Pharmacology Basics Flashcards

A patient stabilized on warfarin begins taking rifampin for tuberculosis. Two weeks later, her INR drops from 2.5 to 1.2. Which pharmacokinetic mechanism BEST explains this interaction?

Answer: Rifampin induces hepatic CYP enzymes and P-glycoprotein, increasing warfarin clearance

Rifampin is a potent inducer of multiple CYP450 isoforms (especially CYP2C9, CYP3A4) and P-glycoprotein. This dramatically increases the hepatic metabolism and efflux transport of warfarin, lowering plasma concentrations and reducing anticoagulant effect — reflected by the decreased INR. Induction (not inhibition) is the mechanism, and it requires days to weeks to develop fully.

Which statement MOST accurately describes the pharmacodynamic concept of 'spare receptors'?

Answer: Maximum biological effect can be achieved when only a fraction of the total receptor population is occupied

Spare receptors (also called receptor reserve) exist when the maximal tissue response is achieved at agonist concentrations that occupy fewer than 100% of receptors. This means the EC50 for the functional response is lower than the Kd (binding affinity), allowing tissues to respond maximally even when many receptors are blocked. This leftward shift in the E-R curve is the hallmark of spare receptor systems.

A drug has a volume of distribution (Vd) of 350 L/70 kg and is highly lipophilic. A patient takes a massive overdose. Which intervention would be LEAST effective in enhancing elimination?

Answer: Hemodialysis

Hemodialysis efficiently removes drugs that have a small Vd (≤1 L/kg), low protein binding, and high water solubility. A Vd of 350 L/70 kg (5 L/kg) indicates extensive tissue distribution — the vast majority of the drug is sequestered in peripheral compartments, not in the plasma. Dialysis can only clear drug from the plasma compartment, making it ineffective for highly lipophilic drugs with large Vd. Multiple-dose activated charcoal may help by interrupting enterohepatic recycling.

Drug X is a competitive antagonist and Drug Y is a non-competitive (irreversible) antagonist, both acting at the same receptor. How do they DIFFER in their effect on the agonist dose-response curve?

Answer: Drug X shifts the curve right with no change in Emax; Drug Y reduces Emax

A competitive antagonist competes reversibly with the agonist for the same binding site. Increasing agonist concentration can overcome the blockade, so Emax is preserved but the EC50 increases — a rightward parallel shift. A non-competitive (irreversible) antagonist permanently inactivates a portion of receptors. Unless spare receptors are present, this reduces the maximum achievable response (Emax) without a change in the agonist's EC50, because the agonist's potency at remaining receptors is unchanged.

A pharmacist reviews a patient's chart and notes that Drug A has a therapeutic index (TI) of 2 and Drug B has a TI of 15. Which clinical statement is MOST accurate regarding Drug A?

Answer: Drug A has a narrower margin between its effective and toxic doses, necessitating closer monitoring

The therapeutic index is calculated as TD50/ED50 (or LD50/ED50 in animal models). A TI of 2 means the toxic dose is only twice the effective dose — an extremely narrow margin of safety. Even small pharmacokinetic variability (renal impairment, drug interactions, genetic polymorphisms) can push plasma levels into the toxic range. This demands rigorous therapeutic drug monitoring (TDM). TI does not inherently predict half-life or mechanism of toxicity.

A 68-year-old patient with chronic kidney disease (CrCl = 18 mL/min) requires an antibiotic that is 85% renally excreted unchanged. Compared to a patient with normal renal function (CrCl = 110 mL/min), which dosing adjustment strategy is pharmacokinetically MOST appropriate?

Answer: Maintain the same loading dose but increase the dosing interval or reduce the maintenance dose

The loading dose is determined by Vd and target concentration — since renal impairment does not significantly alter Vd, the loading dose remains unchanged (to rapidly achieve therapeutic levels). However, maintenance dosing must be adjusted because the elimination rate constant (ke) is reduced proportionally to CrCl. This is achieved by either extending the dosing interval (τ) or reducing the maintenance dose — or a combination. Reducing the loading dose delays achieving therapeutic concentrations unnecessarily and is a common error.