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Principles of Drug Action
Principles of Drug Action
I.
safest
most convenient
most economical
d.
patient must be able to swallow
e.
ii.
Parenteral Route
1. technically means besides the intestine
2. clinically used to mean injection through the skin
3. Options
Subcutaneous (SC)
a.
i. into subcutaneous tissue below epidermis
and dermis
Intramuscular (IM)
b.
i. into the muscle layer
ii. more gradual effect than IV
Intravenous (IV)
c.
i. into the vein
1. most rapid access to the systemic
circulation
Intradermal
d.
i. into dermis layer of skin
Intraspinal
e.
i. into the vertebral interspace and CSF
Epidural
f.
i. into the epideral space below the dura
Intraperitoneal
g.
i. into the peritoneal space
iii. Transdermal Route
1. the drug is absorbed through the skin into the systemic
circulation
2. provides continuous drug delivery to the systemic
circulation
3. less fluctuation is plasma drug levels
iv. Inhalation Route
1. The delivery of gas or aerosol to the airways
systemic effect
a.
i. anesthesia gases
local effect
b.
i. aerosol for bronchodilation
2. Advantages
Smaller doses
a.
More rapid onset
b.
Decreased systemic side effects
c.
Convenient and easily tolerated
d.
3. Disadvantages
b.
c.
b.
Enteral
Parenteral
tablet
capsule
suppository
solution
suspension
depot
elixir
suspension
II.
Inhalatio
n
gas
aerosol
Transdermal
patch
paste
Topical
Skin
powder
lotion
ointment
Topical
Mucous Membrane
lozenges
sublingual tablets
ophthalmic, nasal,
and otic solutions
cream
3. Inhalation Route
Lower Respiratory Tract
a.
i. Airway surface liquid
ii. Epithelial cells
iii. Basement membrane
iv. Interstitium
v. Capillary vascular network
vi. Smooth muscle or glands of the airway
4. Methods by which drugs move across membrane
barriers
Aqueous diffusion
a.
i. Occurs in interstitial spaces and within cells
ii. Transport across epithelial linings is
restricted due to small pore size
iii. Capillaries have larger pores that allow
passage of most drug molecules
iv. Diffusion is by a concentration gradient
Lipid diffusion
b.
i. A drug must be lipid-soluble in order to
diffuse across the lipid membranes of the
epithelial cells
Carrier-mediated transport
c.
i. Carrier molecules can transport drugs that
are similar to the substances they normally
transport
Pinocytosis
d.
i. the process of membrane engulfment and
transport of a substance (drug) into the cell
in vesicles
5. Factors Affecting Absorption
Route of administration
a.
i. determines which barriers to absorption that
must be crossed by a drug
ii. determines the drugs time to onset and
peak effect
1. IV route provides a very rapid onset
and peak effect
Blood flow to the site of absorption
b.
i. Adequate flood flow is essential for optimal
absorption
ii. Distribution
1. To be effective at its desired site of action, a drug must
have a certain concentration.
2. Concentration is partially determined by the rate of
Amoxicillin
Azithromycin
Digoxin
Gabapentin
Morphine
Paroxetine
Terbutaline
1.7
40
39
6.5
1.9
17
14
6. Time-Plasma Curves
the concentration of a drug in the plasma over
a.
time
can indicate if the dose given is sufficient to reach
b.
and maintain a critical threshold of concentration
in the bodily fluid (usually blood) needed for
therapeutic effect in the body
C. The Pharmacokinetics of Inhaled Aerosol Drugs
i. The inhalation route together with the physical/chemical
nature of the drug will determine the absorption, distribution,
metabolism, and elimination of the aerosol drug
ii. Local effect
1. nasally inhaled vasoconstricting agents (decongestant)
Afrin
a.
2. inhaled bronchodilator
albuterol
a.
i. Proventil
ii. Ventolin
iii. Systemic effect
1. inhaled treatment for influenza
zanamivir (Relenza)
a.
2. inhaled treatment for pain control
morphine
a.
3. inhaled insulin for control of diabetes
iv. Inhaled Aerosols in Pulmonary Disease
1. intended for a local, targeted effect in the lung and
airway
2. used to maximize lung deposition while minimizing
systemic absorption and side effects
3. results in higher drug concentrations in the target organ
(lung)
v. Distribution of Inhaled Aerosols
1. Oral Portion (Stomach)
A portion of the aerosol impacts in the oropharynx
a.
and is swallowed (90%)
III.
Structure
Pharmacokinetics
Side Effect
Isoproterenol
Catecholamine
Peak effect: 20 minutes
Duration: 1.5-2 hours
Increased heart rate
Albuterol
Saligenin
Peak effect: 30-60 min.
Duration: 4-6 hours
Little/no change in heart rate
Class of drug
Therapeutic effect
Adrenergic bronchodilator
Relax airway smooth muscle
Adrenergic bronchodilator
Relax airway smooth muscle
elicited
3. The lower the ED50 for a given drug, the more potent
the drug is
v. Therapeutic Index
1. Calculation
LD50
a.
i. The dose of a drug lethal to 50% of the test
population (animal)
ED50
b.
i. The dose of a drug effective for 50% of the
test population
TI = LD50/ED50
c.
2. Represents the safety margin of a drug
3. The smaller the TI, the greater the risk of going from a
therapeutic effect to a toxic effect
4. Example of drugs with narrow TI
Theophylline
a.
Digitalis
b.
5. Example of drug with wide TI
Penicillin
a.
vi. Terms related to pharmacodynamics
1. drug affinity
the tendency of a drug to combine with a receptor
a.
may be on cell surface, in cell or with enzyme
b.
2. drug efficacy
the tendency of a drug-receptor complex to cause
a.
a specific response
3. agonist
a drug that binds to a receptor (has affinity) and
a.
initiates a response (has efficacy)
4. antagonist
a drug that binds to a receptor (has affinity) but
a.
causes no response (has no efficacy)
vii. Drug Interactions
1. antagonism
two drugs with opposing effects
a.
one drug counteracts the other drug by:
b.
i. inactivating the drug
ii. the two effects of the drugs cancel each
other
iii. one drug blocks another from binding to
and activating the receptor
2. synergism
occurs when two drugs act on a target organ by
a.
Pharmacogenetics
A. Definition: The study of heredity or genetic differences in an
individuals response to a drug
B. Genetic differences affecting drug metabolism have been most
extensively studied
C. Example: succinylcholine
i. A paralyzing agent used during surgery and endotracheal
intubation
ii. Duration of action is usually minutes
iii. In approximately 1 in 3000 individuals, it may take several
hours to recover from the drug and begin to breathe
spontaneously
1. mechanical ventilation will be required until
spontaneous breathing is adequate