PHRD5915 Drug Design Lecture 10 - Pharmacodynamics

prevents agonist from binding to the receptor

parietal cells

nerve terminals

smooth muscle

post ganglionic cell bodies

skeletal muscle cells

receptor is activated as long is it is occupied by the agonist

frequency of interaction between agonist & R dictates R activation (in freq -> inc response)

inactive

• 1) other membrane-assoc'd proteins
• 2) agents binding at other sites on the R
• 3) intracellular proteins (eg G-proteins)

non-competitive antagonist

DON'T

spare receptors

• 1) inhibition of biosynthetic/degradative enzymes
• 2) binding agents

cholinesterase inhibitor decreases ACh metabolism to inc cholinergic responses

binds cholesterol to decrease GI absorption

binds steroidal paralytic agents to inc speed of recovery from paralysis

receptor desensitization

• 1) R number
• 2) R-effector coupling

repeated exposure to a drug leads to increased induction of metabolic enzymes

repeated exposure to drug leads to change in signal transduction pathways or other adaptive responses (reduced responsiveness)

the effect of 2 drugs is equal to the sum of the individual effects (eg alcohol & barbituates)

the effect of 2 drugs is greater than the sum of their individual effects (eg sulfamethoxazol & trimethoprim)

a drug which alone has not effect enhances the potency of a drug which does not have an effect (eg penicillin & probenecid)

effect of one agonist opposes the effect of another agonist (on different tissues)

dose of drug at which 50% of individuals demonstrate the desired therapeutic effect

• 1) clinical potency
• 2) therapeutic selectivity

dose of drug causing deaht in 50% of subjects

provides an estimate of the margin of safety (inc TI -> inc margin of safety)

effect of one agonist opposes the effect of another agonist on different tissues