o Vitamin B2 (Riboflavin)
 In the form of coenzymes FAD and FMN. It participates in the
release of energy from carbohydrates, fats, and protein. Also
necessary for the activation of folacin, and aids in the cconversion
of tryptophan to niacin.
 Function: metabolism of fats, carbohydrates, and proteins
 Deficiency symptoms
 Sore throat, angular stomatitis, cheilosis, photophobia,
corneal vascularization, decreased VA, KCS, and cataracts.
 Cheilosis, angular stomatitis, glossitis, corneal
vascularization, photophobia, dermatitis
 Swollen, inflamed lips with cracks at the corners of the
mouth, depression, hypochondria, scaly skin rashes,
reduced muscular strength, and irritation of the eyes.
 Use: treat deficiency
 Requirements and Sources
 Requirement increases with energy needs.
 Found in liver, dairy products, meats, whole or enriched
grain products, spinach, and asparagus.
o Vitamin B3 (Niacin, nicotinic acid, nictinamide)
 In the form of coenzyme NAD and NADP. It is required by all
living cells. Plays a key role in the release of energy from all three
energy building nutrients (carbohydrates, fats, and proteins). Also
involved in the synthesis of protein, fat, and DNA.
 Function: metabolism of fats and carbohydrates
 Deficiency: pellagra
 Diarrhea, dementia, and dermatitis, then death.
 Lassitude, anorexia, weakness
 Requirement and Source
 Increase requirement with increased caloric needs
 Niacin can be produced from tryptophan and pyridoxine in
the body.
 Found in meat, poultry, legumes, peanuts, and enriched
grain products
 Use
 Treat deficiency
 Hyperlipoproteinemia
 Hypercholesterolemia
 Adverse effects
 Flushing
 Postural hypotension
 Itching
 NVD
 Peptic ulcer
o Vitamin B5 (Pantothenic Acid)
 Functions
 Metabolism
 Hemoglobin formation
 Steroid synthesis
 Deficiency results in
 Neuromuscular degeneration
 Steroid deficiency
o Vitamin B6 (Pyridoxine, pyridoxal, pyridoxamine)
 This is a part of a coenzyme called pyridoxal phosphate which
functions in many biochemical functions such as protein synthesis
and production of antibodies. Also important for healthy
functioning of the brain and nerves.
 Active: pyridoxal phosphate
 Function: coenzyme for
 Hemoglobin formation
 Amino acid and protein metabolism
 Deficiency symptoms
 Anemia, dermatitis, cheilosis, glossitis, stomatitis, and GI
distress
 Greasy, scaly rashes on the face, cracks at the corners of
the mouth, and a red, sore tongue, along with mental
depression and confusion.

Causes of deficiency
 Poor diet, isoniazid, hydralazine, and penicillamine.
 Requirement and Sources
 Greater amounts are needed by people on high-protein
diets, on alcohol, smokes, or on oral contraceptive pills
 Found in meat, liver, whole-grain products, egg yolks,
bananas, and vegetable
 Use: treat deficiency
 Adverse Effects
 Peripheral sensory neuropathy and physical dependence
o Vitamin B12 (Cyanocobalamin)
 Stored in the liver. B12 is necessary for folacin activity. Required
for building nerve tissue.
 Functions
 Regulate carbohydrate metabolism
 Production of red cells
 Production of lipids, amino acids, and nucleic acids
 Absorption mediated by intrinsic factor in parietal cells of the GI
tract
 Deficiency symptoms (seen in Vegans)
 Megaloblastic anemia (and pernicious)
 Neurologic damage: demyleination, paresthesias, loss of
deep tendon reflexes, loss of memory, confusion,
nystagmusm and loss of central vision
 Nerve, spinal cord, and brain damage, platelet
abnormalities.
 Deficiency is rarely due to inadequate dietary intake.
 Use: treat deficiency
 Requirement and Sources
 11 years and older need 3.0 ug/day.
 Found in liver, meat, fish, eggs, and dairy products, except
butter.
o Biotin
 Acts as coenzyme for reactions involved in the synthesis of protein
and fatty acids, and oxidation of fats and carbohydrates.
 Function: metabolism of amino acids and fatty acids
 Deficiency symptoms
 Hair loss, dermatitis, and neuromuscular disorders
 Depression, appetite loss, extreme weariness, sleepiness,
muscle pains, nausea, vomiting, hair loss, scaley skin, and
muscle atrophy.
 Common in pregnant women, alcoholics, children with
severe burns, elderly people, and athletes.
 Use: treat deficiency
 Requirements and Sources



100-200ug/day for adults and 35-85ug/day for children.
Found in organ meats, egg yolk, nuts, legumes, and whole
grains.
o Folic Acid
 Involved in several biochemical reactions such as assisting in the
manufacture of nonessential amino acids and synthesizing the
building blocks for DNA and RNA. To be biochemically active,
folacin must be combined with PABA.
 Function: synthesis of DNA and hemoglobin
 Deficiency symptoms
 Megaloblastic anemia
o Low blood hemoglobin, weakness, paleness, and
shortness of breath.
o Occurs frequently in pregnant women, especially
teenagers, alcoholics, and from certain drugs.
 Teratogenesis: neural tube defects
 Use: treat deficiency
 Requirement and Sources
 Liver, oranges, spinach, other green vegetables, and the
germ and bran portion of grains.
o Panthothenic Acid
 Component of coenzyme A, which participates in many reactions
such as those that yield energy from carbohydrates, fat, and
protein.
 Deficiency
 Irritability, restlessness, fatigue, mental depression, muscle
cramps, loss of coordination, appetite loss, V, D, skin
rashes, increased susceptibility to infections, and “burning
feet.”
 Requirements and Sources
 2-4mg/day for children and 4-7mg/day for adults
 Found in liver, dairy prodcts, meats, collards, potatoes,
broccoli, and royal jelly.
Macrominerals
o Calcium
 It is needed for the formation and maintenance of bones and teeth.
It is recommended for menopausal women and the elderly, because
of osteoporosis.
o Phosphorous
 Recommended daily requirements is 800 mg. Deficiencies are
unknown.
o Magnesium
 Recommended daily requirement is 300-350mg, which is easily
met with a normal diet.
o Sodium, Potassium, and Chloride


No recommended daily allowances because all three minerals are
so abundant in food, such as NaCl or KCl.
Microminerals (Trace Elements)
o Iron
 Important for oxygen transport (Hb) and other critical biological
processes. RDA is 18mg for women and a little less for men.
 Deficiency: Anemia
 Use: treat iron deficiency anemia
 Toxicity
 Acute: necrotizing gastroenteritis, shock, metabolic
acidosis, coma, and death
 Chronic: hemochromatosis, hepatic cirrhosis.
o Zinc
 Functions
 Prevent oxidation (an antioxidant)
 Aid wound healing (in antiseptics)
 Convert retinol to retinal
 Deficiency symptoms
 Night blindness
 Decreased color perception
 Hyperkeratinization of lid margins
 Blepharitis
 Conjunctivitis
 Photophobia
 Use: treat deficiency
 Sources
 Animal proteins and certain vegetables (potatoes, dried
peas, and beans).
o Selenium
 Function: prevent oxidation
 Deficiency in cardiac dysfunction
o Copper
 Function: prevent oxidation
 Deficiency symptoms
 Anemia
 Psychomotor dysfunction
 Skin lesions
 Bone lesions
 Adverse effects
 Systemic
o GI distress, myalgia, coma, death
 Ocular
o Kayser-Fleischer rings and sunflower cataracts
 Sources
 Many grains
o Iodine
 Deficiency is endemic goiter (enlarged thyroid gland). Iodized salt
is a good source of iodine.
o Fluoride
 Important in preventing tooth decay in children. Drinking water
supplies the daily amount of fluoride.
Ocular Toxicology of Systemic Drugs
 Determinants of Adverse Effects
o Dose
o Nature of the drug
o Route of administration
o Pathophysiologic variables
o Age and sex
o Multiple drup use
o History of allergy
o Idiosyncrasy
o Other drugs or chemincals to which the patient is exposed.
 Cornea and Lens
o Chloroquine and hydroxychloroquine
Antibacterial Drugs
Steroid-Antibiotic Solutions and Suspensions





Indicated for steroid responsive inflammation when bacterial infection or risk of
infection exists.
Dosage
o Usually q3-4h, then taper as inflammation subsides
o Ointment- do not prescribe more than 8g initially
o Solution of suspension- store upright; shake before instillation. Do not
prescribe more than 20ml initially.
o Do not refill without a re-evaluation.
Blephamide/ Vasocidin (Suspension, solution, or ointment)
o Sulfacetamide-prednisolone
o Dosage
 Suspension or solution- Instill 1-2 drops q1-6 hours, depending on
severity
 Ointment- Apply qd-qid.
o Ocular indications
 Inflammatory conditions of the palpebral and bulbar conjunctiva,
cornea, anterior segment, and contact dermatitis (when risk of
bacterial infection is low).
Bleph-10 (Sulfacetamide)
o 10, 15, and 30% solution
o 10% ointment
o Broad spectrum
o Staph and pseudomonas resistant
o STINGS.
Pyrimethamine Daraprim and Trimethoprim (Bactrim, Bactrim DS, Septra)
o Mechanism of action
 Inhibit dihydrofolate reductase, which catalyzes the reduction of
dihydrofolic acid to tetrahydrofolic acid. Folic acid cannot be
synthesized. Cells cannot also synthesize thymidine, purines, and
several amino acids. This works in synergy with sulfonamides to
increase the range of activity against microorganisms.
 Resistance is via either reduced bacterial cell uptake or alteration
of dihydrofolate reductase.
o Trimethoprim-Sulfamethoxazole Combination (Co-trimoxazole, Bactrim)
 Bactericidal
 Uses- UTI, prostatitis due to enterobacteriacaea, gonorrhea,
bronchitis caused by H. influenzae, Moraxella, and S. pneumoniae,
otitis media in children, and sinusitis
 Adverse effects
 All of the above
 Glossitis- inflammation of the tongue
 Stomatitits- inflammation of the mouth
 HA
o Pyrimethamine
 A 2,4-diaminopyrimidines



Antimalarial agent. Used in combination with asulfonamide
(sulfadiazine). It is effective against acute attacks of chloroquine
resistant P. falciparum malaria and as a prophylactic and
suppressive drug for P. Vivax malaria
 Used in combination with sulfadiazine or with triple sulfonamides
(sulfadiazine, sulfamerazine, and sulfamethazine). It is useful in
treatment of toxoplasmosis.
 Side effects
 Higher than the recommended dosage of 25mg can cause
drug induced folic acid deficiency resulting in depression
of WBC and platelets, as well as megaloblastic anemia.
o Trimethoprim (Trimpex)
 Bacteriostatic
 A 2,4-diaminopyrimidines
 Used in combination with sulfamethoxazole (synergistic effect).
Alone, not effective against Pseudomonas, so combine with
polymyxin B. do not use alone.
 Dosage is bid, po. Absorbed well when ingested orally.
 Good for kids greater than 2 months.
 It is beneficial for the treatment of Pneumocystic carini
pneumonitis and for the treatment of adults with shigellosis, UTI,
acute otitis media, and acute exacerbations of chronic bronchitis
associated with H. flu and S. pneumoniae.
 Used alone in the treatment of initial, uncomplicated UTIs.
 Trimethoprim-polymyxin B (antibacterial solution) (Polytrim)
effective in the treatment of surface ocular bacterial infections,
acute blepharitis, acute conjunctivitis, drug of choice in pediatric
eye infections, especially useful for patients allergic to
sulfonamides (no cross sensitivity).
 Polytrim 1 drop q3h while awake.
 Side effects
 Generally mild.
 At the recommended dosage, may precipitate hematologic
reactions (anemia) in patients who are initially deficient in
folic acid.
 Typical skin reactions produced by sulfonamides.
 N, V, Diarrhea, transient bilateral myopia, phototoxicity.
Ointments
o Hydrocortisone + Neomycin + Bacitracin + Polymixin B
 AK-Spore H.C., Cortisporin, Generics
o Prednisolone acetate + Gentamicin
 Pred-G, SOP
o Dexamethaone + Neomycin + Polymixin B
 AK_Trol, Dexacine Ung, Generics, Maxitrol ung
Solutions and suspension
o Hydrocortisone + Neomycin + Polymixin B

AK-Spore HC Ophthalmic suspension, Cortisporin suspension,
Poly-Pred suspension, Generics
o Prednisolone + Gentamicin
 Pred-G Suspension
o Dexamethasone + Neomycin
 Suspensions also contain Polymixin B
 NeoDecadron Solution, Maxitrol Solution, Poly-Dex Suspension.
Drugs Used in Treating Tuberculosis
 Inhibitors of protein synthesis
o Streptomycin, Kanamycin, and Amikacin
o Rifampin (Rifadin)- Inhibits DNA-directed RNA polymerase (turns body
secretions red)
o Capreomycin (Capastat)- Prevents translocation of peptidyl-tRNA on
ribosomes
 Inhibitor of cell wall synthesis- Cycloserine
 Isoniazid (Laniazid, INH)- Unknown mechanism
 Ethambutol (Myambutol)- Unknown mechanism
 Para-aminosalicylic acid (Teebacin)- Competes with PABA in folate synthesis
Drugs Used in Treating Leprosy
 Dapsone and Clofazimine (Lamprene)
Ocular Lubricants

Artificial Tears
o General Information
 Inorganic electrolytes
 Preservatives
 Some preservatives are inactivated upon contact with the
tear film. Unit-dose formulations are preservative free.
 Polymers (water coluble)
 To increase wettability of corneal surface, extend adhesion,
and increase conjunctival sac retention time
 Viscoelastic agents
 Electrolytes (Ca, Na, P, Mg, etc)
o Uses
 Decrease mechanical lid trauma, wash out toxins, increase tear
volume, increase corneal wetting, and act as an environmental
barrier.
o Cellulose Ethers
 Agents
 Methylcellulose (MC)
 Hydroxyethylcellulose (HEC)



 Hydroxypropylcellulose (HPC)
 Hydroxypropylmethylcellulose (HPMC)
 Carboxymethylcellulose (CMC)
 Increase viscosity. They are also used to moisten contact lenses
and to prolong contact time of ophthalmic solutions with the eye.
 Essentially inert chemically and pharmacologically. This means
that there are no actions to produce any side effects.
o Polyvinyl Alcohol (PVA)
 Enhances contact time of ophthalmic solutions. This is seen more
in contact lens solutions. It is much less viscous than MC, so it is
thickened or gelled by sodium bicarbonate, sodium borate, sodium
sulfate, potassium sulfate, and zinc sulfate.
o Other polymeric systems
 Polyvinylpyrrolidone (PVP, povidone)
 Forms a hydrophilic, mucomimetic layer that adsorbs to the
epithelial surface. This provides a “smooth curtain” that
decreases irritation with each blink.
 Polycarbophil- Longer retention time than PVA or CMC
o Other ingredients of artificial tear preparations may affect the surface
activity
o Similsan
 Also a derivative of belladonna
 For allergies
o Non-preserved tear preparations (i.e. Genteel)
 Preserved with Sodium preborate that become sodium borate and
H2O2 in the eye. Preservatives tend to increase epithelial
permeability, so non-preserved solutions avoid epithelial damage
and disruption of the tear film stability.
 Uses
 KCS and application of gonioscopic lenses
 Disadvantages
 Higher cost than preparations containing a preservative.
o Dosage- q4-6h or prn.
Cyclosporine (Restasis)
o An immunosuppressant
o Applied topically. Comes in a 0.05% emulsion, used bid.
o Use only in those greater than 16 years.
o Very expensive
Ointments and Gels
o Contain petrolatum (petroleum jelly), lanolin, and/or mineral oil. Dissolve
at temperature of the eye and disperse with tear film. Usually preservative
free.
o Dosage: at bedtime or prn. Applied to the lower cul-de-sac. Always apply
before instillation of a solution.
Artificial Tear Insert (Lacrisert)
o Hydroxypropylcellulose rod (dry)




o Placed in the inferior cul-de-sac
o Dissolves over 6-8 hours in the fluid from the conjunctival circulation. It
is very difficult to dissolve in a dry eye.
o Adverse effects
 Blurring and FBS
Lacrimal Occlusive Devices
o Prevent the drainage of aqueous. Good if there is a decreased amount of
aqueous.
o Collagen rods
 Preparations
 Collagen implant
 Temporary intracannalicular collagen implant
 Dissolves in 4-7 days
o Silicon-based plugs
 Preparations
 Freeman punctum plug
 Herrick lacrimal plug
 Longer-lasting than collagen rods
 Topical anethstic may be required for insertion
Viscoelastic Agents
o These are used in extreme cases to maintain ocular volumes
o Sodium Hyaluronate
 A polysaccharide polymer with a very high viscosity
 Uses
 Dry eyes
 Intraocular surgical procedures
 Preparations: 0.1% buffered solutions
o Chondroitin Sulfate
 A polysaccharide polymer with a very high viscosity
 Use to treat KCS and anterior segment diseases
 Preparation: Viscoat (also contains sodium hyaluronate).
Oral Therapy
o Omega-3 Essential Fatty Acids and Flaxseed Oil
Vitamin A Derivatives (Vita-A drops)
o Ocular manifestations of deficiency, such as epidermal keratinization and
squamous metaplasia of mucous membranes can be alleviated by systemic
or topical administration
o Forms that are of therapeutic value include tretinoin (all-trans retinoic
acid), retinol, and retinoic acid analogs
o Preparations
 Ointments, solutions, capsules and tablets for systemic use, gels.
 Included in some artificial tears preparations
o Adverse Effects (ung)
 Transient hyperemia, irritations, and burning, decreased VA, and
entrapment .
Ocular Vasoconstrictors/Decongestants



Topical Decongestants
o Formulated with adrenergic agonists such as naphazoline and
tetrahydrozoline and oxymetazoline. Reduce symptoms. Various brand
names are available. Available OTC because the concentration is low.
There is generally no mydriasis.
o This provides only palliative treatment.
o Greater alpha than beta receptor activity.
o Relative fast onset of action.
o Dosage generally qid initially, decreased to bid with improvement if
symptoms.
o ADRs
 Chronic use leads to loss of efficacy, rebound hyperemia and
exacerbation of symptoms.
 Mydriasis.
 This is seen more with corneal abrasions and hypersensitivity.
o Contraindications
 Cardiovascular disease, DM, corneal disease or trauma, HTN,
hyperthyroid, narrow angles.
Phenylephrine (Prefrin Liguifim, Relief, Zincfrin)
o Oldest of the decongestants
o Mechanism
 Vasoconstriction of the conjunctival blood vessels due to direct
activation of alpha-1 receptors. It is an adrenergic agonist.
o Uses
 Treatment of conjunctival hyperemia.
 0.12% concentration used for vasoconstriction. Chronic use causes
rebound hyperemia, resulting in conjunctivitis medicamentosa,
therefore not a decongestant of choice.
 2.5 and 10% solutions available for pupillary dilation.
 This is generally not the best choice. It has shorter duration and
increased rebound redness.
 It is good for those with a ptosis.
o Dosage
 Topical
 bid-qid
o Adverse effects
 Pupillary dilation, rebound conjunctival congestion with chronic
use, stinging due to pH difference, and upper lid retraction.
o Contraindications
 Cardiovascular disease, hyperthyroidism, DM, and ACG
Imidazole Derivatives
o Increase alpha receptor activity much more than beta receptors activity.
Act as CNS depressors. Increase the effects of tricyclic antidepressants
and decrease the effects of anticholinesterases. Effects of these
vasoconstrictors are potentiated with the use of anticholinergics and



antihistamines, and the effects are decreased with the use of
anticholinesterases. Upon instillation into the conjunctival fornice, these
agents cause vessel constriction due to alpha adrenergic stimulation. Less
rebound congestion and pupillary dilation. Potential for conjunctival
hyperemia exists. Usually combined with other agents.
Naphazoline (Naphcon)
o Mechanism of action
 Vasoconstriction due to activation of alpha-1 receptors. Studies
have shown that this agent is effective in constricting superficial
conjunctival vessels, with no effect on accommodation.
o Clinical use
 Ocular decongestant. Treatment of conjunctival hyperemia.
o Dispensing information
 0.02, 0.05, 0.1, and 0.12% solution
 0.012%- ClearEye, Naphcon
 0.2%- VasoClear
 0.3%- Comfort
 1%
o Adverse Effects
 Ocular- pupil mydriasis up to 3mm, mild elevation of IOP. Slight
tendency to cause rebound conjunctival congestion.
 Systemic- possible HA, HTN, nervousness, nausea
o Contraindications
 Same as phenylephrine, but due to low concentrations, the risk of
toxicity is minimal. Contraindicated in patients taking MAOIs,
ACG, or potentially occludable angles.
Tetrahydrozoline (Murine Plus, Visine)
o Similar to naphazoline. Effective constrictor of superficial conjunctival
vessels. Blanching occurs in 45 seconds and lasts up to 4 hours
o Clinical use- Ocular decongestant
o Toxicity
 Ocular- mild transient stinging, no effect on pupil size or IOP,
although it may cause a transient decrease in IOP.
 Systemic- Same as naphazoline
o Dispensing information
 0.05% OTC
Oxymetazoline (OcuClear, Visine LR)
o Similar to naphazoline. Effective constrictor of superficial conjunctival
vessels. Blanching occurs in 5 minutes with duration of 6 hours.
o Clinical use- Ocular decongestant
o Toxicity
 Ocular- no effect on pupil size, accommodation, or IOP
 Systemic- none reported.
o Dispensing information
 0.025% solution
o Contraindications- Same as naphazoline

Pseudoephedrine
o Most commonly used. Stimulates alpha adrenergic receptors. Promotes
nasal and sinus drainage.
o ADRs
 Possible CV and CNS effects, e.g. HA, insomnia, and nervousness.
Antihistamines




Histamine
o Receptors
 H1: Bronchoconstriction
 H2: Gastric secretion and cutaneous vasodilation, especially local
reactions
 H3: Inhibition of neurotransmitters in the CNS
o Stored by and released from mast cells, basophils, and CNS neurons
o Actions
 Vasodilation
 Triple response (local effect due to H2)
 Localized reddening, localized edema, and flare (redness
that radiates out)
 Bronchoconstriction- due to H1
 Heart- both H1 and H2
 Increased rate (H2)
 Increased contractile force (H1 & H2)
 Pain and itching- H1 activation
 Gastric acid secretion- H2
Actions antagonistic to those of histamine
o Blockade of smooth muscle stimulation (H1)
o Blockade of vasodilation
o Blockade of the triple response
o Diminution of pain and itching
o Does not decrease asthma, because other things (leukotrienes) are
involved with this. Need a B2 agonist
Other actions
o Decreased nausea (so used to treat motion sickness)
o Atropinic effect on secretions
 Decreased salivation, tears, urine, etc.
o Antiparksonian actions
o Antitussive effect- suppresses coughing
o Local anesthetic
o First generation only: CNS depression
Therapeutic uses
o Treat/prevent allergic reactions
o Treat motion sickness
o Treat parkinson’s disease
o First generation only: treat insomnia
Topical Antihistamines






Mechanism of action
o Antihistamines can reversibly block histamine receptors on cell
membranes of the ocular tissue. The receptors are labeled H1 (ocular), H2
(stomach), and H3. They may also prevent release of histamine from mast
cells, basophils, and eosinophils. This means that it is dual action.
o Inhibits tissue edema, itching, and flare by reducing capillary
permeability. Produces localized antimuscarinic, anesthetic, and CNS
effects.
Dosage
o Although these drugs may be used alone, they are commercially available
with a vasoconstrictor to enhance the effects of both medications. Usually
combined with naphazoline or phenylephrine.
o Typical dosage is 1gt every 3-4 hours.
Indications
o Mild to moderate allergic conjunctivitis
o Lid myokymia
o Histamine induced miosis during cataract surgery
Contraindications
o Hypersensitivity to the components
o Narrow angles
o MAOI- can cause hypertensive crisis
o Very young children- can cause CNS depression
o Relativly contraindicated in patients with brittle diabetes and elderly
patients with severe cardiovascular disease or cardiac arrythmias
o Systemic and topical coadministration should be avoided.
Side effects
o Ocular- Mydriasis, decreased vision, anisocoria, allergic reactions,
reactive hyperemia, lacrimation, irritation, pain, burning, stinging upon
instillation, photophobia, decreased IOP, and conjunctival
vasoconstriction.
 Chronic use may cause a rare drug-induced allergy.
o Systemic (rare)- Nausea, sedation, HA, HTN, arrhythmia, hyperglycemia,
nervousness, hypothermia, and anaphylactic reaction.
Formulations
o OTC Antihistamine Formulations (1st Generation)
 Used qid
 Antihistamine (Antazoline phosphate or Pheniramine maleate)
combined with the vasoconstrictor Naphazoline HCl.
 Pyrilamine
 Uses- Seasonal and atopic conjunctivitis
 Preparations
o Prefrin-A
 Phenylephrine HCl 0.12% + Pyrilamine
Maleate 0.1%
 Adverse effects- Transient stinging.
 Pheniramine
 Uses- Seasonal and atopic conjunctivitis
 Preparations
o Naphcon-A (Ocuhist)
 Naphazoline HCl 0.025% + Pheniramine
Maleate 0.3%
o Opcon-A
 Naphazoline HCl 0.027% + Pheniramine
Maleate 0.315%
o AK-Con-A
 Naphazoline HCl 0.025% + Pheniramine
Maleate 0.3%
 Antazoline
 Uses- Seasonal and atopic conjunctivitis
 May decrease IOP slightly.
 Preparations
o Vasocon-A (Albalon-A)
 Naphazoline HCl 0.05% + Antazoline
Phosphate -.5%
 Adverse effect- Transient stinging
o Single-entity Antihistamine (2nd Generation) Rx’d
 Levocabastine (Livostin)
 Drug of choice for acute allergic conjunctivitis. It could
also be used off-label for VKC.
 A powerful H1 blocker. It is potent and rapid.
 Dosage
o 0.05% Suspension, so shake.
o Effective in 15 minutes, duration of 4-6h.
o 1gt qid for up to 2 weeks. Often qid for 1 week and
decrease to bid-tid 2nd week.
 Side effects
o Stinging and burning, Has, visual disturbances, dry
mouth, but usually no CNS effects from topical
instillation.
o Only use for kids over 12 years.
 Emadastine (Emadine)- 0.05% solution, qid
 Solution.
 Used for allergic conjunctivitis
 Same effect with less stinging.
 Dosage qid-bid
 Used in peds greater than 3 years.
 Inexpensive.
o Single-entity, Dual Action Antihistamine





Acts on both H1 and H2 receptors, while also preventing mast cell
degranulation.
Olopatadine Hydrochloride (Patanol)
 Mechanism of action
o A relatively selective H1 receptor antagonist and
inhibitor of histamine release from the mast cell.
 Use
o For the temporary prevention of itching of the eye
due to allergic conjunctivitis.
o Very expensive
 For use of peds greater than 3 years.
 Dosage
o 0.1% solution, bid
o 1-2gtt in each affected eye 2x/day at an interval of
6-8 hours
 Side effects
o Burning, stinging, HA, taste perversion.
Ketotifen fumerate (Zaditor)
 0.25% solution, q8-12h (bid)
 Peds greater than 3 years
 Used for allergic conjunctivitis
 Side effects
o HA, stinging.
 Cheaper
Azalastine (Optivar)
 Bid, 0.05% solution
 Rapid onset (3 minutes)
 Best for itching because it inhibits leukotrienes and PAF.
 Blocks H1>H2.
 For peds 2 and older.
 Side effects
o Bitter taste, stinging, HA
Epinastine
Oral Antihistamines

H1 Antihistamines- Pharmacological Actions
o In addition to blocking the action of histamine and the receptors, these
also exhibit anti-muscarinic, local anesthetic, and CNS effects.
Fexofenadine and loratadine also inhibit histamine release.
o Histamine induces capillary dilation, increase in capillary permeability
(edema), and the clinical signs of pain, itching, redness, tearing can be
alleviated.
o Some have a “dual action” meaning that they both decrease the release of
histamine and eosinophil chemotaxis.


o For Type I allergic reactions, can be useful for symptomatic relief of
allergen induced urticaria, mucosal congestion.
o Non-sedating agents do not penetrate CNS.
General uses
o Allergies (sinusitis, rhinitis)
o Allergen-induced mucosal congestion
o Allergic conjunctivitis: Moderate to severe lid edema (angioedema),
chemosis, itching, tearing where the symptoms are due to Type I
responses.
o Lid myokymia
o Anticholinergic effects
o Insomnia (diphenhydramine and promethazine)
Oral H1 Antihistamines in Current Use
o 1st Generation Antihistamines: Mildly Sedating
 Most OTC
Drug
Dosage
AntiAnti-emetic
Cholinergic
Pyrilamine (Nisaval) 25-50mg
Mild
None
tid, qid
Brompheniramine
4mg, 4Moderate
None
(Dimetane)
6x/day
Chlorpheniramine
4mg
Moderate
None
(Chlor-Trimeton)
q4-6h
Dexchlorpheniramine 2mg, qid- Moderate
None
(Polarmine)
q4h
Triprolidine (Actidil) 2.5mg,
Moderate
None
qid-q4h
Cyproheptadine
4mg, tid
Moderate
None
(Periactin)
 Atarax (Hydroxyzine hydrochloride
 For allergies and dermatitis
 Also good for antianxiety, sedative, and antiemetic.
o 1st Generation Antihistamines: Moderately Sedating
Clemastin (Tavist)
1.34Strong
Strong
2.68mg,
q4-6h
Carbinoxamine
4-8mg,
Strong
Strong
(Clistin)
tid-qid
Tripelennamine
25-50mg, Mild
None
(PBZ)
qid-q4h
Azatadine (Optimine) 1-2mg,
Moderate
None
bid
 Tripelennamine (Pelamine, PBZ)
 Cyclizine (Marezine)
o 1st Generation Antihistamines: Strongly Sedating
Diphenhydramine
25-50mg, Strong
Strong
(Benadryl)
Promethazine
(Phenergan)

tid-qid
12.5Strong
Very strong.
25mg, qdqid
 Benadryl is related to Dramamine (Dimenhydrinate). It is a
derivative.
 Mesarine-Cyclizine, Antivert-Meclizine
 OTC
 For motion sickness and inner ear problems
 Causes drowsiness
o 2nd Generation Antihistamines
 Most are prescribed by doctors. There cannot be purchased OTC.
 Nonsedating, no cholinergic-blocking or antiemetic properties. No
CNS effects. Non-drowsy
 Uses- Mild to moderate allergic rhinitis and conjunctivitis.
Urticaria.
 Longer duration of action
 Better on an empty stomach
 Effects 1-3 hours
 Syrup available for peds
 Dosage- QD
 Contraindications: HTN
Loratidine (Claritin)
10mg, qd Mild
None
Cetirazine (Zyrtec)
10mg, qd Mild
None
Fexofenadine
60mg, bid Mild
None
(Allegra)
180mg, qd
 Allegra-D- added decongestant (pseudoephedrine).
 Astemizole (Hismanal)
 Terfenadine
o 3rd Generation Antihistamines: Non-sedating
Desloratidine
5mg, qd
Mild
None
(Clarinex)
 This is a metabolite of Claritin. It has faster onset and is a better
decongestant, with minimal side effects. There is a low potential
for drug-drug interactions.
Adverse effects
o Sedating antihistamines
 Sedation, depression can vary with dosage and antihistamine used.
Additive CNS effects with various drugs. Also possible CV and
ocular effects. (First generation only).
o Palpations
o Cholinergic blockade- Dry secretions (decreased tears and mucous).
o GI/UT disturbance. Urinary retention.
o Thrombocytopenia
o Allergic pneumonitis.
o Mydriasis (anisocoria)

o Dry eyes and ACG
o Decreased accommodation and visual acuity. Blurred vision.
o Death
Contraindications
o Allergy to antihistamines
o First or third trimester of pregnancy
o Lactation
o Erythromycin, ketoconazole, and itraconazole use
o Other CNS depressants (ethanol, opiods, etc)
o Narrow angles.
o Taking other sedating drugs, including alcohol.
Mast Cell Stabilizers


Mechanism of action
o Acts by stabilizing and inhibiting mast cell degranulation, causing less
histamine, prostaglandin, eosinophils, and platelet aggragation factor. Also
inhibits eosinophil, neutrophil, and monocyte activation. In addition,
TBUT is prolonged. Does not appear to accumulate in CL.
o Slower onset, so use only with chronic allergies.
Types
o Cromolyn Sodium (Crolom)
 This prevents calcium influx.
 Clinical Use
 Allergic conjunctivitis, vernal conjunctivitis (VKC), GPC
(off-label), oculodermatologic disease
 Dosage
 4% topical solution
 Used 4-6x/day. Symptomatic relief takes several days to
several weeks. This has the longest onset (7-14 days).
 Preserved with BAK and EDTA. Shelf-life of 36 months.
Should be discarded 4 weeks after opening.
 Adverse effects
 Ocular: transient ocular stinging, conjunctival injection,
watery or itchy eyes, styes, dryness around the eyes. May
prolong TBUT.
 Contraindications
 Hypersensitivity to BAK
 Not for use in kids les than 4 years.
o Lodoxamide Tromethamine (Alomide)
 Mechanism of action
 Like Crolom, but 2500x more potent.
 It also plays a role in inhibition of eosinophil migration and
decreased leukotrienes.
 Clinical Use

Only FDA approved at first for vernal keratitis and
conjunctivitis, but already enjoys widespread use for a
variety of allergic disorders, such as VKC and GPC.

Dosage
 0.1% solution
 1-2gtt qid for up to 3 months.
 Contraindication- Do not use in kids less than 2 years.
o Nedocromil Sodium (Alocril, Tilavist)
 Background
 Tilavist is not available in the US.
 It is the best mast cell stabilizer for itching, and has the
fastest onset (15 minutes).
 It has a slightly yellow color and an unpleasant taste.
 Mechanism of action
 More potent than cromolyn. It modifies the actions of
eosinophils, neutrophils, monocytes, macrophages, and
platelets.
 Clinical Use
 Approved for seasonal allergic conjunctivitis.
 Dosage
 2% solution
 Bid to tid
 Contraindications
 Do not use in kids less than 3 years
 Pregnancy category B
o Permirolast (Alamast)
 Clinical Use- Approved for seasonal allergic conjunctivitis. This is
the best mast cell stabilizer for chronic use. It is the best for
itching.
 Dosing
 0.1% solution
 Dosage is qid. Onset is immediate.
 Adverse effects
 Transient burning and stinging, ocular discomfort,
conjunctival injection, watery/itchy eyes, dryness around
the eyes, puffy eyes.
 HA, unpleasant taste sensation, nasal congestion.
 Contraindications
 Don’t use in kids less than 3 years.
 Sensitivity to any components.
Pain Relievers/ Analgesics
Pain Perception and Transfer
 Mechanisms of pain perception

o Pain is an unpleasant sensory, emotional experience associated with actual
or potential tissue damage. Nociceptors are specialized nerve endings.
They are activated by trauma and chemical mediators (i.e. bradykinin, 5HT) in response to injury, transmitting pain either via mechanical
stimulation or chemical stimulation with acetylcholine, serotonin,
bradykinin, or histamine. These are all autocoids that are related to pain
sensation. Pain signals are conveyed from the stimulated nociceptors to
the CNS. The impulse is conveyed to the brainstem, to the sensory and
spinal nuclei of the trigeminal nerve, to the thalamic nuclei (where pain is
perceived), and then to the somatosensory cortex (where pain is localized).
o Prostaglandins (PGE2, PGI2) accentuate pain-producing effect of noxious
stimuli. These interact with pain mediators.
Physiological Manifestations of Pain
o Tachycardia, systemic HTN, tachypnea, increases risk in patients with
COVD, emotional distress because of poor sleep and anxiety.
Nonopioid Analgesics (Non-narcotics)
 Peripherally acting. None of these are strong, but they are very toxic.
 Salicylates
o Aspirin (acetylsalicylic acid, ASA)
 This comes from the bark of the willow tree and is the least
expensive
o Mechanism of action
 Aceylates cyclooxygenase enzyme, thereby inactivating it and
inhibiting prostaglandin E2 synthesis. It may also suppress the
perception of pain by hypothalamic actions.
o Clinical uses
 This is a low-dose analgesic used for mild to moderate acute and
chronic pain or headaches. This can be used chronically. Adverse
effects may limit use.
 Inhibits pain and inflammation. It may also lower fevers
(antipyretic).
o Dosing
 Available as tablet, enteric-coated tablet, controlled release tablet,
and suppository. Also in combination with opioids.
 Adult dosage is 325-650mg q4-6h. max: 4000mg.
 More anti-inflammatory with increased dosage (3-4g qd)
 Single treatment dose inhibits platelet function for 8-10 days.
o Commonly used aspirin products
Aspirin (Generic)
Tablet
325mg
Genuine Bayer
Tablet
325mg
Empirin
Tablet
325mg
Maximum Bayer
Tablet
500mg
Ecotrin
Enteric-coated tablet
325mg
Ecotrin Maximum Strength
Enteric-coated tablet
500mg
8h Bayer Timed Release
Timed-release tablet
650mg
Aspirin (Generic)

Suppository
120,
200,
300,
600mg
325mg
325mg
325mg
500mg
Buffed Aspirin (Generic)
Buffered tablet
Ascriptin/ VD
Coated, buffered tablet
Bufferin
Coated, buffered tablet
Ascriptin Extra Strength
Coated, buffered tablet
o Side effects
 GI disturbances (less if taken with meals). This is due to the fact
that it is a nonselective inhibitor. COX-1 is associated with GI and
renal protection. COX-2 is associated with inflammation and
injury. Aspirin interferes with both of these. If using chronically,
avoid using nonacetylated salicylates, H2 blockers, or misoprostol
(Cytotec).
 Bleeding due to decreased platelet aggregation.
 CNS effects (Tinnitis, Headache, Dizziness)
 Hypersensitivity (Type I)
 Drug interactions
 Reye’s Syndrome in young patients with a systemic viral infection.
This is vomiting, hepatic disease, and encephalopathy.
 Local tissue damage if the tablet lodges in the esophagus.
 Hyperthermia with an overdose due to an uncoupling of oxidative
phosphorylation. This means that there is a decrease in ATP and
extra energy is put off as heat.
 These effects are decreased with coated and controlled tablets.
There is decerased GI upset, but decreased onset. Good for chronic
use.
 Take with food and full (6-8oz) water.
 Acute overdose is indicated by tinnitus, hearing loss, dizziness,
fever, vomiting, and coma.
 Chronic overdose is indicated by GI irritation, ulcers, and
hemorrhage.
o Contraindications
 Upper GI disease
 History of asthma, nasal polyps, or aspirin allergy
 Bleeding disorders (hyphema) or anticoagulant therapy
 Post cataract or other invasive surgery
 Chronic renal or hepatic disease
 Pregnancy, especially 3rd trimester- category D
 No kids with viral infections (influenze or chickn pox) Reyes
Syndrome, causing swelling of brain, unconsciousness, liver
damage, etc.
Nonacetylated Salicylates
o Lower incidence of GI effects and less effect on platelet aggregation (does
not increase bleeding). There is no cross reactivity with aspirin.
o Agents
Disalcid
Sodium Salicylate
(Generic)
Arthropan

Salsalate
- Hydrolyzed to
salicylic acid.
Sodium Salicylate
500mg capsules
500-750mg tablets.
325-650mg entericcoated tablets
870mg/5ml liquid
Choline Salicylate
- Most frequently
used.
Original Doan’s
Magnesium
325 mg caplet
Salicylate
Extra Strength
Magnesium
500mg caplet
Doan’s
Salicylate
- No antipyretic
- Converted to
effects.
salicylic acid.
Trilisate
Choline-Magnesium 500, 750, 100mg tablet
Salicylate
500mg/5ml liquid.
Acetaminophen (APAP, Tylenol, etc)
o Mechanism- Inhibition of prostaglandin synthesis
o Effects
 Relief of mild to moderate pain, fever (antipyretic), but there are
no (very little) inflammatory properties. Analgesic effect is
comparable to ASA except in inflammatory conditions.
 Does not inhibit platelet aggregation or affect prothrombin time.
This means decreased GI upset and no cross sensitivities with
NSAIDs. There is no Reyes syndrome.
 Metabolized in liver. Kidney excretion.
 Limit dose to 2,000mg/day with warfarin and coumadin.
o Clinical Uses
 Headache, fever, and other types of mild pain.
 When NSAID therapy is contraindicated, i.e. allergy to ASA or
other NSAIDs; upper GI disease; bleeding disorders or following
cataract extraction; children and adolescents; pregnancy and
lactation.
 Can alternate doses with ibuprofen.
o Adverse effects
 Hepatic necrosis
 Due to loss of glutathione (GSH). This is seen more in
chronic alcoholics with pre-existing liver damage.
Therefore, do not use this to treat hangovers.
 Seen with doses greater than 10-15 grams.
 Treat with acetylcysteine- used to treat asthma
 Renal damage
Acetaminophen Unisert
Suppository
120, 325, 650
Children’s Tylenol
Chewable Tablet
80
Junior Strength Tylenol
Elixir, Tablet
160/5ml, 160
Tylenol Regular Strength
Tylenol Extended Relief
Anacin-3
Acetaminophen -Generic
Tempra Syrup
Acetaminophen DropsGeneric
Bromo Seltzer


Tablet
Dual-layer Caplet
Tablet
Tablet
Liquid
Solution
325
650
325
325, 500, 650
160/5ml
100/ml
Buffered
325
effervescent
granules
Nonopioid Combination Formulations
o APAP, salicylates, salsalate, or salicylamide
o Barbiturates, meprobamate, or antihistamines
o Antacids
o Caffeine
Trigesic Tablets
Acetaminophen (125)
Aspirin (230)
Caffeine (30)
Vanquish Caplets
Acetaminophen (19.1)
Aspirin (227)
Caffeine (33)
Buffers
Excedrin Caplets and Tablets Acetaminophen (250)
Aspirin (250)
Caffeine (65)
Excedrin PM Tablets
Acetaminophen (500)
Diphenhydramine (38)
Anacin Caplets and Tablets
Aspirin (400)
Caffeine (32)
Anacin Maximum Strength
Aspirin (500)
Tablets
Caffeine (32)
Propionic Acid Derivatives.
o Mechanism- Inhibition of prostaglandin synthesis
o Effects
 Relief of mild to moderate pain
 Relief of fever
 Relief of inflammation
o Therapeutic uses
 Headache, fever, and other painful disorders.
o Types
Classification Trade
Generic
Formulation Adult
Antiinflammatory
Name
Name
Analgesic Dose
Dose
Propionic
Motrin,
Ibuprofen
200, 300,
200-400
400-600mg
Acid
Advil,
400, 600,
q4-6h
Nuprim
Naprosyn
Naproxen
(Plasma
protein
binding,
therefore
increased
duration
of action.)
Anaprox,
Aleve
Naproxen
sodium
Nalfon
Fenoprofen
Orudis
Indoleacetic
Acids
Indocin
Toradol
Anthranilic
Ponstel
800mg
tablets.
100mg/5ml
suspension
250, 375,
500mg
tablets.
125mg/5ml
suspension.
375, 500mg
entericcoated
delayed
release
tablet.
OTC220mg
tablets
220, 275,
550mg
tablets
200, 300mg
capsules;
600mg
tablets
Ketoprofen
25, 50,
75mg
capsules.
OTC12.5mg (1-2
q4-6h)
Indomethacin 25, 50mg
capsules;
* Mild anti75mg
inflammatory sustainedeffects. Best
release
for those
capsule;
with kidney
25mg/5ml
disease.
suspension
Ketorolac
10mg tablet
tromethamine (Also in IV)
Mefenamic
250mg
Acid
capsule
MDD
OTC-2400
Rx- 3200
500mg
initial
dose,
followed
by 250
q8h.
375mg bid
MDD
OTC- 660
Rx- 1000
550
initial
dose
followed
by 275
q6-8h
200 q46h
25-50 q68h. 2575mg
25 q812h
10 q4-6h
500
initial
75mg
MDD
OTC- 75
Rx-300
dose
followed
by 250
q6h
Sulindac



Clinoril
* Good for
those with
damaged
kidneys and
elderly. It is a
prodrug.
o Adverse effects
 Hepatic damage, renal damage, confusion, transient inhibition of
platelet function, and mild GI upset
Acetic Acid Derivatives
o Agents
 Indomethacin (Indocin)
 Sulindac (Clinoril)- metabolized to sulfide (active form)
 Tolmetin (Tolectin)
o Uses
 Relieves inflammation, pain, and fever.
 Patent ductus arteriosus
 Fetus’ blood not oxygenated from the lungs (from
placenta). With birth, you want to change this. But if it
doesn’t, baby turns blue. Indomethacin closes this.
o Adverse effects
 Hepatic and renal damage
Phenylbutazone (Butazolidin)
o Relieves pain, inflammation, and fever
o Adverse effects
 Leucopenia, agranulocytosis, aplastic anemia, hepatic damage, and
renal damage.
Colchicine
o Stops cell division in metaphase
o Primary anti-inflammatory, but also used for gout.
Nonsteroidal Antiinflammatory Drugs (NSAIDs)
 Mechanism
o Inhibits synthesis of prostaglandins, via inhibiting COX. Therefore it
relieves pain. It does not inhibit leukotriene synthesis. One would need to
use a corticosteroid for this.
 Uses
o Prevent intraoperative miosis (main use)
o Manage postsurgical and nonsurgical inflammation
o Prevent or treat CME after cataract extraction
o Control ocular pain after corneal abrasions or RK

o Control post-PRK myopic regression.
o Mild to moderate pain
Types
o Salicylates
 Agents
 Aspirin and Salsalate (Disalcid)
 Diflunisal (Dolobid): For patients intolerant of aspirin.
 Mechanisms
 Inhibition of cyclooxygenase-1 (COX-1; found in stomach,
vessels, and kidneys)
 Inhibition of cyclooxygenase-2 (COX-2; found in
inflammatory cells)
 Clinical uses
 Relief of pain and inflammation.
 Rheumatoid arthritis, Osteoarthritis, and Ankylosing
spondylitis
 Adverse effects- Same as non-opioid analgesics
o Propionic Acid Derivatives
 Agents (non-selective)
 Ibuprofen (Motrin, Advil, Nuprin)
o Mechanism of action
 Propionic acid derivative which acts to
inhibit prostaglandin synthesis. Is an NSAID
with anti-inflammatory, anti-pyretic, and
analgesic properties.
 Better tolerance than aspirin with most
patients. Also has less gastric irritation and
bleeding than aspirin. Reduces the diuretic
effects of Furosemide (Lasix) and the effects
of anti-hypertensives.
o Dosage
 200-800mg tablets
 Typical dosage: 300-600mg tid or qid
o Indications
 RA, osteoarthritis, primary dysmenorrheal,
decreased fever, and mild to moderate pain.
o Contraindications
 Upper GI disease, HTN, impaired renal
failure, coagulation defects, and anticoagulant therapy.
o Side effects
 Ocular: transient blurred vision, diplopia,
myopia, changes in color vision, dry eye,
and photophobia.
 Systemic: N, V, ulcers, flatulence, diarrhea,
constipation, pruritis, urticaria, erythema
multiforme, Steven-Johnson, dizziness, HA,
depression, insomnia, CHF, HTN,
palpitations, neutropenia, agranulocytosis,
anemia, eosinophilia, tinnitus, and decreased
appetite.
 Fenoprofen (Nalfon)
 Flurbiprofen (Ansaid)
 Naproxen (Naprosyn, Aleve)- longer lasting (1x/day)
 Oxaprozin (Daypro)
 Mechanism- Inhibition of COX-1 and COX-2
 Therapeutic uses
 Relief of inflammation and related pain.
 Rheumatoid arthritis, Osteoarthritis, Ankylosing
spondylitis, and Gout
 Adverse effects
 Hepatic and renal damage
 Naproxen dosage limited to one tablet per day (can damage
liver)
o Acetic Acid Derivatives
 Agents
 Indomethacin (Indocin), Suldinac (Clinoril), and Tolmetin
(Tolectin)
 Mechanisms
 Inhibition of COX-1 and COX-2
 Inhibition of leukocyte migration (decreased inflammation)
 Uses
 Relieves inflammation, pain, and fever.
 Acute gouty arthritis, Ankylosing spondylitis,
Osteoarthritis, and Psoriatic arthritis.
 Adverse effects
 Hepatic and renal damage, as well as headaches
(Indomethacin).
o Nonselective (COX-1 and COX-2 inhibitors)
 I.e. ibuprofen, naproxen, and ketoprofen
 GI effects- Inhibit platelet aggregation (only with active drug in the
blood). May also have CNS, kidney, and liver effects.
o Selective COX-2 Inhibitors- anti-inflammatory and analgesic.
 This has less GI effect. Do not inhibit platelet aggregation.
Decreased renal blood flow/fluid retention.
 Don’t use with nonselectives.
 Use in kids greater than 18 years.
 COX-1- in most cells (especially GI mucosa)- Good
 COX-2- increases with inflammation- Bad. Increased
prostaglandins in eyes and tissues.
 Celecoxib (Celebrex)- rheumatoid and osteoarthritis

o
o
o
o
o
o
100-200mg q12h. MDD 400. Do not use with sulfa
allergies.
 Refecoxib (Vioxx)- acute pain and osteoarthritis
 50mg qd for pain, 12.5-25 qd for arthritis. MDD 50
 Also available in a 25mg/5mg suspension.
 Valdecoxib (Bextra)- osteoarthritis, RA, dysmenorrheal
 10mg qd-20mg bid.
Nabumetone (Relafen)
 Analgesic, antipyretic, and anti-inflammatory
 Mechanism: inhibition of COX-1 and COX-2
 Less gastric irritation than other NSAIDs.
Phenylbutazone (Butazolidin)
 Relieves pain, inflammation, and fever
 Uricosuric- increase urinary output of uric acid.
 Adverse effects
 Leucopenia, Agranulocytosis, Aplastic anemia, Hepatic
damage, Renal damage
 Therapeutic uses
 Acute gout and Rheumatoid arthritis
Gold Compounds
 Crysotherapy is the use of a gold compound.
 Agents
 Auranofin (Ridaura)
 Gold Sodium thiomalate (Myochrisine)
 Probable mechanism- Interference with maturation and function of
mononuclear phagocytes and T cells
 Therapeutic use- Rheumatoid arthritis
 Adverse effects
 Dermatitis (exfoliative, severe), renal damage, and
lenticular deposits
 Metallic golds are not toxic. Only gold salts and other gold
compounds.
Immunosuppressive Antiinflammatory Agents
 Also used to treat cancer
 Azathioprine (Imuran)
 Methotrexate (Folex)
 Cyclophosphamise (Cytoxan)
Antimalarials
 Chloroquine (Aralin)
 Hydroxychloroquine (Plaquenil)
Colchicine
 Therapeutic use: Gout
 Mechanisms
 Blocks mobilization of leukocytes
 Blocks release of inflammatory mediators from
macrophages.
o Probenecid (Benemid)
 Mechanism- Inhibition of uric acid reabsorption in the kidneys,
causing uricosuria.
 Therapeutic use- Chronic gout
o Sulfinpyazone (Anturane)
 Mechanism- Inhibition of uric acid reabsorption in the kidneys,
causing uricosuria
 Therapeutic use- Chronic gout
o Allopurinol (Zyloprim)
 Mechanisms- Interference with xanthine oxidase, thus blocking
uric acid synthesis
 DNA  Hypoxanthine  Xanthine  Uric Acid 
Allopurinol  Alloxanthine  Other metabolites
 Therapeutic uses
 Hyperuricemia (increased uric acid in the blood)
 Gout
Topical Ocular NSAIDs


Background
o No effect on the IOP.
o Dosage varies with clinical indication
o Off label use- CME
Types
o Flurbiprofen (Ocufen)
 Maintains pupillary dilation during cataract surgery
 1gt q30min x4
 Manages postoperative inflammation and prevents CME
 Adverse effect- Transient stinging
o Suprofen (Profenal)
 Preserved with BAK
 Maintain pupillary dilation during cataract surgery
 2gtt 3x before surgery and 2gtt 5x/day after surgery
 Adverse effects
 Transient ocular irritation, but less stinging if formulation
contains 1% caffeine
 Wound healing may be delayed.
o Diclofenac (Voltaren Ophthalmic)
 0.1% solution.
 Preserved with BAK
 Decreases PGE2 and LTB4 production
 Clinical Uses
 Control inflammation following cataract surgery
 Decrease pain and inflammation following PRK
 Prevent intraoperative miosis



FDA approved for prevention of post-cataract
inflammation, photophobia, and corneal pain, not SAC
 Adverse effect
 Transient stinging
 Pregnancy category B
o Ketorolac tromethamine (Acular, Acular PF)
 0.5% solution, qid.
 Preserved with BAK, but also available in Acular PF.
 Inhibits prostaglandin synthesis
 Clinical Uses
 Conjunctival inflammation
 Control inflammation following cataract surgery
 Prevent and treat CME
 Approved for SAC, post-op inflammation, corneal pain,
and photophobia. This is the only drug approved by the
FDA for SAC.
 Adverse effects
 Causes less stinging than other NSAIDs
 Pregnancy category C
Adverse effects
o Minor irritation, stinging, punctate keratitis, and rare allergic reactions
o Seen especially if preserved and generic brands are used
o May delay wound healing
o Ocular irritation, dry eyes, corneal deposits
Contraindications
o Hypersensitivity to aspirin
o Pregnant (last 3 months)
o On blood thinners (gingko, vitamin E, etc) or other bleeding tendencies
o Use of soft contact lenses
Opioid Analgesics



Receptor Types
o Mu
 Mu1- Mediates analgesia in the brain. “Supraspinal”
 Mu2- Mediates analgesia in the spinal cord and respiratory
depression in the brain.
o Kappa- Mediates analgesia in the spinal cord and the brain
o Sigma- Mediates psychomimetic effects. “Euphoria”
o Delta- Mediates analgesic effects of endogenous opioids “Endorphans”
Opiates- Analgesics obtained from the opium poppy (Papaver somniferum) and
derivatives of these
Mechanism of action
o Binds to opioid receptors (μ, δ, and κ) in the brain and act on the central
nervous system. This limits the sensation of pain and reaction to pain
(emotional component).


o If natural, it can cause severe miosis, constipation, histamine release, and
respiratory depression. Synthetics are more likely to cause ADRs.
Clinical Use
o Severe, acute pain.
o Limit the prescription initially (48-72h) and do not refill without
examination. Opioids may be safer if contraindication to NSAIDs and
addictions are rare.
Natural Drugs
o Morphine (MS Contin)- Gold Standard
 Related to heroin and is the prototype opioid.
 Stimulates mu1, mu2, kappa1, and kappa3.
 A scheduled drug, so a DEA number is required to prescribe.
There is a potential for abuse and addiction.
 Actions
 Analgesia
 Peripheral vasodilation
o Blush area (face, ears, neck), warming, sweating,
itching, and scratching
 Nausea, with first dose, due to the stimulation of
chemoreceptor trigger zone and the slow depression of the
vomiting center.
 Constipation due to the increased tone of GI musculature,
decreased GI motility, and increased sphincter tone
 CNS Depression (respiratory depression and drowsiness)
 Miosis, due to increased parasympathetic activity
 Tolerance
o Especially to psychomimetic effects
o Little tolerance to miosis or GI actions
 Uses
 Relief of severe pain
o More pain means more morphine can be tolerated.
 Sedation of patients in pain
 Treatment of acute pulmonary edema
 Relief of cough
o Decreases the cough center in the medulla.
 Treatment of diarrhea.
 Dosing
 Routes of Administration: im, sc, po (need large dose due
to first pass metabolism, via enterocytes in the gut and
liver), intrathecally (injected into the spinal cord to relieve
large areas of the body)
 Oral, slow releasing
 10g more effective and more potent than 325mg of aspirin.
 No “ceiling effect” but ADRs to the CNS limit dosage.


Acute intoxication is indicated by coma, respiratory depression,
and pinpoint pupils, which is only seen with opioids and
insecticides (organophosphates).
o Codeine
 The most prescribed opiod in the US. It is less potent than
morphine, so it is often combined with non-opiod analgesics, such
as aspirin, etc. There is a low potential for addicition. It is such a
mild analgesic, but it also contains good antitussive properties.
 Dosing
 Oral- effective within 20 minutes, maximum in 1-2h,
duration 4-6h.
 Dosage not limited by a ceiling effect, but by a toxic effect.
 Relatively high degree of sedation and GI effects (N, V, dizziness)
o Oxycodone/ Oxycontin
 Oral administration is 20x as potent as codeine. This is a strong
analgesic. It may produce euphoria and is a target of drug abuse.
 Dosing
 Formulated with acetaminophen (Percocet, Tylox) or
aspirin (Percodan) for moderate/severe pain.
 Duration 12 hours.
 Do not chew, because it is sustained release.
 Lower incidence of side effects compared to codeine and
morphine. An overdose leads to respiratory depression
o Hydrocodone (Lortab)
 Oral is 6x more potent as codeine
 Less GI effects and sedation than codeine, but more euphoria.
Death is generally due to respiratory depression.
 Combination with acetaminophen is Vicodin
 Has a potentiation effect
o Hydromorphone (Dilaudid)
 Used as an analgesic for cancer and antitussives.
 5x more potent (10-15mg)
o Oxymorphone (Numorphan)
 Administered orally
 10x potency
Synthetic Agents
o Propoxyphene (Darvon)
 Not a true narcotic. It is an analogue of methadone.
 It is a mild analgesic with sedative properties. It may be less
effective than 600mg ASA, so it could be argued that it is possibly
a placebo. Mostly utilized by dentists. More effective in
combination with ASA or APAP.
 Dosing
 Administered orally
 Available as the hydrochloride or napsylate (better GI
absorption)

 Single entity formulations
 Darvacet is a combination of propoxyphene and acetaminophen.
o Pentazocine (Talwin NX)
 Used more in hospital settings. Analgesic efficacy comparable to
ASA and APAP
 Mixed agonist-antagonist
 Oral. No effect unless taken orally.
 Adverse effects include confusion and hallucinations, along with
dysphoria (10%). There is less respiratory depression than with
opioid agonists.
 Can precipitate withdrawal in patients taking opioid agonists
 The NX is naloxone, which is used to prevent abuse.
 NX = Talwin + Naltrexone
o Tramadol (Ultram)
 Nonopioid working on opioid receptors- nonaddictive
 For moderate to severe pain
 50-100mg q4-6h
 Taken without regard to meals
 Don’t use with history of seizures
 Ultracet = tramadol + APAP
Synthetic Opioids
o Meperidine (Demerol)
 Given by any route.
 Shorter duration of action than morphine (1/10x potency)
 No miosis
 Not antitussive
 OD is indicated by respiratory depression, coma, (no pinpoint
pupils)
o Fentanyl (Sublimaze)
 100x as potent as morphine (use a very small dose)
 Large dose can cause rigid respiratory paralysis (due to lead pipe
rigidity. Cannot even do CPR without a muscle relaxant).
 Routes of administration
 IV (Sublimaze)
 Transdermal (Duragesic patch)
 Transmucosal (Fentanyl Oralet) “Hard candy”
o Buprenorphine (Temgesic)- A partial agonist of mu receptors, therefore
decreased respiratory depression.
o Butorphanol (Stadol) and Nalbuphine (Nubain)
 Oral
 Decreased respiratory depression
o Levorphanol (Levo-Dromoran)- Administered orally
o Methadone (Dolophine)- Used in addicts as a substitute for other opioids.
This causes dysphoria, the opposite of euphoria. It is then gradually
withdrawn.
o Nalorphine
 Significant dysphoria and is not used as an analgesic.
o Sufentanyl (Sufenta)- Strong analgesic
o Alfentanil (Alfenta)
o Etorphine- Very potent. Good to tranquilize large animals.
 Side Effects
o Dosage is limited by toxicity.
o CNS- Drowsiness and euphoria. Dizziness. CNS depression, including
respiratory depression.
o GI- Constipation, N, V
o Palpitations, bradycardia, and hypotension
o Respiratory depression.
o Miosis
o Take on full stomach, avoid alcohol and all CNS depressants and use
caution when driving.
 Contraindications
o Hypersensitivity to opioids
o Acute bronchial asthma and COPD
o Renal or hepatic dysfunction
o Abuse potential
o Pregnancy and lactation
 Management of ADRs
o Prescribe laxatives along with opioid
o Treat nausea by limiting physical activity
o If NSAIDs are sufficient, but GI irritation, prescribe enteric-coated
formulations.
o Treat toxicity with naloxone (Narcan).
 Analgesic Use in Substance Abusers
o Deficient drug metabolism and drug absorption
o Tolerance to opioids
o Potential for withdrawal symptoms.
Opioid
Trade Name
Formulations
Federal
Adult
Controlled Dosage
Substance
Schedule
Codeine
Tylenol with
Codeine (30)
C-III
1-2 q4h
Codeine no.3
Acetaminophen (300)
tablets
Tylenol with
Codeine (60)
C-III
1 q4-6h
Codeine no. 4
Acetaminophen (300)
tablets
Empirin with
Codeine (30)
C-III
1-2 q4h
Codeine no. 3
Aspirin (325)
tablets
Acetaminophen
Codeine (12)
C-V
12ml q4h
with codeine elixir Acetaminophen (120)
(Generic)
Oxycodone
Percocet Tablets
Tylox Capsules
Percodan Tablets
Hydrocodone
Propoxyphene
Pentazocine
Lortab Liquid
Oxycodone (5)
Acetaminophen (325)
Oxycodone (5)
Acetaminophen (500)
Oxycodone HCl (4.5)
Oxycodone
terephthalate (0.38)
Aspirin (325)
Hydrocodone (2.5)
Acetaminophen (120)
Hydrocodone (5)
Acetaminophen (500)
Lortab 5/500
Tablets
(Vicodin, Anexsia)
Darvon Capsules
Propoxyphene HCl
(65)
Darvon-N Tablets Propoxyphene
napsylate (100)
Darvocet-N 100
Propoxyphene
Tablets
napsylate (100)
Acetaminophen (650)
Talwin NX Tablets Pentazocine (50)
Naloxone (0.5)
Talacen Capsules
Pentazocine (25)
Acetaminphen (650)
C-II
1 q6h
C-II
1 q6h
C-III
1 q6h
C-III
5ml q4h
C-III
1-2 q4-6h
C-IV
1 q4h
C-IV
1 q4h
C-IV
1 q4h
C-IV
1-2 q3-4h
C-IV
1 q4h
Acetominophen-Codeine (Tylenol 3)
 Mechanism of action
o Acetaminophen is an NSAID agent which possesses analgesic and antipyretic properties of aspirin. It is a weak inhibitor of prostaglandin
synthesis. However, it does not induce gastric ulceration, inhibit clotting,
and has less anti-inflammatory properties than aspirin. Acts directly on the
hypothalamus. Codeine is an opium alkaloid and possesses properties
similar to morphine. It affects the CNS for its analgesic properties.
 Dosage
o Tablets, capsules, elixir- various combinations
o 1-2 tablets q4h
o Onset: 15-30 minutes, Peak: 30-60 minutes, Duration: 4-6 hours.
 Indications
o Moderate to severe pain
 Contraindications
o Caution with the elderly
o Severe renal disease
o Severe liver disease
o Head injuries
o Hypothyroidism
o Addison’s disease



o Prostatic hypertrophy
o Urethral stricture
Side effects
o Sedation, lightheadedness, euphoria, dysphoria, nausea, emesis,
constipation, pruritis, shortness of breath, physical dependence
o Ocular: decreased vision, myopia, mydriasis, and decreased color vision.
Combinations of Opiod and Non-opiod analgesics
o Greater analgesic effects with no increase in adverse effects.
o Caffeine enhances the effectiveness of both categories.
Opioid Antagonists
o Complete antagonists with no agonistic actions.
 Reverses toxic and therapeutic effects
 Naloxone (Narcan)- shorter duration of action than most opioids
 Naltrexone (Trexan)- via injection
o Complete antagonists that are agonistic when given alone
 Nalorphine (Nalline)
 Levallorphan (Lorfan)
o Partial antagonists that are agonists when given alone
 Pentazocine (Talwin)
 Nalbuphine (Nubain)
 Buprenorphine (Temgesic)
 Butorphanol (Stadol)
Mineralocorticoids
 Agents
o Aldosterone
 Synthesized in the adrenal cortex. This acts in distal convoluted
tubule by promoting reabsorption of sodium and excretion of
potassium in the kidney. Water is absorbed with sodium. Secretion
governed by rennin-angiotensin system
o Fludrocortisone (Florinef)
o Desoxycorticosterone acetate
 Uses
o Adrenocortical insufficiency
o Aldosterone insufficiency with diabetes insipidus.
Anti-Edema Drugs
 Corneal Hydration (78% Water)
o Causes of corneal edema
 Endothelial decompensation
 No active transport of water out.
 Increased IOP
 Drives fluid into the cornea.
o Stromal edema results in decreased corneal transparency

o Epithelial edema
 Results in anterior irregular astigmatism
 Responds well to topical hyperosmotic agents.
Topical Hyperosmotic Agents
o Increase tonicity of the tear film.
o Mechanism: osmotic effect on fluid within the cornea. Pulls fluid out.
o Sodium chloride
 5% is optimal (0.9% isotonic with tears/normal saline)
 Preparations
 Solutions- 2-5%; 1-2 gtt q3-4h
 Ointments 5% (decreased edema in 3-4h)
 Much less effective if epithelium is damaged because it goes to the
stroma.
o Glycerin (Glycerol)
 Hygroscopic- absorbs water. Decreased edema in 1-2 min.
 Local anesthetic is necessary prior to instillation (stings).
 50-100% solution.
 Uses: ophthalmic and gonioscopic examination in
 ACG
 Bullous keratopathy
 Fuch’s endothelial dystrophy
o Glucose
 Preparations
 30-50% solutions. Be in contact for 30 minutes and works
in 3-4 hours.
 Ointment preserved with methylparaben and propylparaben
 Adverse effects: transient stinging
Dyes
 Fluorescein
o A yellow acid dye that absorbs certain wavelengths and emits longer
(542nm) wavelengths on the eye.
o Anionic at physiologic pH (7.4), meaning that it does not penetrate the
intact cornea.
o Intensity of fluorescence increases with increasing concentrations (up to
0.001%)
o Intesnsity of fluroescense increases with increasing pH (up to 8)
 pH <2: cationic (fluoresce weak blue green)
 2-4: anionic/cationic (blue green)
 >7: anionic (yellow green)
o Preparations
 Solutions
 Topical
o Fluorescein sodium solutions
o Fluress: contains chlorobutanol and benoxinate
(anesthetic)
o Fluorocaine: contains proparacaine, povidone,
glycerin, and thimerosal.
o Proparacaine fluorescein
o Supports the growth of pseudomonas, so needs
preservatives.
 IV
Filter paper strips
 Ful-Glo
 Fluor-I-Strip
 Fluor-I-Strip-A.T.
 Fluorets
o Remove with irrigating solutions
o Uses
 Topical administration
 Detection of corneal and conjunctival lesions (abrasions,
ulcers, etc)
o Accumulates in the defect
o Fluoresces; does not stain
 Fitting and management of rigid, GPCL
 Evaluation of the lacrimal system
o TBUT
o Epiphora
 GAT
 IV administration
 Angiography: detection of neovascularization, macular
lesions, CSC, DR, disciform macular degeneration,
papilledema, malignant melanomas, metastatic tumors,
hemangiomas of the choroid.
 Circulation time
 Iris angiography: detection of tumors and vessel infarcts.
 Measurement of aqueous flow rate
 Vitreous fluorophotometry
 Oral administration
 1-2g in chilled cirus juice
 detect macular leakage
 CME
 Retinal vascular abnormalities
o Adverse effects
 Generally seen with IV administration
 Nausea in 15-30 sec
 Allergic reaction
 Discoloration of skin and of urine
 Topical application: local irritation






Staining of SCL
Fluorexon
o Pale yellow/brown
o Chemical identity: N,N-bis(carboxymethyl)-aminoethylfluorescein
tetrasodium salt
o Stains epithelial defects and devitalized tissue
o Susceptible to bacterial contamination, therefore dispensed in single doses.
o Use: fitting of SCL
o Adverse effects
 Transient staining of SC
 Mild stinging
 Conjunctival injection
o Contraindications: highly hydrated SCL (>60%), because they stain.
Rose Bengal
o Stains living cultured cells, degenerated cells, dead cells, and mucus
strands
o Preparations
 1% solution
 Filter paper strips
o Uses
 Topical applicaton
 Differential diagnosis of DES
 Evaluation of corneal and conjunctival lesions
 Evaluation of dendrites
o Can interfere with viral diagnosis, because it is an
antiviral.
 Evaluation of conjunctival dysplasia and metaplasia
 IV application
 Studies of hepatic function
 Ocular uses: animal studies only.
o Adverse effects
 Stinging
 Some cell destruction
 Stains skin, clothing, and SCL
Lissamine Green
o Preparation: 1% solution
o Similar to rose Bengal; used when a red dye is not desirable or when
another red dye is used simultaneously.
o This also possesses some antiviral properties.
Indocyanine Green
o Use: retinal and choroidal angiography
 Choroidal neovascularization
 Several other choroidal abnormalities
o Administered intravenously
o Adverse effect: allergic reaction
o Contraindications


 Iodine sensitivity
 High risk of anaphylactic reaction
Trypan Blue
o Stains dead or damages endothelial cells
o Uses
 Determine suitability of corneal material for grafting
 Identify endothelial damage during cataract extraction.
Methylene Blue
o Stains corneal nerves, devitalized cells, and mucus.
General Anesthetics
 Preanesthetic Medication
o For anxiety- to calm them down (i.e. diazepam)
o For drowsiness (diazepam, or scopolamine if more sleep is needed)
o For muscle relaxation- diazepam
o For pain- an opioid (morphine)
o For secretions (atropine/scopolamine)
 Stages of General Anesthesia
o Stage 1: Analgesia (conscious without pain)
o Stage 2: Delirium- lose inhibitions
o Stage 3: Surgical anesthesia- unconscious
o Stage 4: Respiratory paralysis- seen with GA OD. Avoid this stage.
 Inhalation Anesthetics
o Gases, volatile liquids. Want it to be more soluble in blood vs. air. Potency
deals with the blood air partition coefiicient.
o Proposed mechanisms of action
 Volume-expansion theorey- cells expand, closing the gates,
decreasing activity
 Binding to lipoproteins near ion channels- allosteric effect
 Increased fluidity of membranes- collapses ion channels.
 Enhancement of GABA-mediated chloride condunctance,
increasing chloride.
o Principles of administration
 Partial pressure of anesthetic gas in tissues
 Directly proportional to concentration of gas in the tissues
 Inversely proportional to solubility in that tissue.
 With increased solubility, need increased GA, therefore
increased high partial pressure.
 Rate of induction is decreased by reduced alveolar ventilation.
Need increased time with GA, because patient is not breathing as
heavily
 Rate of induction is increased by decreased cardiac output.
Exposed to GA longer and unloads longer in brain.
 The higher the blood:gas partition coefficient, the more anesthetic
gas must be dissolved in the blood to attain a particular partial
pressure

MAC (Minimum alveolar concentration/ Minimum anesthetic
concentration): Concentration that would prevent a response to a
painful stimulus in 50% of patients.
 1 MAC = ED50
 1.3MAC = ED99.99 (Surgical anesthesia)
 0.6MAC of one anesthetic + 0.7 MAC of another anesthetic
= 1.3 MAC
o 2 smaller doses used to avoid toxicity
o Agents
 Nitrous Oxide
 80%, 20% oxygen
 Also called laughing gas
 Local anesthetic for dentists
 Incomplete general anesthetic. Only goes to stage 2
 Amnesia
 Adverse effects
o Vitamin B12 deficiency
o Decreased fertility in women
 Isoflurane (Forane)
 Good muscle relaxation (pre-op)
 Depth of anesthesia can be adjusted quickly
 The most widely used inhalation anesthetic.
 Relaxes the bv, so monitor bp.
 Not as soluble in fat/blood
 Reaches 60%. Need a large loading dose
 Halothane (Fluothane)
 For kids
 Some metabolism to an allergic product. Can induce
hepatitis. Slowly induced, because highly soluble in the
blood.
 Cardiovascular depression
 Malignant hyperthermia
 Moderate muscle relaxation (dantrolene)
 Sensitizes the heart to the effects of epinephrine.
 Decreases bp
 Cause arrhythmia in presence of epinephrine or has
pheochromocytoma (additional growth of adrenal tissue
elsewhere)
 Enflurane (Ethrane)
 Good analgesia
 Skeletal muscle relaxation
 Rapidly acting
 Decreases bp
 Desflurane (Suprane)
 Moderate muscle relaxation

 Respiratory depression
 Irritating odor
 Sevoflurane
 Like desflurane but
o Not irritating
o Partially metabolized to fluoride
 Methoxyflurane (Penthrane)
 Significant amount of metabolism to fluoride
 Not widely used
 Diethyl ether
 Mainly of historical interest
 Flammable; heavier than air
 Emetogenic- causes NV
 Stimulates secretions
 Slow
Intravenously-administered Anesthetics
o Thiopental (Pentothal)
 A barbiturate
 Mechanism: enhancement of binding of GABA to GABAA
receptors, increasing the open time of chloride channels
 Used only to induce, not to maintain, because it can cause
laryngospasm and the drug is quickly redistributed (1min)
 Slight antianalgesic effect
o Propofol (Diprivan)
 Rapid onset (<1min)
 Used to induce and to maintain
o Etomidate (Amidate)
 Used only to induce
o Benzodiazepines
 Mechanism: enhancement of binding of GABA to GABAA
receptors, increasing the frequency of opening of chloride
channels.
 Diazepam (Valium)- slow onset, long duration, but not usually
used.
 Midazolam (Versed)- more common (good analgesic)
 Rapid onset
 Used to induce and to maintain- can maintain at different
levels
 Significant amnesia
o Ketamine (Ketalar)- similar to PCP
 Mechanism: Blocks cation conductance by binding to
phencyclidine receptor in the cation channel that is gated by a
glutamate receptor, thereby blocking excitation by glutamic acid
 Used only to induce
 Marked analgesic action
 Dissociative anesthesia
 Separation of person from self
 Catatonia (cant move)/ amnesia
 No muscle relaxation
o Opioids
 Morphine
 An analgesic used in conjunction with general anesthetics;
depresses the CNS
 Fentanyl (Sublimaze)
 An analgesic with significant CNS depressant ability
 Rigidity of respiratory muscles may occur after emergence
o “Lead pipe rigidity”
o Tx: naloxone, naltrexone, pancuronium
Local Anesthetics
 Definition
o Agents which depress impulse conduction along nerve fibers when applied
locally. Sleep is not induced
 Two chemical categories
o Amides
o Esters
 Absorption
o Hydrochloride salt (from manufacturer)  Free base (in tissue)
 Crosses the membrane most easily. Those that are nonionized cross
faster. The ionized form brings about the anesthetic effect.
o Free base  salts (nonionized
 Mechanism
o Blockade of Na channels (inner gate)
o There is less effect if injected.
 Order in which neuronal functions are inhibited
o Pain (small diameter, unmyelinated fibers)
o Temperature (myelinated)
o Touch (small, myelinated)
o Muscle tone (if enough injected)
o Proprioception
o Motor (large diameter)
 Fate
o Metabolism
 Amides- longer duration, because amidases only in the liver (not
blood)
 Esters- metabolized in blood and liver.
o Carried away by blood, so decreased metabolism with vasoconstriction
 Adverse effects
o CNS: Stimulation  nervousness/jitters
o Cardiovascular system: Depression
o Treatment
 Oxygen




Epinephrine
Anticonvulsants
Allergic reactions (rare)- esters increase allergies
Agents
o Injectable
 Amides
 Lidocaine (Xylocaine)
 Bupivacaine (Marcaine)
o Binds protein, therefore longer lasting
 Mepivacaine (Carbocaine)
 Etidocaine (Duranest)
 Dibucaine
 Esters
 Shorter acting
 Procaine (Novocain)
 Tetracaine (Pontocaine)
 Chloroprocaine (Nesacaine)- no longer used
o Topical
 Amides
 Lidocaine (Xylocaine, Hurricaine)- used by dentists
 Esters
 Tetracaine (Pontocaine)
 Benzocaine (Solarcaine)- OTC
 Cocaine
Topical Anesthetics
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
Mechanism of action
o Acts on the cell membrane of nerve tissue, where they decrease the
transient increase in membrane permeability to sodium. This prevents both
the conduction and generation of nerve impulses. Combination of two or
more anesthetics does not produce an additive effect, but increases the
chance of toxic reaction. Patients should never be permitted to selfmedicate with any anesthetic due to corneal disruption.
General information
o Topical anesthetics are used prior to instillation of mydriatic and
cycloplegic agents for various reasons
 Reduce stinging of cycloplegics and allows prolonged cycloplegic
contact time by decreasing tearing due to stinging. Reduce blink
rate also allows prolonged cycloplegic contact time.
 Anesthetic produces a transient keratopathy which increases the
adsorption of the cycloplegic.
o Topical anesthetics contain preservatives with antibacterial and antifungal
properties; therefore use single dose containers without preservatives prior
to culturing of ocular structures.
o Increases the effects of succinylcholine and sympathomimetics. Decreases
the effects of adrenergic blockers and sulfonamides.
Cocaine
 This is the most effective topical anesthetic for producing conjunctival anesthesia.
It provides the longest duration of corneal anesthesia and loosens the epithelium
of the cornea more than any other topical anesthetic. Unique among the topical
anesthetics in that it is also a vasoconstrictor, therefore it delays its own
absorption. Produces corneal anesthesia in 5 minutes with duration of action about
20 minutes.
 Clinical uses
o Diagnosis of Horner's or oculosympathetic paresis, corneal epithelial
debridement, and forced duction testing
 Dispensing information
 Solutions must be prepared by diluting the salt form of cocaine. Usual solutions 1,
4, and 10%.
 Toxicity
o Ocular- significant epithelial defects of the cornea, dilation of the pupil.
o Systemic- rapid, irregular pulse, nausea, vomiting, convulsions, headache,
restlessness, all with dose of 20mg. Death secondary to respiratory arrest
with 1.2g. Propanolol has been reported to be effective against the toxic
pulmonary effects of cocaine.
 Contraindications
o Patients with systemic hypertension or patients taking adrenergic agonists,
because cocaine blocks the re-uptake of norepinephrine.
o Patients taking guanethidine, reserpine, tricyclics, methyldopa, or MAOIs.
o The concomitant use of epinephrine or phenylephrine is contraindicated.
o Patients predisposed to acute closure glaucoma.
Tetracaine
 Clinical uses
o Solution- contact tonometry, gonioscopy, suture removal, and
nasolacrimal duct probing
 Toxicity
o Ocular- transient stinging, corneal epithelium compromise, and allergic
conjunctivitis
o Systemic- none reported, but possible CNS involvement with doses over
1.5mg/kg body weight
 Dispensing information
o 0.5% solution. Provides corneal anesthesia in 10-20 seconds, with duration
up to 10 minutes.
o 0.5% ointment Provides longer anesthesia, due to increased tissue contact
time.
 Contraindications
o Known allergy to tetracaine
Benoxinate
 Provides corneal anesthesia in about 10 seconds and lasts up to 10 minutes.
 Clinical uses
o Applanation tonometry
 Dispensing
o Available only in 0.4% concentration in combination with 0.25% sodium
fluorescein (Fluress). This solution is used frequently since fluoroscein
fluoresces more with benoxinate than any other topical anesthetic.
o Brand names
 Fluress or Fluorox
 Toxicity
o Ocular- same as tetracaine
o Systemic- one case of grand mal seizure possibly associated with use.
 Contraindication
o Known allergy to any component
Proparacaine
 Produces anesthesia similar to benoxinate
 Clinical uses
o Contact tonometry, gonioscopy, suture removal, nasolacrimal duct
probing, and A scan ultrasonography.
 Dispensing information
o 0.5% solution
o 0.5% solution in combination with 0.25% sodium fluorescein
o Brand name
 Ophthaine, Ophthetic, Aktaine, Procaine, Spectrocaine, Alcaine,
etc.
 May also be found in combination with fluorescein (Fluoracaine)
for tonometry.
 Toxicity
o Ocular- corneal stippling, transient corneal edema, conjunctival
hyperemia, lacrimation, allergic conjunctivitis, and edematous lids.
o Systemic- none reported. .
 Contraindication
o Known allergy to any component.
Irrigating Solutions
 These are basically any aqueous solution.
 Watch for pH, osmolarity, sterility, nutrients, and toxicity.
 Metabolic needs of anterior segment tissues
o Cornea
 Epithelium does not require glucose in extraocular solutions,
because it is stored in the tissue.
 Endothelium requires both glucose and oxygen
o Conjunctiva: acquires glucose and oxygen from vasculature




o Lens: acquires glucose and oxygen from aqueous humor.
Physiological Considerations
o Isotonicity
 Corneal endothelium tolerates 200-400 mOsm
 300 mOsm is optimal.
 Hypertonic means that the cell shrinks, hypotonic means that the
cell lyses.
o Concentrations of salts are critical for perfusion media: Na, K, Ca, Mg, Cl,
and HCO3.
 These maintain the cell’s metabolism
o Proper pH is essential (7.3-7.7). Damage occurs with <6.5 and >8.5.
Preservatives
o Prevent solution breakdown and prevent infections.
o All are microbial agents
o For extraocular solutions only; if used in intraocular solutions, they would
cause irits, cataract formation, and death of endothelial cells
o Agents
 Refrigerate to prevent irritation.
 BAK
 Damages epithelium if >0.02%, which is near the point that
is needed to kill pseudomonas.
 Thimerosal
 Damage if >0.01%, same concentration as killing bacteria.
Extraocular Irrigating Solutions
o These are “normal saline.”
o Be sure to remove the contacts first.
o Typical preparations
 Eye-Stream
 Eye Wash
 Eye Irrigating Wash
o Use: wash away foreign debris and liquids
o First-aid irrigating solutions- use copius amounts
 Saline is best
 Alkalis can penetrate the cornea.
Intraocular Irrigating Solutions
o Saline is unacceptable, because tissues need nutrients or they become
edematous.
o Balanced Salt Solution (BSS)- for short-term intraocular surgery (<1h)
o BSS Plus: BSS plus sodium phosphate, sodium bicarbonate, glucose and
glutathione disulfide.
o Clinical applications
 Miotics and mydriatics can be used in intraocular irrigating
solutions if diluted
 Viscoelastic agents help to protect the corneal endothelium
 If corneal endothelium is compromised, use BSS plus.
 Diabetic vitrectomy: add 50% dextrose (glucose) to BSS plus.
o First-aid Irrigating Solutions
 Paracentesis
 Phosphate buffer intracamerally
 Complete physiologic solution
Contact Lens Solutions
 Normal Tears
o Tonicity is equivalent to 0.95%-1.0% NaCl
 Solutions of 0.14%-1.4% are acceptable
 Solutions of 0.5%-2.0% are better
 Solutions of 0.9%-1.0% are best
o pH = 7.35-7.4
 6.6-7.8 is acceptable.
 <6.6 stings and >7.8 is uncomfortable.
 Most solutions are 4.2-8.6. Some preservatives require a lower or
higher pH
 Chlorobutanol works better below pH 7
 BAK works better about pH 7
 Buffers
o Acid/alkaline salts, such as bicarbonates, phosphates, borates, and
acetates.
o CO2 can diffuse into solution and decrease the pH to 5 without buffers.
o Bicarbonates, acetates, and citrates are volatile and reactive.
o Phosphates and borates are better
 Borate is compatible with BAK, alkaline solution, and PVA.
 Preservatives (Disinfectants)
o Benzalkonium chloride
 This is the most common.
 It increases cell membrane permeability, acting as a detergent.
 Used in solutions for polymethacrylate lenses, not hydrogel
because that material absorbs BAK.
 Concentrations: 0.001-0.01%
 High concentrations can damage the corneal epithelium.
 Optimum effect at pH 8.
 Absorbed by rubber, fibers, organic material, and sponge material.
 K, Ca, and Mg compete for binding sites.
o Chlorbutanol
 Bacteriostatic
 Used in some solutions for PMMA lenses
 Volatile
o Phenylmercuric nitrate
 Slow; not used alone.
o Thimerosal
 For solutions for rigis and hydrogel lenses; does not bind.
 Incompatible with acid, so keep above pH 7.
 Degraded by light. Store in an opaque container.



o
o
o
o
o
o
o
Binds to bacterial proteins
Not usually used alone, but do not use with BAK.
25-50% of patients are “sensitive.” They have a toxic reaction or
allergy.
Chlorhexidine
 Used in rigid and hydrogel lens solutions
 Ruptures microbial cell membrane, even killing HIV.
 Unstable in alkaline solutions, so keep in acids.
 Not usually used alone. Use with thimerosal.
EDTA and Sodium acetate
 Binds ions needed by bacteria, especially Ca, and maybe Mg.
 Not used along.
Sorbic acid
 Used in solutions for hydrogel lenses
 Best at pH 4.5. Decreased effectivity at higher pHs.
 Usually used with EDTA
 Bacteriostatic.
Tris (2-hydroxyethyl) tallow ammonium chloride
 Used with thimerosal
 Weak
Polyquad
 A quaternary compound, meaning that it is a large molecule so that
it is not absorbed.
 Mainly for hydrogel lenses.
Poly aminopropyl biguanide; polyhexamthylene biguanide HCl +
tromethamine
 This is high molecular weight so it is not absorbed.
 For hydrogel lens solutions
 Positive charge reacts with phospholipids of bacterial cell wall,
especially if G+.
 Used in concentrations of 0.00005%
Hydrogen peroxide
 The higher the concentration (>0.03%), the more discomfort.
 Solution is too acidic to use as supplied.
 Bactericidal and viricidal (kills HIV)
 Use a stabilizer, such as NaSnO2 or Na2NO2. this breaks H2O2
down into O2 and H2O.
 Platinum converts it to water and molecular oxygen. It is the
catalyst.
 Septicon system: 10 min of H2O2, then saline with a
platimum disk
 AO Sept system: disk and les in solution for 4h.
 Catalase: OxySept and Lensept system- 1min. A 2-step
process.
o Catalase is the enzyme from bovine liver
 Sodium pyruvate: 5-6min




 Sodium thiosulfate
o Sodium dichloroioscyanurate
 Not used in the US
 A solution for hydrogel lenses
 Effervescent tablets (Softab, Alcon)
o Alcohols
 Isopropyl (Mira-Flow)
 Benzyl
o Effectiveness
 Increased if the CL is cleaned and rinsed
 Do not use after expiration date. There are no preservatives, so
evaporation increases the concentration.
 All work faster at warmer temperatures. They also break-down
faster
 D-value: time to decrease organism number to 1/10th of the
original number.
 Fungi die more slowly than bacteria
 Acanthameba not well controlled by any preservative. Needs heat
disinfection.
Wetting Agents
o Needed for rigid lenses, to form a surface film
o Mucoid later forms in a few minutes
o Hydrophilic surface needed
o PVA or partially acetylated PVA- breaks down PVA and acetate. Acetate
then acts like a buffer.
o Polysorbate 80
Lubricants
o Rewetting/comfort solutions. Placed in the eye, with the CL in place.
o Inert
o Methylcellulose
o Hydroxyethyl cellulose
o Hydroxypropylcellulose
o Polyvinylpyrrolidone (PVP, povidone)
Soaking (Storage) Agents
o Usually contain a disinfectant
o To keep the lens moist
o Maintains softness and hydration of soft lenses
Cleaning Agents
o Remove protein, microbes, etc via a surfactant and by emulsifying lipids
 Proteins are dissolved more easily with an increased pH.
 These solutions do not react with the CL.
o Rubbing with water or saline is usually insufficient
o Silvo for PMMA lenses
o XPAL for rigid or hydrogel lenses.
o Nonionic surfactants
 Octoxynol


 Alcohols
o Anionic surfactants (Detergents)- for RGPs
 Debris has a + charge, so the cleaner has a – charge.
o Enzymatic cleaners
 These break down the protein via a protease.
 Papain- from papaya
 Hog pancreatic enzyme
 Substilin A and B
 Cysteine HCl is added to break the disulfide bonds.
 Enhanced by H2O2.
Polishing Compounds
o Silvo
o SnO2
o XPAL
Clinical Use of Solutions with Nonhydrogel Lenses
o Wetting solutions
 Used before lens placement
 Components
 PVA with a buffer
 Viscosity agent to increase adherence time.
 Remove lenses from soaking solution and apply wetting solution,
rub between thumb and forefinger.
o Soaking solutions
 Maintains lens hydration; prevents contamination; helps maintain
cleanliness
 Not viscous
 Use cleaning solution after wearing; then place in soaking solution
 Use fresh soaking solution everyday, as a preservative becomes
less effective.
 Some patients are sensitive to BAK in soaking solutions.
o Cleaning Solutions
 Most are nonionic surfactants
 EDTA enhances antimicrobial activity and softens water,
enhancing cleaning action.
 May contain mild abrasive- can cause PEE.
 Rub lens in palm of hand with cleaning solution; rinse with
soaking solution or saline; place in soaking solution.
 Miraflow contains alcohol- can change the shape of the lens.
 Enzymatic cleaners remove protein; once a week is sufficient.
o Combination Solutions
 Wetting-soaking
 Viscosity may be too high for soaking, or too low to wet.
 Preservative concentration may be too low.
 Cleaning-soaking- need low concentration of cleaner.
 Wetting-soaking-cleaning
 Not as effective as a separate cleaner.

 May be too viscous.
o Lubricating Solutions
 Usually isotonic or hypertonic
 Usually contain a viscosity agent
 Contain preservatives.
Clinical use of solutions and systems with hydrogel lenses.
o Absorb water-soluble substances
 Preservatives may damage the eye
 Lenses may become discolored.
o Heat disinfection (in saline) 80-90 C
 Avoids toxicity
 Usually effective
 May shorten the lens life
 Cannot be used in high water content lenses.
 May contain a bacteriostatic preservative
 Sorbic acid, EDTA, or sodium perborate
o Chemical disinfections (“Cold disinfection”)
 Thimerosal-chlorhexadine systems
 Chlorhexadine
 Alkyltriethanol ammonium chloride- Thimerosal solution
 Polyquad-preserved solution
 Polyaminopropyl biguanide
 H2O2
 Breaks down to water and oxygen
 Oxidizing agent
 Only ophthalmic solutions should be used.
 Soak lenses for 10 min in 3% H2O2.
 Neutralize after soaking
o Septicon system
o AOSept system
o Sodium pyruvate
o Sodium thiosulfate
o Catalase
o Catalase tablet system
o Rinse with saline
 Isopropyl alcohol
 Iodine systems
o Cleaning lenses
 Mechanical cleaning
 Ultrasound- less effective
 Surfactants
 Oxidizing agents- breaks down protein
 Enzymatic cleaners
 Remove protein
 Do not remove inorganic materials
 Agents
o Papain, pancreatin, substilin

Medications and CL wear
o Topical ocular medications
 Should usually be instilled without lenses in place
 May increase contact time of the drug
 Drugs may concentrate in a hydrogel lens; some drugs (e.g.
epinephrine) will discolor hydrogel lenses.
o Systemic medication
 Some drugs decrease tear production.
 Oral contraceptives may change the shape of the cornea.
 Some drugs are excreted into tears, and can be absorbed by
hydrogel lenses, causing corneal irritation or discoloring the lens.
 Disulfiram can interact with PVA from wetting solutions.
Adjunctive Agents
 Growth Factors
o General effects
 Normal turnover of many kinds of cells
 Promote wound healing
 Stimulate neovascularization
o Epidermal growth factor (EGF)
 Stimulates healing of corneal epithelium and endothelium
 Angiogenic; may contribute to neovascular disorders
o Fibroblast growth factor (FGF)
 Stimulates mitosis, chemotaxis, and cell migration
 Stimulates corneal wound healing
o Transforming growth factors (TGF) alpha and beta
 Stimulates healing of corneal epithelium, stromal fibroblasts, and
endothelium
 May provoke immune response/ allergies
 May inhibit neovascularization
 Aids in formation of chorioretinal adhesion around macular holes
o Insulin-like growth factor (IGF)
 Stimulates neovascularization
 Mitogenic in RPE
 Possibly involved with PDR.
 Botulinum Toxin
o Potential uses
 Strabismus, nystagmus, blepharospasm, hemifacial spasms,
myokymia, lower lid entropion, and corneal ulcers.
o Mechanism: interference with acetylcholine release
o Duration of action: up to nine months
o Adverse effects
 Diplopia, ptosis
 Viscoelastic agents
o Macromolecules
o Purpose: protect ocular tissues during surgical procedures. It separates and
lubricates the tissues.
o Sodium Hyaluronate (Hyaluronic acid)
 Actions
 Stimulates neutrophil function
 Stimulates cell proliferation, aggregation, and migration
 May facilitate wound healing
 Uses
 Protection during surgery
 Treat dry eye
 Adverse effects
 Elevation of IOP
 Postoperative inflammation
 Particulate formation
 Corneal haze formation
 Allergic reactions
o Chondroitin sulfate
 Use (in combination with hyaluronate): anterior segment surgery
 Adverse effects
 Allergic reactions
 Decrease in corneal thickness
 Increased post-op IOP.
o Hydroxypropylmethylcellulose
o Collagen- used with anterior seg surgery
o Silicone oil- for RD and vitrectomy. Remove within 1 year.
Chelating agents
 Binds metals or minerals to prevent absorption and/or damage
 British Anti-Lewisite (BAL)
o Aka Dimercaprol
o Ophthalmic use: prevent corneal damage from arsenic compounds, such as
lead or mercury
o Preparations
 Ointment and solution
 Deferoxamine
o Binds to iron (treat for iron poisoning)
o Ophthalmic use: treat corneal rust rings
o Adverse effect: cataract formation
 Ethylenediaminetetraacetate (EDTA)
o Binds to Ca, Fe, Pb, etc.
o Ophthalmic use: remove corneal deposits of calcium
Tissue Adhesives: experimental
Surgical Miotics
 Acetylcholine
o Preparation 1% solution
o Placed directly onto the iris
o Short-acting
 Pilocarpine
o Longer acting
o Applied to the cornea
 Carbachol
OTHER
Inderal (Propanolol)
 Mechanism of action
o Competitive non-selective beta receptor antagonist agent. Decreases heart
rate, depresses AV conduction, reduces cardiac output, decreases bp,
induces bronchospasm, constricts vascular smooth muscle, decreases beta1 mediated release, increases sodium and water retention, decreases
glycogenesis, and slows post-insulin recovery of glucose.
 Dosage
o Tablets, IV, sustained-release capsules
o 10-160mg
o Typical dosage: 120-140mg/day in divided dosage.
 Indications
o HTN, cardiac arrythmias, angina, hypertrophic sub-aortic stenosis,
decrease post-MI mortality, pheochromocytoma, and migraine
prophylaxis.
 Contraindications
o CHF, bronchospastic disease, labile DM, hyperthyroidism, impaired renal
and liver disease, hypotension, bradycardia, and digitalis therapy.
 Side effects
o Systemic: impotence, rebound hyperemia, sedation, depression,
bronchoconstriction, short term memory loss, nausea, emesis, diarrhea,
dry mouth, hyperglycemia, weight gain, CHF, hypotension, bradycardia,
hallucinations
o Ocular: decreased IOP, blurred vision, orbital pseudotumor, diplopia,
myasthenic muscular block, ptosis, EOM paresis, oculomucocutaneous
syndrome, erythema multiforme.
Tramadol HCl (Ultram)
 A centrally acting analgesic. This is not an NSAID.
 Mechanism of action
o 2 complementary mechanisms
 weak binding to opioid receptors
 inhibition of reuptake of norepinephrine and serotonin.




Dosage
o 1-2 50mg tabs q4-6h or prn, not to exceed 400mg/day (or 300mg/day in
patients over 75 years)
Indications
o To control moderate to moderately severe pain without side effects of
narcotics. Also, less potential for drug abuse. First drug of choice when
physicians want better pain control.
Contraindications
o Ultram should not be administered to patients with previous sensitivity to
tramadol or in acute intoxication with alcohol, hypnotics, centrally acting
analgesics, opioids, or psychotropic drugs.
Side effects
o Constipation, nausea, dizziness, HA, somnolence, and vomiting.
Diphenhydramine (Benadryl)
 Mechanism of action
o Antihistamine drug with anticholinergic and sedative properties. Competes
with histamine fro cell receptor sites. Has additive effects with alcohol.
 Dosage
o 25, 50mg tablets, IV
o typical dosage: 25-50mg tid or qid
o Peak activity: 1hour. Duration: 4-6 hours.
 Indications
o Antihistamine- allergic conjunctivitis, urticaria, angioedema, anaphylactic
reactions.
o Motion sickness and night time sleep aid
o Anti-parkinsonism
 Contraindications
o Newborn infants
o Nursing mothers
o Concurrent use with MAOIs.
 Caution
o Narrow angles, peptic ulcers, pyloroduodenal obstruction, prostatic
hypertrophy, bladder obstruction, asthma, hyperthyroidism, cardiovascular
disease, HTN, increased IOP.
 Side effects
o Systemic: urticaria, rash, anaphylactic shock, chills, dry nose, dry mouth,
hypotension, HA, tachycardia, palpitations, anemia, thrombocytopenia,
agranulocytosis, sedation, drowsiness, fatigue, insomnia, euphoria,
epigastric distress, anorexia, nausea, tinnitus, diarrhea, early menses,
difficult urination, thickening of bronchial secretions.
o Ocular: diplopia, blurred vision, decreased lacrimation, mydriasis,
erythema, sub-conjunctival hemes, anisocoria, decreased accommodation.
Theophylline (Theo-dur, Slo-bid, Slo-phyllin, Theo-bid)
 Mechanism of action




o A methylxanthine bronchodilator which acts by directly relaxing bronchial
smooth muscle and pulmonary vasculature. It also stimulates the central
respiratory center. It acts by inhibiting phosphodiesterase which results in
an increase in cAMP.
Dosage
o 50-300mg time-released capsules and tablets.
o Dosage: 1 tab po qd-tid on an empty stomach
o Po/pr
Indications
o Treatment of chronic, reversible bronchospasm associated with asthma,
bronchitis, emphysema
o Maintenance therapy for moderate to severe asthma.
o Slow onset limits its use in acute situations.
Contraindications
o Patients with seizure disorders
o Cardiovascular disease
o Peptic ulcer disease
o Renal and liver disease
o HTN
o Hyperthyroidism
o Influenza
o Elderly patients
o Used in caution in patients on xanthine medication, beta blockers, and
erythromycin.
o Hypoxemia
Side effects
o No ocular side effects
o Systemic: nausea, vomiting, HA, insomnia, tachycardia, muscle twitching,
convulsions, arrythmias, diarrhea, hypotension, hyperglycemia, diuresis,
and fever.
Pyrimethamine (Daraprim)
 Mechanism of actions: folic acid antagonist
o An antimalarial drug which acts to inhibit dihydrofolate reductase. This
enzyme is needed to catalyze dihydrofolic acid to tetrahydrofolic acidimportant compound for cellular growth.
 Dosage
o 25mg tablets.
o Prophylaxis: 25mg/week for adults
o Acute malaria: 25-50mg for 2 days.
o Toxoplasmosis: loading dose= 75-150mg followed by 25-50mg daily x4-6
weeks (1-2weeks if quadruple treatment).
 Indications
o Malaria prophylaxis
o Used in combination with sulfonamides for acute attacks of malaria.
o Toxoplasmosis- triple sulfonamides and daraprim.

Side effects
o When used at 25mg/wk dosage, no significant side effects.
o Megaloblastic anemia
o Leukopenia
o Thrombocytopenia
o Pancytopenia
o Vomiting
o Convulsions
o Ocular: none.
Thoridazine (Mellaril)
 A phenothiazine antipsychotic medication which acts by blocking D2 dopamine
receptors. This suppresses all D2 receptor activity in the brain. It is effective in
reducing excitement, hypermotility, agitation, and affective tension.
 Dosage
o 10-200mg tablets po
o starting dose: 50-100mg tid po
o max dose: 800mg/day
 Indications
o Psychosis
o Schizophrenia
o Mania
o Severe behavioral problems in children
 Hyperexcitability, combativeness, hyperactivity.
 Contraindications
o Impaired renal function (caution)
o Cardiovascular disease
o Respiratory disorders
o Narrow angles
o Severe CNS depression.
 Side effects
o Retinal toxicity
 Drug binds to the melanin in the uveal tract and subsequently
damages the choriocapillaris and the RPE. This may 1st present in
months 1-3 on the therapy. This is based on daily dosages.
Pigmentary disturbances originate in the periphery and move
toward the posterior pole. Fundus can be “peppery” in mild cases
while developing large plaque lesions, pigmentary changes, and
choroidal atrophy in severe cases. Retinal vascularture and optic
disk remain normal. The RPE is affected and EOG findings are
attenuated as the toxicity increases. Mild changes in retinal
function may reverse but pigmentary changes are permanent.
Progression of retinopathy may occur years after discontinuation of
the drug.
 800mg/day or less is a safe dosage
 quick onset may occur is high daily doses are administered.



Subsequent side effects
 Contracting VF
 Ring scotoma
 Decreased dark adaptation
 Decreased VAs
 Decreased color vision
o Mydriasis
o Decreased accommodation
Management
o Fundus evaluation within the first 2-4 months. VA, static threshold VF,
fundus photographs, and color vision for baseline.
o Fundus evaluations every 6 months.
o Electrodiagnostics are of no value in early detection
o Discontinue if toxicity develops.
Systemic side effects
o Neuroleptic malignant syndrome- altered mental and autonomic nervous
system function
o Tardive dyskinesia
o Drowsiness
o Dry mouth, nausea, vomiting, diarrhea
o Galactorrhea, breast enlargement
o Inhibition or retrograde ejaculation
o Dermatitis
o Peripheral edema
o Electrocardiogram changes
o Leucopenia
o Seizures
Thorazine (Chlorpromazine)
 Mechanism of action
o Same as thioridazine. Antipsychotic phenothiazine.
 Dosage
o Tablets, syrup, capsules, IV, suppositories
o 10-200mg tablets
 Indications
o Psychotic disorders
o Control manic phase
o Intractable hiccups
o Acute intermittent porphyria
o Pre-op medication
o Severe behavioral problems
 Contraindications- use with caution
o Impaired liver function
o Cardiovascular disease
o Chronic respiratory disorders
o Narrow angles

Side effects
o Systemic: same as thiroidazine
o Ocular
 Irreversible anterior lens capsule deposition- stellate pattern. Long
term high dose therapy (>500mg/day).
 Corneal deposition- endothelium and Descemet’s
 Reversible retinal pigmentation with high dose therapy.
 Decreased accommodation
 Mydriasis
 Blurred vision
 Decreased lacrimation
o 1200-2400mg/day for 12 months can produce toxicity. Follow every 6
months.
Hydroxychloroquine (Plaquenil)
 Mechanism of action
o Antimalarial agent which belong to the 4-aminoquinolone family. It is the
quinolone agent of choice for RA.
 Dosage
o 200mg tablets
o typical dosage: 400-600mg/day
 Indications
o Antimalarial- acute attacks and suppressive treatment
o Discoid and systemic lupus
o RA
 Contraindications
o Long term in children
o Hypersensitivity to 4-aminoquinoline compounds
o Presence of ocular changes attributed to aminquinoline use.
o Pregnant females
o Caution in hepatic disease, hepatotoxic drugs, alcoholism, and psoriasis.
 Side effects
o Systemic: irritability, nervousness, psychosis, HA, vertigo, tinnitus, ataxia,
skeletal muscle weakness, decreased deep tendon reflexes, alopecia,
pruritis, erythema, blood dyscrasias, nausea, psoriasis, weight loss.
o Ocular: disturbed accommodation, transient corneal edema, corneal
hypesthesia, corneal deposits, EOM paresis, blurred vision
o Retina: “Bulls eye maculopathy”, edema, atrophy, pigmentary changes,
increased photostress response, decrease in rod sensitivity, optic disc
pallor and atrophy, vessel attenuation, color vision loss and VF defects.
o Quinoline toxicity first produces fine mottling within the macular area
which may spare the foveal reflex. Shallow VF defects may manifest prior
to visible changes. As the pigmentary changes occur, zones of concentric
hyperpigmentation adjacent to zones of depigmentation occur which
produces the classic “Bulls eye” pattern. As the disease progresses, severe
cases may produce vessel attenuation, and disc pallor. It is typically

symmetrical between the fellow eyes. Peripheral RPE hyperplasia in some
patients can produce “pseudoretinitis pigmentosa.” However, dark
adaptation will show normal or slightly decreased findings. VF changes
usually correlate with fundus appearance. Paracentral scotomas may
connect to form ring scotomas. ERG findings may become extinguished
over time. Early electrodiagnostic testing is equivocal. Macular lesions
may resemble a macular hole or ARMD.
o Drug binding within the neurosensory retina is believed to be the
mechanism of retinal toxicity. Accumulation leads to destruction of the
various layers including photoreceptors and the RPE. Hydroxychloroquine
does not have as high a risk for development of retinopathy. Cumulative
dosage exceeding 800g greatly increases the likelihood of developing
retinopathy or more than 750mg/day over months to years.
Discontinuation of the drug may not stop slow progression of retinal
changes. Retinal toxicity is minimal if daily dose <6.5mg/kg body weight
or id duration of treatment <10 years.
Management
o Patients should be followed at 6 month intervals. Baseline findings for
VA, color vision, static threshold VFs, and fundus appearance should be
documented. Fundus photography would be additional support. Elderly
patients have less clearance of the drug and should be monitored carefully.
Fluorescein angiography may be a helpful tool in Ddx.
Chloroquine (Aralen Hydrochloride)
 Mechanism of action
o Similar to hydroxychloroquine
 Dosage
o 500mg tablets.
 Indications
o Suppressive treatment of malaria
o Acute attack of malaria
o Extraintestinal amebiasis
 Contraindications
o Same as hydroxychloroquine
 Side effects
o Same as hydroxychloroquine
o Ocular: more likely to produce retinopathy. Cumulative grom dosage
plays a large role. Risk increases when the gram dosage exceeds 300g. it
can develop with as little as 100g but typically takes 2-4 years.
 Management
o Same as hydroxychloroquine
Chlorpheneramine Maleate (Chlortrimeton)
 Mechanism of action




o Alkylamine H1 antihistamine with low-moderate sedative effects,
moderate anticholinergic activity, and low GI upset. Blocks H1 receptor
sites which bind histamine, the mediator of immune resoponse.
Dosage
o Tablets: 4, 8, 12mg
o Adults: maximum dosage up to 24mg/day. tid-qid dosage
o Children: max dosage of 12 mg.
Indications
o Hay fever
o Colds and upper respiratory allergies
o Allergic conjunctivitis
o Angioneurotic edema of the eyelid
o HZ skin manifestations
Contraindications
o Narrow angles
o Enlarged prostate gland
o Asthma
Side effects
o Ocular: dry eye, diplopia, hallucinations, decreased vision, mydriasis,
SPK, lacrimation, blepharospasm, subconjunctival hemorrhage,
anisocoria, field constriction, and retinal hemes.
o Systemic: urticaria, facial dyskinesia.
Non-sedating Oral H1 Antihistamines
 Types
o Terfenadine (Seldane) 60mg bid
o Astemizole (Hismanal) 10mg qd
o Loratidine (Clariten) 10mg qd
o Cetirazine (Zyrtec) 10mg qd
 Caution
o Seldane and Hismanal should not be given to patients already taking
macrolides (such as erythromycin, azithromycin, and clarithromycin) and
antifungals (ketoconazole and itraconazole). Can cause cardiovascular side
effects, called “Torades de Pointes,” especially in elderly patients.
Antipsychotic Agents
 These are major tranquilizers used to treat schizophrenia, a condition
characterized by hyperactivity, delusions, emotional withdrawal, and
hallucinations. They improve the mood and behavior of psychotic patients
without excessive sedation and without causing drug dependence.
 Psychoses are not cured by antipsychotic agents, but the drugs do relieve signs
and symptoms in a large percentage of affected individuals.
 The person is out of touch with reality. Always used with classic psychotherapy.
Good with catatonia
 General principles



o These drugs are also called major tranquilizers and neuroleptics. They
cause drowsiness.
o They decrease the severity of psychotic symptoms without necessarily
causing significant sedation.
Agents
o Tricyclics: Phenothiazines
 These are the most widely used because there are fewer
extrapyramidal effects.
 Chlorpromazine (Thorazine)
 Decreased hypothalamic control of body temperature
 Prochlorperazine (Compazine)
 Also treats nausea
 Thioridazine (Mellaril)
 Causes EPs
 Trifluoperazine (Stelazine)
 Fluphenazine (Prolixin, Permitil)
 Perphenazine (Trilafon)
 Piperacetazine (Quide)
 Triflupromazine (Vespirin)
o Heterocyclics: Others
 Haloperidol (Haldol)
 “Vitamin H.” very common, especially in nursing homes.
 Chlorprothixene (Taractan)
 Loxapine (Loxitane)
 Thiothixene (Navene)
 Risperidone (Risperdal)
 Clozapine (Leponex, Clozaril)- very toxic.
 Butyrophenones
 Dihydriondolones
 Dibenzodiazepines
Mechanism: blockade of D2 (DA) receptors in the mesolimbic and mesofronttal
systems.
o Associated with G1 and Go receptors that deal with inhibition.
Actions
o Takes awhile to see any effect (2 weeks).
o Calm excited patients, cause psychomotor slowing, emotional quieting,
and psychic indifference to the environment. They may or may not have a
sedative effect, but it is not hypnotic.
o Make withdrawn psychotic patients more accessible (catatonics available
for psychotherapy)
o Decrease response to thought disorder (increase indifference)
o Decrease spontaneous motor activity
o Experimental animals: decreased conditioned avoidance behavior
o Add to CNS depression of sedatives and opiates
o Alter temperature-regulating ability (regulates hypothalamus)



o Relieve nausea- depresses the chemoreceptor trigger zone (CTZ) in the
brain.
o Relieve itching
o Block histamine response.
Uses
o Schizophrenia
o Manic states
o Dementia
o Delirium
o Nausea
o Itching
o Histamine response
o Decrease body temperature in surgery
Adverse effects
o These drugs are potent antiemetics that can produce significant toxic
effects, such as parkinsonism.
o Neuroleptic Malignant Syndrome: muscular rigidity, changes in body
temperature, hypotension, confusion, coma.
o Tardive dyskinesia (bad movement of various muscles  twitching)
 Onset time- at least 3 months
 Incidence: 20% of patients at one year
 Plateaus at around 4 years
 Stops with stop of medication
o Endocrine changes: galactorrhea, amenorrhea, and impotence, due to
blockade of pituitary dopamine.
o Seizures
o Contact dermatitis
o Postural hypotension from alpha adrenoreceptor blockade
o Chlorpromazine, thioridazine
 Sedation
 Cholinergic blockade  dry mouth, etc
 Extrapyramidal effects (in a few patients). Looks like Parkinson’s
o Trifluoperazine, haloperidol, thiothixene
 Less sedation
 Less cholinergic blockade
 EPS more prevalent
Clozapine (Clozaril): A Serotonin-dopamine antagonist
o Mechanisms
 Blockade of D4 receptors in the limbic area and the frontal cortex
 Blockade of serotonin receptors
o Uses (last resort. Only works in ½ of patients)
 Resistant schizophrenia
 Psychoses in patients intolerant of other agents
o Adverse effects
 Agranulocytosis in 1-2% of patients. Weekly blood counts are
required by law.




Sedation
Sialorrhea- salivation
Tachycardia
No EPS
Drugs for Affective Disorders (Antidepressants)
 A simple definition of depression is sadness of duration and intensity that makes
it incapacitating. Emotional complaints include apathy, guilt, self-reproach,
disinterest in work or family, and preoccupation with tragedy of death. Physical
complaints include abnormal eating and sleeping patterns, fatigue, headache, and
ague gastrointestinal disturbances. Most function to enhance neurotransmitter
activity.
 Agents for “Simple” Depression (no elation, aka “unipolar”) 6-10% of population
o Tricyclic and tetracyclic antidepressants
 Most widely used medications in the treatment of depression.
 Agents
 Amitriptyline (Elavil, Amitid, Amitril)
 Amoxapine (Asendin)
 Desipramine (Norpramin)
 Doxepin (Sinequan)
 Imipramine (Tofranil)
 Maprotiline (Ludiomil)
 Nortriptilyne (Aventil)
 Protriptilyne (Vivactil)
 Clomipramine (Anafranil)
 Trimipramine (Surmontil)
 Possible mechanisms
 Start with a prescription of one week to make sure they
don’t commit suicide (wait to take an effect). Onset of the
beneficial effects can be three weeks or more.
 Indirect adrenergic action by blockade of reuptake of NE
and serotonin in the CNS
o 5HT1- therapeutic effect
o 5HT2- side effects
o 5HT3- GI Side effects
 Down-regulation of beta receptors (function unknown)
 Cocaine blocks NE reuptake but not an antidepressant. Just
a stimulant.
 Onset time: 2-3 weeks; full effect in 4-6 weeks
 Adverse effects- occur less frequently than with the structurally
related phenothiazines.
 Dry mouth
 Urinary retention
 Blurred vision
 Constipation
 Memory impairment
 Orthostatic hypotension
 Cardiac depression
 Sedation
o Monoamine Oxidase Inhibitors
 Structurally related to amphetamines.
 Agents
 Phenelzine (Nardil)
 Tranylcypromine (Parnate)
 Isocarboxazid (Marplan)
 Possible mechanisms: inhibition of catabolism of NE and serotonin
in the presynaptic nerve terminal.
 Want to block MAO-A (decreases NE vs. MAO-B which
decreases DA)
 Onset time: 2-3 weeks; full effect in 4-6 weeks
 Adverse effects
 Interaction with tyramine (increases NE, therefore
increases blood pressure). In aged (over ripe) food
 Interactions with other drugs
 Serotonin Syndrome
o Excess serotonin can lead to an overdose 
rigidity, atrophy, coma, increased temperature, etc.
 HTN, agitation, convulsions
o Atypical Antidepressants (2nd generation)- Selective for serotonin
 Agents
 Bupropion (Wellbutrin)
o DARI
o Aka Zyban to stop smoking
 Fluoxetine (Prozac)
o Aka Sarafem- for PMDD (PMS)
o An SSRI
 Trazodone (Desyrel)
 Sertaline (Zoloft)
o An SSRI
 Nefazodone (Serzone)
 Venlafaxine (Effexor)
o An SSRI
 Esatalopram (Lexapro)
o An SSRI
 Citalopram (Celexa)
o An SSRI
 Possible mechanisms
 Blockade of reuptake of NE and serotonin
 Down-regulation of beta receptors
 Onset time: 2-3 weeks; full effect in 4-6 weeks
o Selective Serotonin Reuptake Inhibitors (SSRIs)
 Greater safety
 Agents
 Fluoxetine (Prozac)
 Lertaline (Zoloft)
 Paroxetine (Paxil)
o Agents for Bipolar Disorders
 Lithium
 Mechanism: inhibition of breakdown of inositol 1phosphate
o IP1  Inositol  PI  PIP  PIP2  PLC 
DAG  Effects
 Competes with sodium
 Adverse effects
o Fine tremor
 Prevent with beta blocker
o NVD
o Elevation of TSH
o Polyuria
 Usually goes away with time, but can cause
kidney damage
 Carbamazepine (Tegretol)
 Valproic Acid (Depakene)
 Calcium Channel Blockers
Antianxiety Drugs (Anxiolytics)
 These are also known as minor tranquilizers. Have a spectrum of activity in
humans similar to barbiturates and ethanol. They are sedatives, anticonvulsants,
muscle relaxants, and potential inducers of drug dependency.
 Combinations of anti-anxiety agents should be avoided, and people taking
sedatives should not drink alcohol and use OTC medications concurrently.
 Benzodiazepines
o Most common
 Advantages include
 Relatively high therapeutic index
 Low risk of drug interactoins based on enzyme induction
 Slow elimination rates, which favors long-term CNS effects
 Low risk of physical dependence (minor withdrawal
symptoms)
 Disadvantages include
 Tendency to develop psychologic dependence
 Formation of active metabolites which can cause
cumulative CNS effects
 Higher cost
o Agents


Chlordiazepoxide (Librium)
Diazepam (Valium)
 Mechanism of action
o Exerts its influence upon the limbic system
(thalamus, hypothalamus) and reticular formation.
There is no peripheral autonomic blocking activity.
Potentiates the action of GABA and CNS inhibitory
transmitters
 Dosage
o Tablets, sustained-release capsules, IV
o 2-15mg tablets
o typical dosage: 2-10mg tid or qid
 Indications
o Anxiety disorders
o Acute alcohol withdrawal
o Pre-op for patients with apprehension and anxiety
o Adjunct in the relief of skeletal muscle spasm
o Adjunct in the relief of convulsions
 Contraindications
o Phenothiazine, MAOIs, narcotics, barbiturates, and
antidepressant therapy which may potentiate the
action of valium (caution). Also alcohol use.
o Impaired renal and liver function
 Side effects
o Systemic: drowsiness, fatigue, ataxia, confusion,
syncope, insomnia, vertigo, slurred speech,
hallucinations, hyperexcitability, constipation,
nausea, hiccups, bradycardia, hypotension,
cardiovascular collapse, menstrual irregularities,
urinary retention, urticaria, rash, neurtopenia,
decreased respiration, jaundice, psychological and
physical dependence.
o Ocular: decreased accommodation, blurred vision,
hypesthesia, decreased depth perception, decreased
EOM motility, diplopia, conjunctivitis, mydriasis.
 Oxazepam (Serax)
 Prazepam (Centax)
 Lorazepam (Ativan)
 Chlorazepate (Tranxene)
 Alprazolam (Xanax)
 Halazepam (Paximpam)
o Mechanism
 Bind to GABAA receptors on chloride channels
 This enhances GABA binding
 This increases the frequency of opening chloride channels
 This allows more chloride to enter the neuron




 This hyperpolarizes the neuron
 This impairs impulse generation
o Uses
 Anxiety
 Alprazolam: panic attacks- fast acting, then subsides.
 Muscle relaxation- good preoperatively
o Metabolism
 Most are converted to the desmethyl derivative
 Most are metabolized to desmethyl diazepam
 Desmethyl diazepam is metabolized to oxazepam
 Oxazepam is glucuronidated.
o Adverse effects
 Drowsiness: CNS depression adds to that of other depressants
 Nausea
 Treat acute overdose with flumazenil (Romazicon)
 Dependence: abrupt withdrawal can precipitate anxiety, insomnia,
and convulsions (due to decreased GABA)
 Tolerance
Busprione (BuSpar)
o Mechanisms
 (Partial) agonism of 5-HT1A receptors
 Binding to DA receptors
o Relieves anxiety without causing drowsiness
Phenobarbital (Luminal)- more for epilepsy
o Longest acting
o A barbiturate
o Mechanism
 Bind to GABAA receptors on chloride channels
 This enhances GABA binding
 This delays closing of chloride channels
 This allows more chloride to enter the neuron
 This hyperpolarizes the neuron
 This impairs impulse generation
o Induces the activities of hepatic drug-metabolizing enzymes (i.e.
cytochrome P450)
o Adverse effects
 Drowsiness (long acting)
 Rash
 Respiratory depression (this causes death with overdose)
 Tolerance (need increased dosing) and Cross Tolerance (if you
move to another drug, you need even a higher dose)
 Dependence (will have a withdrawal symptom)
Meprobamate (Miltown)
o More of a muscle relaxant
o Rare. Does not work as well.
Chloral Hydrate (Noctec)


o For acute anxiety; may be used preoperatively.
o Metabolized to trichloroethanol (another depressant)
o Adverse effects
 CNS depression; coma
 GI irritation- tastes bad
 Tolerance; break in tolerance (can no longer metabolize)
 Dependence
 Addiction
 Overdose leads to respiratory depression
Beta-blocking drugs (e.g., propranolol) can be used as an anxiolytic agent when
anxiety is related to sympathetic nervous system overactivity.
Clonidine, the antihypertensive drug, has also been used in the treatment of panic
attacks.
Drugs for Sleep Disorders
Soporifics/Sedative Hypnotics- Promote sleep
 Although acting by different mechanisms, members of this group produce a
characteristic sequence of dose-dependent effects. These include, beginning with
low doses
o Sedation- dishinhibition, relief from anxiety
o Hypnosis- sleep, with decreased REM
o Anesthesia- CNS depression
o Coma
o Death
 Sedative hypnotics may be classified by the relative slope of their dose response
curves. Ethanol, one of the earliest sedative hypnotics, also has one of the steepest
curves. Benzodiazepines, discovered in the 1960s, have the shallowest curves, and
are therefore considered to be amongst the safest members of the group.
Barbiturates have a fairly steep curve, falling midway between these two groups.
 Agents
o Benzodiazepines
 Agents
 Flurazepam (Dalmane)- very common (long)
o This is the first benzodiazepine hypnotic introduced
in the US.
o Some daytime sedation noted because of long
elimination time.
 Triazolam (Halcion) (Short)
o Ultrashort slimination half-life.
o Less daytime drowsiness.
 Lorazepam (Ativan)
 Temazepam (Restoril) (Intermediate)
 Flunitrazepam- Date Rape Drug
 Diazepam, Chlordiazepoxide, Midazolam, Oxazepam,
Alprazolam, and Chlorazepate.

Mechanism: increased frequency of opening of chloride channels
by enhancement of binding of GABA to the GABA-A receptor.
More Cl hyperpolarizes the neuron, decreasing its activity.
 Rapid rate of absorption with rapid onset.
 The more lipophilic the drug, the more CNS effect the drug
has.
 Metabolized in the liver.
 Some benzodiazepines develop active metabolites.
 Adverse effects
 Triazolam: amnesia
 Dependence
o Barbiturates
 From barbituric acid
 These cause tolerance rapidly and have a low margin of safety.
 Abstinence syndrome can develop.
 Agents
 Pentobarbital (Nembutal)
o Intermediate acting
 Secobarbital (Seconal)
o Short acting (3-4 hr) due to
redistribution/metabolism
 Phenobarbital (Long)
 Amobarbital (Intermediate)
 Thiopental (Ultrashort)
 Mechanism: delayed closing of chloride channels by enhancement
of binding of GABA to the GABA-A receptor
 Depresses activity of all brain cells.
 More selective depression of reticular activating system
posterior hypothalamus, the amygdaloid complex, and
certain limbic structures, i.e. hypocampus.
 Run entire spectrum of ultrashort acting to more prolonged
 Rapidly develop tolerance and abstinence syndrome after
becoming drug dependent.
 Very narrow margin of safety (e.g. just 10 therapeutic dose
is lethal). In 1976, 14.5% of drug related deaths in drug
abuse warning network.
 Actions terminated by metabolism (excretion through kidneys)
 Adverse effects
 Suppression of REM sleep
o 20% min of REM needed to function. REM
Rebound- >30% REM. Too much. Feel tired.
 Respiratory depression; treat with artificial respiration and
oxygen.
 Tolerance and cross-tolerance
 Dependence

 Addiction
o Zolpidem (Ambien)
 Approved fro short-term treatment of insomnia (1-2 week)
 Adverse effect: daytime drowsiness
o Chloral Hydrate
 Adverse effects
 Suppression of REM sleep
 Tolerance
 Break in tolerance
 Dependence
 Addiction
o Paraldehyde
 Also used in controlling ethanol withdrawal syndrome
 Contraindication: use of disulfiram (Antabuse)
 25% excreted through the lungs (pungent odor)
o Scopolamine
 May suppress REM sleep
 Often used presurgically
o Meprobamate
o H-1 Blockers
 Agents
 Diphenhydramine (Benadryl)
 Chlorpheniramine (Chlortrimeton)
 Adverse Effects
 Tolerance
 Excessive CNS depression
 Dryness of mouth and eyes
o L-Tryptophan
 Metabolized to 5HT (promoting sleep)
o Other lesser groups such as carbamates, quinazolines, alcohols, and cyclic
ethers do the same thing.
Agents Used to Postpone Sleep
o All are CNS stimulants, and their effects can be followed by postictal
depression. Stimulation especially seen in the cortex. There is increased
alertness and wakefulness. It stimulates the medulla to increase respiration
and stimulates the cord, causing seizures.
o Dextroamphetamine (Dexedrine, D-amphetamine)
 Stimulates the sympathetic receptors and increases the release of
NTs.
 Uses
 Treat narcolepsy
 Treat attention deficit hyperactivity disorder (ADHD)
 Mechanisms
 Direct sympathetic agonism (alpha receptors increase NE)
 Increased release of NT

o
o
o
o
Can be methylated to methamphetamine (speed)
o Cause confusion, delirium, and mydriasis.
 Adverse effects
 Tachycardia
 Irritability
 Paranoia
 Schizophrenia-like syndrome
 Convulsions
 Tolerance
 Dependence
 Addiction
 Postictal depression treated with Librium, a CNS
depressant.
Methylphenidate (Ritalin)
 Uses
 Treat narcolepsy
 Treat ADHD
 1 qday x9mo
Pemoline (Cylert)
 Uses
 Treat narcolepsy
 Treat ADHD
 1 qday
Caffeine
 A methylxanthine
 Found in coffee, tea, and chocolate
 Mechanism: unknown
 Uses
 Maintain wakefulness
 Treat apnea in pre-term infants
 Treat HA
 TID 100mg (10g can be fatal)
 Adverse effects
 Acute
o Insomnia
o Nervousness
o Cardiac arrhythmias
o Convulsions
 Chronic
o Insomnia
o Nervousness
o GI irritation (especially with a previous ulcer)
o Mild dependence
o Osteoporosis
Theobromine
 Stimulant in chocolate
o Theophylline
 Stimulant in tea
Drugs For Movement Disorders
 Agents Used in Treating Parkinson’s Disease
o Parkinsonism is characterized by a combination of rigidity, bradykinesia,
tremor, and postural instability that can occur for a wide variety of reasons
but it is usually idiopathic. The concentration of dopamine in the basal
ganglia of the brain is reduced in Parkinsonism. In idiopathic
Parkinsonism, dopaminergic neurons in the substantia nigra that normally
inhibit excitatory cholinergic cells in the corpus striatum are lost.
o Pathology
 Degeneration in the substantia nigra that secrete dopamine
 Idiopathic. Possibly:
o Flus/cerebral hypoxia
o Designer Demoral aka MPPP (a drug)  MPTP 
MPP+, via MAO-B, attacking DA
 Vs. ExtraPyramidal Syndrome
o Has Parkinsonian-like symptoms
o Caused by Thioridazine (Mellaril) and other
phenothiazines
 Symptoms
 Tremor. Pill rolling (at rest)
 Rigidity. Ratchet. Muscles rest in jerks.
 Bradykinesia. Slow movement
o Shuffling gait.
o En bloc- turn the entire body at once, vs. head first.
o Akinesia- no movement, because too difficult to
initiate.
 Dry eyes due to decreased blinking.
 Micrografia (write large  small)
 Microphonia (loud  whisper)
o Levodopa (Larodopa)
 Often referred to as L-dopa.
 Dopamine does not cross the blood brain barrier, so it has no
therapeutic effect on Parkinsonism if given into the peripheral
circulation. However, levodopa is the immediate metabolic
precursor of dopamine which can penetrate the brain and
decarboxylate to dopamine, increasing dopamine concentrations in
the basal ganglia, causing less tremor, rigidity, and bradykinesia.
 Crosses membranes readily
 Can be given orally
 Enters the CNS from the blood- activates D2 receptors.

o
o
o
o
Metabolized by dopa decarboxylase to dopamine, which does not
cross the BBB.
 Less rigidity and bradykinesia, but tremor may persist (hard to
overcome)
 70% metabolized in the gut, 28% in periphery, 2% goes to brain.
 With B6 vitamins, more goes to the periphery.
 Adverse effects
 NVD, if not taken with meals, because it is in decreased
concentrations.
 CNS: confusion, delirium, choreoathetosis
(grimacing/bobbing head), hallucinations
 Postural hypotension
Carbidopa (Lodosyn)
 Always taken with L-Dopa (does not do anything alone)
 Competes with levodopa for dopa decarboxylase peripherally,
inhibiting levodopa decarboxylation outside the CNS.
 Decreases the peripheral metabolism of levodopa
 Increases the amount of levodopa available for CNS absorption
(decreased side effects)
 Sinemet = levodopa + carbidopa
 40% goes to the gut, 50% to the periphery, and 10% to the brain.
 Vitamin B6 has not effect
Dopamine receptor agonists (D2)
 The enzymes responsible for synthesizing dopamine are depleted
in the brains of Parkinsonism patients. Therefore, drugs acting
directly on dopamine receptors may have a beneficial effect
additional to that of levodopa.
 Bromocriptine (Parlodel): stimulant of D2 receptors
 This is an ergot derivative and the most promising group of
dopamine agonists today.
 Pergolide (Permax): stimulates D1 and D2 receptors equally
 The drug may benefit patients not receiving levodopa. It
also prolongs the response to levodopa in patients with
response fluctuations.
 Pramipexole (Mirapex): D2
 Roponirole (Requip): D2
 Apomorphine
 Adverse effects: N, D
Anticholinergic Drugs
 Balance between DA and cholinergics (Ach)
 Agents
 Benztropine (Congentin)
 Trihexyphenidyl (Artane)
 Atropine
 Relieve tremor
Amantadine (Symmetrel)


Rapid onset, but short duration. Most start with this.
Causes release of dopamine from storage in the brain. The exact
mechanism is not known.
 An antiviral (prevent A2 influenza) that has an antiparkinsonism
effect.
o Inhibitors of monoamine oxidase B
 Decrease DA metabolism/breakdown, enhancing and prolonging
its effects.
 Selegiline (Eldepryl)
 Inhibits the catabolism of DA in the CNS
 Delays need for levodopa
o Inhibitors of catechol-O-methyl transferase (COMT)
 COMT increases the levels of 3-methyldopa, which in turn
competes with levodopa for an activecarrier mechanism that
governs its transport across the intestinal mucosa and the bloodbrain barrier. Thus, CCOMT inhibitors are used as adjunctive
therapy for parkinsonism patients using levodopa.
 Agents
 Tolcapone (Tasmar)
 Entacapone (Comtan)
 Mechanism: prolongation of plasma half-life of levodopa
 Adverse effects
 Diarrhea
 Bright yellow discoloration of the urine
 Increased toxicity of levodopa
o Acetylcholine-blocking drugs
 There are few anti-muscarinic drugs that reduce the remor and
rigidity of Parkinsonism, but have little effect on the bradykinesia.
Antihyperlipidemic Drugs
 Kinetics of Cholesterol
o Sources
 Diet (0-1000mg/day)- Main source
 Synthesis, chiefly in the liver (600-1000 mg/day); rate-limiting
step is conversion of 3-hydroxy-3-methyl-glutaryl-coenzyme A
(HMG-CoA) to mevalonic acid
o Enters the liver from the GI tract (portal vein) and from the systemic
circulation (hepatic artery)
 Liver also metabolizes fatty acids and lipoproteins; some
catabolism of cholesterol, fatty acid and lipoproteins take place in
GI tissues
 Some cholesterol becomes incorporated into lipoproteins (VLDL,
LDL, IDL, HDL) for transport in plasma.



Most catabolism (to bile acids) occurs in the liver; hepatic LDL
receptor density (on cell surfaces) depends upon plasma LDL
concentration
 Some cholesterol (750-1250 mg/day) and bile acid leaves the liver
via bile.
 About 50% of cholesterol in bile is reabsorbed from the GI tract.
o Absorbed by other tissues to be converted to steroid hormones or to
synthesize membrane material (90% of body cholesterol is in cell
membranes)
o Decreased LDL and increased HDL are both associated with a decrease in
coronary artery diseases.
Bile Acid Sequestrants (decrease plasma cholesterol)
o Agents
 Cholestyramine (Questran)
 Colestipol (Colestid)
o Mechanism: sequestration of bile acids in the intestine. Impairs absorption
of cholesterol in intestine.
 An ion exchange process
 Decreased free bile acid content in the gut decreases cholesterol
absorption
 Decrease reabsorption of bile acids
 Increase catabolism of cholesterol to bile acids.
 Increase cholesterol synthesis, which increases concentration of
LDL receptors on hepatic cells.
 Bile acids absorb cholesterol.
 Without this, cholesterol just circulates (enterohepatic circulation)
and gets caught in the heart, etc.
 Chelation treatment: supposed to decrease plaque in the blood
vessels, but it doesn’t.
o LDL decreases 30%. No effect on HDL
o Adverse effects
 Gritty texture is unpleasant
 GI problems: gas, constipation, nausea
 Decreased GI absorption of several other drugs and drug
interactions (thyroid hormones)
Inhibitors of Cholesterol Synthesis- interferes with rate limiting step
o Agents
 Lovastatin (Mevacor)
 Prevents synthesis of mevalonic acid, a cholesterol
intermediate.
 Pravastatin (Pravachol)
 Simnastatin (Zocor)
 Atorvastatin (Lipitor)
o Mechanism: Inhibition of HMG-CoA reductase
 Drugs resemble HMG-CoA




Decreased concentration of cholesterol in hepatic cells results in
increased synthesis of hepatic receptors in LDL; this decreases
plasma LDL, which results in increased plasma HDL (less MI risk)
o Adverse effects
 Increases serum transaminase (hepatic damage?)
 GI distress: constipation or diarrhea; nausea, gas
Fibric Acid Derivatives
o Agents
 Gemfibrozil (Lopid)
 Clofibrate (Atromid-S)
o Actions
 Increased catabolism of VLDL; this forms additional IDL, which
may be converted to LDL.
 Increased formation of HDL
 Increased or decreased plasma concentrations of LDL
 Increased HDL in plasma
o Mechanisms
 Increased extrahepatic lipoprotein lipase activity (increased VLDL
 IDL)
 Increased cholesterol secretion into the bile
Probucol (Lorelco)
o Mechanisms
 Increases synthesis of extrahepatic Apo E messenger RNA; this
increases Apo E synthesis increased Apo E accelerated movement
of cholesterol to the liver, hepatic catabolism of cholesterol, and
secretion of cholesterol into the bile.
 May inhibit the formation of cholesteryl esters within LDL
particles.
o Actions
 Decrease in LDL
 Decrease in HDL
o Adverse Effects
 NVD
 Prolongation of Q-T interval
Niacin (Nicotinic Acid)
o Small reduction in plasma cholesterol
o Mechanisms
 Decreases release of fatty acids from storage sites, and hepatic
uptake of free fatty acids. Decreased hepatic uptake of free fatty
acids.
 Decreases VLDL synthesis
 Increases clearance of VLDL and chylomicrons from plasma
 Increases VLDL catabolism
o Adverse effects
 Flushing and itching (prevent with 5g of aspirin 1hr prior to niacin)
 Orthostatic hypotension (light headedness)




NVD
Neomycin
o Mechanism unknown
o Adverse effects
 Diarrhea
 Steatorrhea- loss of fat through intestines  dehydration
 Deafness
 Impaired renal function
Sitosterol
o Mechanism unknown.
o Relative to some male sex hormones
Dietary Measures to Decrease Plasma Cholesterol
o Decreased caloric intake
o Decrease saturated fatty acid intake
o Increase intake of soluble fiber, e.g. oat bran
o Due to B-glucan (same mechanism as cholestyramine)