Week 5 content

Partial agonist

a ligand that binds to a receptor and produces a less than maximal effect at receptor

inverse agonist

a ligand that binds to a receptor and prevents its constitutive activity

orthosteric binding site

• primary binding site on receptor

• endogenous agonists, orthosteric agonists, and orthosteric antagonists (competitive antagonists) bind here

allosteric binding site

• distinct site where drugs can act and influence activity of the receptor

• allosteric agonists and allosteric antagonists (non-competitive antagonists) bind here

positice allosteric modulators (PAMs)

act at allosteric site to enhance receptor activity

negative allosteric modulators (NAMs)

act at allosteric site to inhibit receptor activity

pharmacokinetic drug interactions

one drug alters absorption, distribution, metabolism, or excretion of another

pharmacodynamic interactions

when one drug alters pharmacological effect of another, usually at receptor site

additive effect example

percocet (acetaminophen and hydrocodone)

synergistic effect example

alcohol and benzodiazepins

antagonistic effect

L-Dopa and antipsychotic drugs

tolerance

decrease in drug’s effectiveness

acute tolerance

rapid tolerance occurring within a drug taking episode

tachyphylaxis

rapid tolerance occurring after limited number of drug administrations

metabolic tolerance (pharmacokinetic tolerance)

typically caused by enzyme induction

cellular tolerance (pharmacodynamic tolerance)

• typically caused by changes in the affinity or efficacy of a drug at its receptors (reduced potency)

• main mechanisms responsible for this tolerance are receptor downregulation/upregulation

behavioral tolerance (conditioned tolerance)

tolerance that occurs due to learning and adaptation mechanism; stimuli and drug effects become associated with repeated pairings

sensitization

an increase in a drug’s effectiveness following repeated administration

withdrawal

physiological changes that occur when the use of a drug is stopped or the dosage is decreased (actually or via tolerance)

homeostasis

tendency of physiological system to maintain an equilibrium