Pharmacodynamics
Basic Concepts
Essential Terms & Concepts
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law of mass action: application to understanding drug effects
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receptors
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receptor binding
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ligand
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affinity (1/K)
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dissociation constant (K = k2/k1)
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intrinsic activity (efficacy)
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agonist
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antagonist
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competitive (reversible)
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noncompetitive (irreversible)
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partial agonist (cf. mixed agonist/antagonist)
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dose-response analysis
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types
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graded (A50 calculated using linear regression)
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quantal (ED50 calculated using probit analysis)
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compound characterization
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potency
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efficacy
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ED50, ED10, ED100, LD50, TI
(LD50/ED50; cf. use of TI = LD1/ED99
for marketed drugs); also A20, A80, IC50
Receptor Binding Simulations
Ligand Displacement by a Competitive Antagonist
Ligand Displacement by a Noncompetitive Antagonist
Distinguishing Binding Sites from Receptors
Binding sites are not always equivalent to receptor sites. Only binding
sites that are linked with some biological action are considered receptors.
Other tissue sites may bind drug but produce no biological action (e.g.,
lipid and protein binding). Some substances even bind ligands with the
characteristics usually associated only with receptor-binding sites (e.g.,
opioid binding to glass wool fibers). But true receptor binding has several
properties not associated with nonreceptor binding sites. These properties
form the criteria that must all be met to consider a binding site
a true receptor site.
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saturability: binding should plateau with increasing ligand concentrations
indicating that all available receptor-binding sites are occupied
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regional distribution: receptor sites should be found only in tissue
known to contain biologically active receptors for the ligand
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pharmacological specificity: other compounds known to bind with
a given receptor population should displace radiolabeled ligand; also,
binding potencies should correlate with potencies in producing biological
effect, and any stereoselective binding should correspond to a stereoselective
biological effect
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kinetics: dissociation constants from binding data should correspond
with dissociation constants from pharmacological data
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denaturation: most receptors are presumed to be protein; thus exposure
to conditions that denature protein (e.g., boiling, high pH) should destroy
binding
Copyright 1999 Michael A. Bozarth
This page was last updated 04 November 1999 03:29 EDT
Report technical problems to: bozarth@buffalo.edu