Week 2 General Receptor Pharmacology: Antagonism, Inverse Agonism, and Desensitization

Vocabulary flashcards covering key pharmacology concepts including receptor activity, inverse agonism, types of antagonism, dose-response relationships, and cellular mechanisms of desensitization.

Affinity

Describes how tightly a drug binds to a receptor.

Efficacy

Describes the ability of a bound drug to activate a receptor and produce a biological response.

Constitutive activity

The ability of some receptors to display signaling activity and produce a biological response even in the absence of a ligand.

Inverse agonist

A drug that binds to a receptor displaying constitutive activity, shifts the equilibrium toward the inactive state, and decreases baseline receptor activity below baseline.

Neutral antagonist

A drug that has affinity for a receptor but zero intrinsic efficacy, blocking agonist binding without altering baseline or constitutive receptor activity.

Negative efficacy

The property of an inverse agonist to actively shift a receptor toward an inactive state and reduce baseline signaling.

Rimonabant

An inverse agonist at the CB1 cannabinoid receptor developed for obesity but withdrawn due to serious adverse effects including depression, anxiety, and nausea.

Chemical antagonism

A type of antagonism that occurs when two substances directly combine together in solution, reducing the activity of one or both.

Pharmacokinetic antagonism

Antagonism occurring when one drug alters the absorption, distribution, metabolism, or excretion (ADME) of another drug, thereby changing the amount of drug reaching its site of action.

Noncompetitive antagonism

Antagonism where a drug interferes at a point downstream or distinct from the agonist receptor binding site in the response pathway.

Physiological antagonism

Antagonism that occurs when two drugs produce opposing physiological effects on the organ or system level through different receptors or mechanisms.

Competitive receptor antagonism

Antagonism occurring when two or more drugs compete for binding to the exact same site (orthosteric site) on a receptor.

Surmountable antagonism

Antagonism that can be overcome by increasing the concentration of the agonist, a key characteristic of reversible competitive antagonism.

Dose ratio

The ratio by which the agonist concentration must be increased in the presence of an antagonist to restore a given biological response.

Irreversible receptor antagonism

Antagonism in which the antagonist dissociates very slowly or forms a covalent bond with the receptor, permanently removing receptors from the available pool and potentially decreasing maximum response.

Tachyphylaxis

A rapid decrease in drug response that develops over a short timeframe, typically over minutes to hours, following repeated drug administration.

Tolerance

A gradual decrease in drug responsiveness that typically develops over days to weeks, requiring higher doses to achieve the initial therapeutic response.

Resistance

A loss of drug effectiveness usually applied to microorganisms (such as bacteria surviving antibiotics) or cancer cells adapting to survive drug exposure.

Uncoupling

A mechanism of receptor desensitization where the receptor remains present on the cell surface but becomes functionally disconnected from its downstream signaling pathway.

Downregulation

A process of receptor desensitization where receptors are internalized, removed from the cell surface, or degraded, reducing the total number of available receptors.