Pharmacodynamic Mechanisms Flashcards

The therapeutic index (TI) is calculated as:

Answer: LD50 / ED50

TI = LD50 / ED50; a larger ratio indicates a wider margin of safety between effective and lethal doses.

Allosteric modulators differ from orthosteric ligands because they:

Answer: Bind at a site distinct from the endogenous ligand binding site

Allosteric modulators bind to a topographically distinct site and alter receptor conformation to enhance or inhibit endogenous agonist activity.

Which mechanism best explains the action of aspirin as an irreversible inhibitor of cyclooxygenase?

Answer: Covalent acetylation of a serine residue

Aspirin covalently acetylates Ser530 of COX-1 and Ser516 of COX-2, permanently inactivating the enzyme for its lifespan.

A patient's response to a drug increases rather than decreases with repeated administration. This is best described as:

Answer: Sensitization (reverse tolerance)

Sensitization refers to an augmented response following repeated drug exposure, seen with stimulants like cocaine and amphetamines.

Which receptor family primarily signals through G-protein–mediated second messenger cascades?

Answer: G-protein–coupled receptors (GPCRs)

GPCRs (7-TM receptors) couple to heterotrimeric G-proteins that modulate intracellular effectors such as adenylyl cyclase and phospholipase C.

The concept of 'biased agonism' (functional selectivity) refers to:

Answer: A single ligand preferentially activating one downstream pathway over another at the same receptor

Biased agonists stabilize distinct receptor conformations that preferentially couple to G-protein vs. beta-arrestin pathways, enabling therapeutic selectivity.

The Hill coefficient (n) greater than 1 in a dose-response curve indicates:

Answer: Positive cooperativity or multiple binding sites

A Hill coefficient >1 reflects cooperativity where binding of one ligand increases affinity at adjacent sites, steepening the dose-response curve.