Drug Interactions and Adverse Effects Flashcards

A patient on heparin develops a falling platelet count 5–10 days after starting therapy. What complication should the pharmacist suspect?

Answer: Heparin-induced thrombocytopenia type II (HIT) — immune-mediated, with paradoxical thrombosis risk

HIT type II occurs 5–14 days after heparin exposure (or within 24 hours with recent prior heparin exposure). Antibodies against heparin-PF4 complexes activate platelets, causing thrombocytopenia (platelet count fall >50%) and paradoxical thrombosis (venous and arterial). Heparin must be stopped immediately and non-heparin anticoagulation (argatroban, danaparoid) started.

A patient develops lactic acidosis while on metformin. Which condition likely precipitated this adverse effect?

Answer: Acute kidney injury — metformin accumulated due to reduced renal clearance

Metformin is renally excreted unchanged. Acute kidney injury (AKI) or conditions reducing GFR (dehydration, contrast media, sepsis, surgery) cause metformin accumulation, increasing the risk of lactic acidosis by inhibiting hepatic lactate metabolism. Metformin should be held during illness and before contrast procedures.

A patient on ciprofloxacin reports muscle weakness and difficulty climbing stairs. Ciprofloxacin levels are unexpectedly high. What interaction is responsible?

Answer: Ciprofloxacin inhibits CYP1A2, increasing theophylline levels — wait, this patient has elevated ciprofloxacin due to reduced renal clearance in the setting of reduced GFR

Ciprofloxacin (and fluoroquinolones generally) are partially renally excreted. Reduced renal function (AKI, CKD) decreases clearance, raising plasma levels. High ciprofloxacin + systemic exposure increases the risk of tendinopathy, QT prolongation, and CNS effects (seizure risk). Dose adjustment is required for eGFR <30.

A patient on tacrolimus (calcineurin inhibitor) starts clarithromycin for a respiratory infection. What is expected?

Answer: Tacrolimus levels rise dramatically — clarithromycin strongly inhibits CYP3A4 and P-glycoprotein, increasing tacrolimus absorption and reducing clearance

Tacrolimus has a narrow therapeutic index and is primarily metabolized by CYP3A4 and transported by P-glycoprotein. Clarithromycin (strong CYP3A4/P-gp inhibitor) can increase tacrolimus levels 5–10 fold, causing nephrotoxicity, neurotoxicity, and glucose intolerance. Urgent tacrolimus level monitoring and dose reduction are required.

Which medication causes a disulfiram-like reaction when taken with alcohol?

Answer: Metronidazole — inhibits aldehyde dehydrogenase, causing acetaldehyde accumulation

Metronidazole, like disulfiram, inhibits aldehyde dehydrogenase (ALDH). When alcohol is consumed, acetaldehyde accumulates causing flushing, nausea, vomiting, headache, and hypotension. Patients must be counseled to avoid all alcohol during metronidazole therapy and for 48 hours after the last dose.

A patient develops nephrotoxicity and ototoxicity while on tobramycin therapy. Which pharmacokinetic parameter most directly predicts these toxicities?

Answer: Elevated trough concentrations — reflect sustained high drug exposure that causes renal cortical and cochlear accumulation

Aminoglycoside nephrotoxicity and ototoxicity correlate with sustained drug exposure — specifically elevated trough concentrations (residual drug before next dose). Renal cortical accumulation occurs when trough levels remain high. This is why troughs are monitored and kept below 2 mg/L (gentamicin/tobramycin) in multiple-daily dosing.