Drug Receptors and Pharmacodynamics II Flashcards
Partial agonist
occupy the same receptor as full agonist, but bring about less than maximum response even at full dosage levels. These are less efficacious
Full agonist
occupy receptors and bring about a full or maximal response (max response being defined as that produced by the most powerful agonist in that tissue)
Antagonism:
antagonist is a drug that inhibits the action of an agonist but has no effect in the absence of an agonist, divided into receptor and non-receptor antagonists
Pharmacological antagonists (aka: receptor anagonists):
bind to the same receptor as the agonist.
Competitive reversible antagonist:
binds reversible to the active site of receptor, but does not stabilize the conformation change required for receptor activation. Antagonist blocks agonist from binding to its receptor and maintains receptor in inactive conformation. EC50 increases (potency decreases) - Emax unchanged (because agonist concentration can be increased to outcompete the antagonist).
Example of competitive reversible agonist
Metoprolol is competitive reversible antagonist of NE in Beta1 receptors in heart that produces a reduction in heart rate. But increase in endogenous NE during exercise will still –> increased heart rate
Noncompetitive irreversible antagonist:
binds irreversibly (covalently) or pseudo irreversibly (with very high affinity-slow dissociation) to the active site of the receptor. Removes functional receptors from the system, limiting the number of available receptors that can contribute to the response. Noncompetitive because an irreversibly bound active site cannot be outcompeted even at high concentrations). The curve shifts downwards and the maximal efficacy (Emax) of agonist is reduced. No shift on the x-axis.
Noncompetitive Allosteric Antagonist
- Drug binds to different site on the receptor than agonist drug. They do no compete with agonist for receptor binding, but inhibit receptor from responding to agonist, so curve shifts downward, result in a dose-dependent decrease in maximal efficacy (Emax). High concentrations of agonist cannot active the receptor. May see a shift to the right (decrease in apparent potency) if spare receptors available
Non-receptor antagonists
include physiological antagonists that bind to a different receptor and chemical antagonists that bind the agonist molecule directly (do not involve any receptor binding).
Physiological non-receptor antagonists
activates or blocks a distinct receptor that mediates a physiologic response that is opposite to that of activation of the receptor for agonist
chemical non-receptor antagonists
does not involve receptor binding, antagonism occurs via inactivation of agonist itself by modifying it or sequestering it so it is no longer capable of binding to and activating the receptor.
examples of chemical non-receptor antagonists
EDTA chelator, antacid neutralizes stomach acid, osmotic diuretics.
example of a physical non-receptor antagonists
The effect of histamine (via histamine receptors) to produce constriction of bronchiolar smooth muscle and the antagonistic action of epinephrine (via adrenergic receptors) to produce bronchodilation when used in the treatment of anaphylactic shock.
