Introduction to pharmacodynamics

===Lecture Details===
Wayne Hodgson; Week 4 MED1011; Pharmacology
===Lecture Content===
After drug has bound to receptor, transduction mechanism binds to cause cellular effect. The more receptor sites occupied by drugs, the greater the response. Clark's model is the magnitude of the response is proportional to DR complex (E wiggly symbol [DR]), maximal response occurs when all receptors are occupied ([Rt] wiggly Emax)
Concentration of free receptor sites is equal to the amount of receptor sites minus that bound to drug molecules [R] = [Rt] - [DR]
Stephenson said drug could produce maximal effect before binding all receptors, efficacy (NMJ 30 million receptors, 40k needed for response). If a full agonist needs 5% of receptors there is a receptor reserve of 95%. Partial agonists have affinity, have efficacy but lower than that of a full agonist (produce less efficacy when binding same amount of receptors as a full agonist). EC50 is the agonist concentration that produces 50% of maximal response, is a measure of potency. pD2 is derived from -logEC50.
Drug antagonism can be chemical, physiological, pharmacokinetic, pharmacodynamic. Antagonists have no efficacy. Competitive antagonism is surmountable, has parallel shifts in log CR curves. Irreversible antagonism is insurmountable, at high concentrations of antagonist there is depression of maximum.
Antagonist potency (pA2) is negative log of the antagonist concentration in which it is necessary to double the agonist concentration to produce the same effect. This determination is only relevant for competitive antagonists. Compares potency of two antagonists.
Inverse agonists reduce the level of activation of a receptor, particularly important at G-protein receptors (agonist dependant). Antihistamines are inverse agonists.
===Readings===