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- Area of pharmacology concerned with the Drug Size and Molecular Weight (MW)
undesirable effects of chemicals on biologic
- Vary in size
systems
MW 7 (lithium)
Pharmacogenomics MW 50,000 (thrombolytic agents)
- Majority have MW between 100 and 1000
- Finds the exact mechanism of action of drugs
- 100 MW
- Identifies the receptors
For selective binding
- 1000 MW
For traversing to different barriers of - Strongest
the body - Irreversible
- >1000 MW
ELECTROSTATIC BONDS
Cannot move within the body
Given directly at the site of action - More common
- Weaker
Drug Shape
- Eg, between cation and an anion GENERAL
- Chirality PRINCIPLES OF
Stereoisomerism
HYDROPHOBIC BONDS
Exist as enantiomeric pairs
o Carvedilol - Weakest
(S)(-) isomer, potent beta receptor - Highly lipid soluble drugs
blocker
(R)(+) isomer weak beta receptor Drug - Body Interactions
blocker
- PHARMACODYNAMICS
o Ketamine
- PHARMAKOKINETICS
(+) more potent anesthetic and less
toxic than the (-) PHARMACODYNAMIC PRINCIPLES
Racemic mixture
- Drug (D) + receptor-effector (R) → drug-
receptor-effector complex → effect
- D + R → drug-receptor complex → effector
Lock and key mechanism
molecule → effect
- D + R → D-R complex → activation of coupling
molecule → effector molecule → effect
- Inhibition of metabolism of endogenous
activator → increased activator action on an
effector molecule → increased effect
PHARMACODYNAMICS
- Constitutive activity
Some of the receptor pool must exist in
Ra form
May produce same physiologic effect as
agonist-induced activity
Occurs in the absence of the agonist
- Agonist-binds to and activate the receptor
Drug Receptor Bonds Full agonist
o Activates receptor-effector
- Chemical forces or bonds through which the
system to the maximum
drug interacts with the receptors
extent (Ra-D pool){activated
- Weaker bonds are more selective bonds
form}
Drug Receptor Bonds Partial agonist
o Binds to the same receptors
COVALENT BONDS and activate them in the
same way but do not evoke - A model of drug-receptor interaction. The
as great a response receptor is able to assume two conformations.
- Allosteric modulators In the Ri conformation, it is inactive and
Binds to a site on the receptor produces no effect, even when combined with a
molecule separate from the agonist drug molecule. In the Ra conformation, the
binding site receptor can activate downstream mechanisms
Modifies receptor activity without that produce a small observable effect, even in
blocking agonist activity the absence of drug (constitutive activity). In
May increase or decrease response to the absence of drugs, the two isoforms are in
agonist equilibrium, and the Ri form is favored.
Noncompetitive Conventional full agonist drugs have a much
- Inverse agonist higher affinity for the Ra conformation, and
Drug has a stronger affinity for the Ri mass action thus favors the formation of the
pool (nonfunctional form) Ra–D complex with a much larger observed
Reduces constitutive activity effect. Partial agonists have an intermediate
Results in effects that are opposite of affinity for both Ri and Ra forms. Conventional
the effects produced by conventional antagonists, according to this hypothesis, have
agonists equal affinity for both receptor forms and
- Antagonist maintain the same level of constitutive activity.
Binds to a receptor, compete with Inverse agonists, on the other hand, have a
and prevent binding by other much higher affinity for the Ri form, reduce
molecules constitutive activity, and may produce a
contrasting physiologic result.
PHARMACOKINETICS
- Prodrug
Inactive precursor
Must be administered and
converted to the active drug by
biologic process inside the body
Absorption
Distribution
Metabolism
Elimination
WEAK BASE
WEAK ACID