Routes of
Administration
• Enteral- gastrointestinal tract
absorption (po): oral
• Parenteral- by injection (iv, sc,
im)
• Iv has benefits and
disadvantages
• 1-No barrier to absorption,
• 2-rapid onset,
• 3- use of large fluid volumes,
4-use of irritant drugs
1
Must go thru GI system first
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Factors which influence:
•Concentration
•Lipid/water solubility
•Ionization (difficult to cross lipid
membrane)
•Acidity (ionize in opposite pH)
•Contents/movement of GI
enzymes
pH 1.2
pH2-6.6
drug
pH7.4
STOMACH
Blood circulates around
entire body 1/min
SMALL
INTESTINE
1st -pass
metabolism
LIVER
• Pills Must Dissolve/Breakdown
• Most Absorbed in Small Intestine
• compressed tablet (must be “scored” to divide)
Advantages to oral administration
1- Easy, convenient, inexpensive (relatively)
2-No risk of fluid overload, infection or embolism
3-Can potentially be reversed if overdosed
4- Emesis- vomiting -Catharsis- rapid emptying of small intestine and
bowel before absorption (activated charcoal absorbs drugs)
• Disadvantages
1– Variability of absorption (young vs old) (empty vs full stomach),
pH
2– Inactivation by proteases and acid
3– Can’t be given to comatose patients or noncooperative patients
(will not swallow pills?)
4- Inflammation of GI tract and irritation
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Introduction
Oral
• Absorbed from stomach or intestine
• Must get through epithelial cell barrier and capillary wall
• Must pass through cells, not between them
Factors that determine rate of absorption
•
•
•
•
•
•
1- Solubility and stability (to acid & proteases)
2- Gastric and intestinal pH
3- Gastric emptying time
4- Food in the gut
5-Co-administration of other drugs
6-Capsule (coating) around drug
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Introduction
“Packages” for Oral administration:
• Tablets
•
•
•
•
– Enteric coatings
– Sustained release preparations
Chemical equivalenceif drug contains the same amount of the identical chemical
compound
• Bioavailability- if drug is absorbed at the same rate and to
the same extent
• Two formulations of the same drug may be chemically equivalent
but differ in bioavialability
Tablets• Mixture of a drug plus binders and fillers compressed together. If
made by different companies can differ in rates of disintegration
and dissolution (availability)
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Introduction
Enteric-Coated Preparations• Drugs covered with material designed to dissolve in the intestine
but not in the stomach (composed of fatty acids, shellac, waxes
(protect from acid and pepsin and protect stomach from adverse
effects)
Sustained-release• – Capsules filled with tiny spheres that contain drug. Spheres have
coatings that dissolve at variable rates.
• Drug is released at steady rate over number of hours
Other ways to deliver drugs• Topical- local therapy: skin, eyes, ….
• Transdermal patches- nicotine, ….
Inhalation- asthma, oxygen, ….
Rectal/vaginal suppositories- local and systemic effects
Nursing Pharmacolog -Azza Awad
8
Direct
4/24/2015 injection into specific tissue/organ- CNS, heart
Introduction
Sustained Release Oral
•
•
•
•
•
Do Not Break
Enteric Coated
Beads or Granules
Matrix i.e. Slow K
Repeat action i.e.
Chlor-Trimetron
• Osmotic Pump i.e.
Acutrim
Sublingual / Buccal
• Rapid absorption and response
• Highly vascular areas
• Avoids “First Liver Bypass”
Indications for parenteral injections:
• 1– Emergencies (quick response to drug required)
• 2– When drugs would be destroyed by pH or
enzymes
• 3– When drugs would not be absorbed through
membranes
• 4– Drugs that might cause severe local injury if
administered orally or topically
• 5– For patients who cannot or will not take oral
medication
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Introduction
Injection
• Intravenous (IV) - intra = “within”, vena = “vein”
• Intramuscular (IM) - muscle
• Subcutaneous (SC) - under skin
• Intraperitoneal (IP) - abdominal cavity
• Intracranial (IC) - brain
IV
PRO’s
• Fast (dispersed equally ~
1min)
• Dose readily controlled
• Blood levels remain steady
CONS
• DANGEROUS! Drug can’t
be recalled!
• Contamination/infection
• Clogged blood vessel if
drugs insoluble or comes out
of solution
Intramuscular
• Only barrier to absorption is capillary wall
• Rate of absorption can be fast or slow determined by;
•
–Solubility of drug
•
–Blood flow to site of injection
Poorly soluble drugs can be administered in this manner- can be
dissolved as blood flow goes by
Can be used to have drug absorbed gradually over time (adjuvant
therapy– injection in thick bolus)
• Drawbacks to IM injection are
• –Discomfort (painful) and inconvenience (not as easy as oral
admin)
• Subcutaneous
• – sc similar to im administration
Nursing Pharmacolog -Azza Awad
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Introduction
THE REST
• IM. - slow even absorption
• SC - absorption depends on blood flow to
site. Hormones often in pellets.
• IP - rapid, even absorption. Risk of
infection & puncture of organ. Painful.
• IC - rarely used in humans, too risky
Transdermal
• Thru the skin
• Must be lipid soluble
• Even, slow rate of
absorption
– Nicotine patches
– Motion sickness patches
• Some compounds can
poison thru the skin
(malathion)
Rectal
• Advantages
– nausea, NPO, difficulty swallowing
– avoids first liver bypass
• Disadvantages
– May be erratic absorption
– May cause irritation
CON’S
Inhalation
•
•
PRO’s
Rapid onset Absorption
immediate because capillary
walls of lungs exposed
Speedy route: lungs-heart-brain
•
Once drug source removed, no
additional drug enters body
•
•
No 1st pass metabolism
Volatile gases - diffuse in and
out of blood (anesthetic, nitrous
oxide)
•
•
•
•
•
FAST, DANDGEROUS
Dosing can be difficult (lung capacity)
Irritants - pneumonia
Not much known about long term
effects of particulate matter - cause
membrane damage (Tar paves lungs)
Smoking (marijuana, opium, cocaine) smokeborne particles dissolve on
membrane & diffuse thru capillary
walls, don’t diffuse out of lungs
Mucous Membranes
• Mouth, nose, eye, rectum, vagina
• Some drugs readily absorbed
(cocaine, amphetamine), most are not.
Factors Affecting Absorption & Distribution
Solubility
– lipid cross membranes, if not, H2O-filled pores
– ionization
• polar substances dissolve/ionize in water
• pH-acids ionize in alkaline & visa versa
Tissue Affinity
-protein binding ( ex. Albumin)
Membrane Barriers - capillary, cell, BBB, placental
– Membrane transport
Time Course of Drug Responses
Must regulate
• Time at which drug responses start
• Time they are most intense
• Time they cease
• The four pharmacokinetic processes– absorption,
distribution, metabolism, and excretion–
determine how much drug will be at it sites of
action at any given time
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Introduction
Plasma levels of drug
Can be measured and adjusted up or down by
changing dosage, the timing of administration, or
both
Concentration at site of action most important, not
plasma level, but it is not possible to measure drug
levels at site of action. There is a DIRECT
correlation between plasma levels and levels at
site of action
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Introduction
Onset, Peak, and Duration
Onset
• The time it takes for the drug to elicit a
therapeutic response
Peak
• The time it takes for a drug to reach its maximum
therapeutic response
Duration
• The time a drug concentration is sufficient to
elicit a therapeutic response
Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc.
Therapeutic Drug Monitoring
Peak Level
• Highest blood level
Trough Level
• Lowest blood level
Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc.
Monitoring
• The effectiveness of the drug therapy must be
evaluated
• One must be familiar with the drug’s:
– Intended therapeutic action (beneficial)
– Unintended but potential adverse effects
(predictable, adverse reactions)
Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc.
Monitoring (cont’d)
•
•
•
•
•
•
Therapeutic index
Drug concentration
Patient’s condition
Tolerance and dependence
Interactions
Adverse drug effects
Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc.
Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc.
Minimum Effective Concentration
• MEC is the plasma drug level below which therapeutic
effects will not occur (drug must be present at or above
MEC to be effective)
• Toxic Concentration
• Occurs when plasma level of drug gets too high
• Therapeutic Range
• Range of drug concentrations falling between MEC and
toxic concentration that is the therapeutic range. Must
maintain concentration of drug within therapeutic range
to be most effective. Width of therapeutic range
important (the larger, the easier to maintain between)
29
• Multiple doses maintain a steady level of drug in
system at a plateau (steady level): the amount of
drug given is equal to the amount of drug
eliminated
• When a drug is administered repeatedly in the
same dose, plateau will be reached in
approximately four ½ lives
• The degree of fluctuation that can be tolerated,
from one dose to another, depends upon the
drug’s therapeutic range
• Can limit fluctuations by continuous infusion
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Introduction
Monitoring (cont’d)
• Therapeutic index
– The ratio between a drug’s therapeutic
benefits and its toxic effects
Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc.
Effective and Lethal Dosage
• ED50 - dose that has desired effect in 50% of
subjects
• LD50 - lethal dose for 50%
• Therapeutic Index - index of relative safety;
ratio of LD50/ ED50 (higher=better)
– 20 = relatively safe
– 100 = preferred
6. Therapeutic Index
a. Ratio = LD50 / ED50
- LD50 = Lethal dose in 50% of animals
- ED50 = Effective dose in 50% of animals
b. A good guide to determine & compare SAFETY of drugs
c. The Higher the therapeutic index  The Safer the drug
d. Valid only when dose/response curves for effectiveness & toxicity are
parallel
Therapeutic
Index of
Warfarin vs.
penicillin
Therapeutic Index
•
•
•
•
A measure of a drug’s safety
Defined as the ratio of a drugs LD50 to its ED50
LD50 is the dose that is lethal to 50% of the animals treated
A small therapeutic index indicates that a drug is UNSAFE while a
large therapeutic index indicates that the drug is relatively SAFE.
• •LD50/ED50 ratio: if lethal dose is 100mg and the effective dose is
10mg there is a 10X difference and indicates that it should be safe to
take the medication at the 10mg level.
• If a drug is to be deemed SAFE, the highest dose required to produce
therapeutic effects must be substantially LOWER than the lowest
dose capable of causing death
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Monitoring (cont’d)
• Tolerance
– A decreasing response to repeated drug doses
Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc.
Monitoring (cont’d)
• Dependence
– A physiologic or psychological need for a drug
Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc.
Monitoring (cont’d)
Interactions may occur with other drugs or food
• Drug interactions: the alteration of action of
a drug by:
– Other prescribed drugs
– Over-the-counter medications
– Herbal therapies
Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc.
Monitoring (cont’d)
• Drug interactions
–
–
–
–
Additive effect
Synergistic effect
Antagonistic effect
Incompatibility
Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc.
Monitoring (cont’d)

Adverse Drug Events
Medication errors
 Adverse drug reactions

Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc.
Monitoring (cont’d)
Adverse Drug Reactions
•
•
•
•
Pharmacologic reactions, including adverse effects
Hypersensitivity (allergic) reaction
Idiosyncratic reaction
Drug interaction
Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc.
Monitoring (cont’d)
Adverse effects
•
•
•
•
Predictable, well-known reactions that result in
little or no change in patient management
Predictable frequency
Occurrences are related to the size of the dose
Usually resolve when the drug is discontinued
Mosby items and derived items © 2007, 2005, 2002 by Mosby, Inc., an affiliate of Elsevier Inc.
Doses of Drugs (Posology)
1. Therapeutic Dose:
Average dose calculated for
an Adult, Male, 20-60 year
old & 70 Kg body weight.
2. Initial Dose: Initial large
dose aiming to reach the
therapeutic plasma
concentration
3. Maintenance Dose: Small
daily dose required to
replace eliminated drug
from the body to maintain
the achieved therapeutic
plasma concentration.
4. Maximal Tolerated Dose:
Highest dose without toxic
effects
5. Lethal or Fatal Dose: Dose
that kill the patient or an
experimental animal
6. Therapeutic Index: See next
slide
7. Standard Margin of Safety
(SMS):
a. Percentage by which ED99
must be increased to reach
LD1.
b. SMS = [ (LD1/ED99) – 1 ] x 100
c. Useful when dose/response
curves for effectiveness &
toxicity are not parallel.
Factors Affecting The Dose &
Action of Drugs 1
1.
2.
Biological variation Range of dose. Start by minimal effective dose then
increase the dose gradually as needed.
Age Decrease the dose in extremities of age.
A. Geriatrics (Elderly > 60 years):
a. They have exhausted drug-elimination mechanisms (metabolism
& excretion).
b. Use 2/3 or 3/4 of the adult dose.
B. Pediatrics (Young < 12 years):
a. They have immature drug-elimination mechanisms (metabolism
& excretion).
b. Calculate the dose by:
- Infant (< 1 year) dose (Clark’s Formula) = Adult dose X (Weight
of infant in Pounds/150)
- Child (1 – 12 year) dose (Young’s Formula) = Adult dose X [Age
in years / (Age + 12)]
or (Dilling’s Formula) = Adult Dose X (Age in Years / 20)
or = Adult Dose X (wt of child in Kg / 70)
Factors Affecting The Dose &
Action of Drugs 2
3. Body Weight & Surface Area:
a. Skeletal muscle weight is more important than fat or edema.
b. Surface area =  Height in cm X weight in Kg / 3600
c. Surface area is more accurate in calculating doses for children &
infants.
4. Sex:
a. Males need higher doses than females:
 Males have bulky muscle tissue & Androgens (HME Inducers)
 Females have bulky fat tissue & Estrogen (HME Inhibitor)
b. Some drugs are contraindicated in Females during physiological
periods:
 Menstruation: Aspirin & Cathartics   Bleeding
 Pregnancy: Sex hormones, Oxytocics (Ergotamine) & Teratogens
(Phenytoin)
 Labor: Barbiturates & Morphine  Neonatal asphyxia
 Lactation: Drugs excreted in milk eg Purgatives, Tetracyclines &
Chloramphenicol
Factors Affecting The Dose &
Action of Drugs 3
5.
6.
Route & Time Of Administration:
Affect the dose: usually I.V. dose < Oral dose
Affect the effect:
After meal  No effect
Orally  Empty stomach  4 g  Cholagogue
Mg SO4
15 g  Saline purgative
I.V.   CNS,  Smooth, Skeletal & Cardiac muscle
Retention Enema  Dehydrating agent e.g. in brain edema
If drug is irritant  Use after meals
If drug is sedative  Use at bed time
Cumulation:
a.
Occurs with zero-order kinetics when the rate of intake > rate of
elimination.
b. Examples: Digitalis, Aspirin L.D., Phenytoin L.D. & Ethanol L.D.
c.
To avoid cumulation either  The dose or  Frequency of
administration.
Factors Affecting The Dose &
Action of Drugs 4
7. Psychological Effect:
a. Some patients improve by Psychological
(Suggestion) rather than Pharmacological effect of
the drug (Placebo effect).
b. Placebo (Dummy medication) is an inert substance
(Lactose, starch, etc.) used in a dosage form (Tablet,
capsule, etc). Useful in:


Treatment of patients by psychological suggestion
As a comparison when testing new drugs
Factors Affecting The Dose &
Action of Drugs 5
8. Pathological Condition:
a. Some drugs act ONLY in presence of disease:
 Aspirin acts as an antipyretic ONLY in fever
 Digitalis acts as a diuretic ONLY in heart failure
b. Pathology may cause supersensitivity:
 a- Adrenaline in thyrotoxicosis
 b- -Blockers in bronchial asthma
c. Pathology may affect drug kinetics: Achlorhydria   Intrinsic factor  
Absorption of Vit B-12  Pernicious anemia.
d. Liver and/or kidney disease may affect the dose of some drugs.
1. Allergy (Hypersensitivity)  Abnormal response
9. Idiosyncrasy (Pharmacogenetics)  Abnormal response
10. Supersensitivity (Intolerance)   Dose of the drug
11. Tolerance   Dose of the drug
12. Drug interactions  Summation, Synergism, Antagonism &
Reversal.
Dose-Response (D-R) Relationship
• Effectiveness of drug determined by a
D-R curve
• Shows relationship between drug dose
& magnitude of effect
D-R Curve Shows Drug Characteristics
Potency - amount of drug to
achieve a certain effect
Efficacy - dose that produces
maximum effect
Slope - steep slope = small
changes cause big differences in
response.
A drug may be less potent but have a higher efficacy
9
8
Intensity of Effect
7
6
5
4
A
B
3
2
1
10
20
30
40
50
60
Dosage (mg/kg)
70
80
Combined
Effects
Co-administration
of drugs =
combined
effects
– Additive
– Synergistic (2
drugs = bigger
than expected
effect)
– cummulative
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