PH1.1-13 | General Pharmacology Foundations — Practice Quiz

Correct. A large Vd (>300 L) indicates the drug is extensively sequestered in peripheral tissues — typically due to high lipophilicity or binding to tissue proteins. High plasma protein binding actually REDUCES Vd by keeping drug in plasma.

Vd reflects apparent drug distribution. A Vd >> total body water (42 L) indicates extensive tissue binding rather than plasma distribution.

Incorrect. Volume of distribution is NOT the literal anatomical volume. A Vd of 500 L exceeds total body water, indicating the drug leaves the plasma and concentrates in tissues — driven by lipophilicity or tissue binding. High plasma protein binding would constrain the drug to plasma, giving a low Vd.

Correct. Steady state is achieved in 4–5 half-lives. With a half-life of 2 hours, 4×2 = 8 h and 5×2 = 10 h — both within 12 hours, i.e., Day 1.

Steady state is reached after approximately 4–5 half-lives regardless of dose or dosing interval.

Incorrect. Steady state is reached after 4–5 half-lives, regardless of dosing interval. With t½ = 2 h, steady state is reached in 8–10 h — well within Day 1.

Correct. Type B ADRs are bizarre/idiosyncratic — not predictable from pharmacological action and not dose-dependent. Examples include penicillin anaphylaxis and HLA-B*1502-associated carbamazepine Stevens-Johnson syndrome.

The A–E ADR classification: Type A (augmented) = dose-dependent; Type B (bizarre) = idiosyncratic, not dose-dependent, unpredictable, often immunological or pharmacogenetic.

Incorrect. Type B ADRs are NOT dose-dependent and cannot be managed by dose reduction. They are unpredictable, immunological, or pharmacogenetic. Type A reactions (the most common) are dose-dependent and pharmacologically predictable.

Correct. Rifampicin is one of the most potent CYP450 inducers (CYP1A2, CYP2C9, CYP3A4). Induction markedly increases warfarin clearance, requiring dose increases of up to 5–10-fold to maintain therapeutic INR.

Rifampicin is a potent CYP450 inducer. Induction accelerates warfarin metabolism, lowering plasma levels and anticoagulant effect — a clinically dangerous pharmacokinetic interaction.

Incorrect. Rifampicin is a powerful enzyme INDUCER, not inhibitor. Induction increases the rate of warfarin metabolism, reducing plasma levels and anticoagulant effect — reflected in the falling INR.

Correct. This is the classic 'normal creatinine trap.' Elderly patients have reduced muscle mass and therefore produce less creatinine. Even with GFR reduced to 30–40 mL/min, serum creatinine can remain near 1.0 mg/dL. Gentamicin requires dose adjustment for renal function; the Cockcroft-Gault equation must be applied.

The 'normal creatinine trap': elderly patients have reduced muscle mass and therefore produce less creatinine. GFR may be markedly reduced while serum creatinine remains within the reference range. Cockcroft-Gault must be applied.

Incorrect. The key problem is that creatinine is a marker of muscle breakdown — elderly patients produce LESS creatinine due to sarcopenia. Therefore serum creatinine may appear 'normal' even when GFR is significantly impaired. Always calculate eGFR (e.g., Cockcroft-Gault) before prescribing renally-cleared drugs.

Correct. GTN is almost completely destroyed by hepatic first-pass metabolism after oral ingestion. Sublingual administration delivers the drug directly to systemic circulation via the buccal mucosa veins (drain to the superior vena cava, not the portal system), bypassing the liver.

Sublingual, buccal, transdermal, and intravenous routes bypass first-pass metabolism. Glyceryl trinitrate (GTN) undergoes near-complete first-pass metabolism if swallowed, making sublingual delivery essential.

Incorrect. Enteric-coated, extended-release, and gastro-resistant formulations are all designed for oral (and therefore portal venous) delivery — all subject to first-pass hepatic metabolism. Sublingual, buccal, transdermal, rectal, and intravenous routes bypass first-pass metabolism.

Correct. Competitive antagonists bind to the same receptor site as the agonist and shift the dose-response curve to the RIGHT (higher EC50), but the maximum response (Emax) is preserved if the agonist dose is increased sufficiently. This is surmountable antagonism.

Competitive antagonism is reversible and surmountable — increasing agonist concentration can displace the antagonist from the receptor, restoring the full agonist effect. This distinguishes competitive from non-competitive (insurmountable) antagonism.

Incorrect. Competitive antagonism is REVERSIBLE. The antagonist competes with the agonist for the same binding site; raising agonist concentration can displace the antagonist and restore full effect (surmountable). Irreversible blockade characterises non-competitive or allosteric antagonism.

Correct. Regulatory bioequivalence requires that the test product's pharmacokinetic parameters (AUC and Cmax) fall within the 90% confidence interval of 80–125% of the reference product's values. This standard ensures therapeutic equivalence for most drugs.

Bioequivalence is defined by the regulatory criterion that the generic drug's AUC and Cmax fall within 80–125% of the reference (innovator) product under standardised pharmacokinetic study conditions. It does NOT require identical formulation — the active ingredient and dose must be the same.

Incorrect. Bioequivalence does NOT require an identical formulation — excipients may differ. It requires pharmacokinetic equivalence: the 90% confidence interval for AUC and Cmax ratio must lie within 80–125%. This criterion has been validated to ensure therapeutic equivalence.

Correct. 'Probable/Likely' in the WHO-UMC scale requires: reasonable temporal relationship, unlikely due to disease or other drugs, pharmacologically plausible, clinical improvement on withdrawal (dechallenge positive). All criteria are met here. Rechallenge is not needed (and would be unethical for anaphylaxis).

WHO-UMC causality categories: Certain (rechallenge positive), Probable/Likely (reasonable time-sequence, known reaction, plausible — no rechallenge needed), Possible (time-sequence reasonable but confounders exist), Unlikely (time-sequence improbable).

Incorrect. With appropriate timing, a known ADR pattern, pharmacological plausibility, and positive dechallenge (improvement on stopping), this meets the 'Probable/Likely' WHO-UMC criteria. 'Possible' applies when confounding factors exist or the time course is less clear.

Correct. Neonates have proportionally greater total body water and lower plasma albumin, increasing the Vd for hydrophilic drugs like aminoglycosides. Paradoxically, this often requires a HIGHER mg/kg loading dose to achieve therapeutic levels, combined with extended dosing intervals due to reduced renal clearance.

Neonates have ~75–80% total body water (vs ~60% in adults), reduced plasma protein binding (lower albumin), and immature renal and hepatic function. Water-soluble drugs like aminoglycosides have a larger Vd in neonates, requiring higher mg/kg loading doses but less frequent dosing due to reduced clearance.

Incorrect. Neonates have greater total body water (higher Vd for water-soluble drugs), immature CYP450 enzymes (REDUCED first-pass metabolism), and immature renal function (slower clearance — not faster). Lipophilic Vd may indeed be reduced due to less adipose tissue, but aminoglycosides are water-soluble.