Pharmacology Basics Flashcards

A patient taking phenelzine (an irreversible MAO inhibitor) for depression requires a new analgesic. Which of the following combinations poses the greatest risk of serotonin syndrome?

Answer: Meperidine + phenelzine

Meperidine (pethidine) is a weak serotonin reuptake inhibitor in addition to its opioid agonist activity. When combined with an irreversible MAOI like phenelzine, it can precipitate a life-threatening serotonin syndrome characterized by hyperthermia, agitation, rigidity, and autonomic instability. Pure mu-agonists like morphine, codeine, and hydromorphone carry substantially lower serotonin syndrome risk with MAOIs, though they are still used cautiously.

A drug has a volume of distribution (Vd) of 700 L in a 70 kg adult. Which statement BEST describes this drug's behavior?

Answer: The drug is extensively distributed into peripheral tissues

A Vd of 700 L far exceeds total body water (~42 L) or plasma volume (~3 L), indicating extensive distribution into peripheral tissues—often due to high lipophilicity or strong binding to tissue proteins. This is not a reflection of renal clearance rate, which is determined by clearance (CL), not Vd. Drugs confined to plasma have small Vd (~3–5 L), and high plasma protein binding with low lipophilicity produces a low Vd, not a high one.

Which mechanism BEST explains why grapefruit juice significantly increases oral bioavailability of felodipine?

Answer: Grapefruit juice irreversibly inhibits CYP3A4 in the intestinal wall

Furanocoumarins in grapefruit juice are mechanism-based (irreversible) inhibitors of CYP3A4 located in enterocytes of the intestinal wall. This reduces first-pass metabolism of felodipine before it reaches the systemic circulation, markedly increasing bioavailability. The effect is on intestinal (not hepatic) CYP3A4. While grapefruit does have some P-gp inhibitory activity, the dominant and clinically defining interaction for felodipine is CYP3A4 inhibition at the gut wall.

A competitive antagonist is added to a system where an agonist produces a dose-response curve. Which quantitative change is MOST characteristic of a competitive antagonist at a fixed concentration?

Answer: Rightward shift in the dose-response curve with unchanged Emax

A competitive (surmountable) antagonist competes reversibly with the agonist at the same receptor binding site. At a fixed antagonist concentration, the agonist dose-response curve shifts to the right (higher EC50), reflecting reduced potency, but the maximum response (Emax) remains achievable if enough agonist is present. This distinguishes competitive antagonism from non-competitive or irreversible antagonism, which depresses Emax. A leftward shift would indicate sensitization or a positive allosteric modulator.

A renally impaired patient (CrCl 20 mL/min) is receiving a drug that is 90% renally excreted unchanged and has a narrow therapeutic index. The prescriber wants to maintain the same average steady-state plasma concentration as in a patient with normal renal function. Which dosing adjustment strategy is MOST appropriate?

Answer: Both A and B are equivalent strategies for maintaining average steady-state concentration

For a drug with linear kinetics, average steady-state concentration (Css,avg) is determined by the ratio of dose to dosing interval (dose rate = F × Dose/τ). Both reducing the dose to 20% at the same interval OR extending the interval by 5-fold (keeping the same dose) will yield the same average Css, since both reduce the dose rate proportionally. For narrow therapeutic index drugs, the choice between strategies depends on whether peak-trough fluctuations matter clinically; however, the question asks only about maintaining average Css, making both options mathematically equivalent.

Which pharmacokinetic phenomenon BEST explains why a patient who has been stable on warfarin for months develops supratherapeutic INRs after starting rifampin, then dangerous subtherapeutic INRs when rifampin is discontinued 3 weeks later?

Answer: Rifampin induces CYP2C9/CYP3A4, requiring warfarin dose increases; discontinuation causes enzyme de-induction lag leading to relative warfarin excess

Rifampin is a potent inducer of CYP2C9 and CYP3A4 (via PXR/CAR nuclear receptor activation). Upon initiation, enzyme induction develops over 1–2 weeks, increasing warfarin metabolism and reducing plasma levels—requiring higher warfarin doses to maintain therapeutic INR. When rifampin is stopped, the induced enzyme mass degrades with a half-life of days to weeks (enzyme de-induction lag). If the warfarin dose was increased to compensate and not promptly reduced upon rifampin discontinuation, falling CYP activity leads to warfarin accumulation and supratherapeutic anticoagulation. The scenario described—supratherapeutic INR after stopping rifampin—reflects this de-induction lag, not inhibition.