Drug Interactions and Adverse Effects Flashcards

A patient on amlodipine for hypertension develops peripheral edema. What is the mechanism of this adverse effect?

Answer: Dihydropyridine CCBs dilate arterioles more than venules, causing increased hydrostatic pressure in capillary beds and fluid extravasation

Dihydropyridine calcium channel blockers (amlodipine, nifedipine) selectively dilate arterioles. The resulting arteriolar dilation without proportional venodilation increases capillary hydrostatic pressure, causing fluid to move into interstitial spaces — dependent edema in the ankles/legs. This is pharmacological, not cardiogenic.

A patient on azathioprine develops pancytopenia. Thiopurine methyltransferase (TPMT) genotyping reveals poor metabolizer status. What does this mean?

Answer: TPMT deficiency leads to accumulation of active 6-thioguanine nucleotides, causing severe myelosuppression

TPMT methylates azathioprine to inactive 6-MMP. Poor metabolizers (TPMT-deficient) channel more azathioprine into 6-thioguanine nucleotides (active but myelotoxic metabolites), causing severe bone marrow suppression at standard doses. TPMT genotyping or phenotyping before starting azathioprine identifies at-risk patients.

A patient on carbamazepine develops hyponatremia. What is the mechanism?

Answer: Carbamazepine enhances ADH effect on renal tubules, causing SIADH (syndrome of inappropriate antidiuretic hormone secretion)

Carbamazepine causes SIADH by potentiating the effect of ADH (vasopressin) on renal collecting ducts, increasing water reabsorption and diluting serum sodium. SIADH causes hyponatremia, which can manifest as confusion, seizures, or coma. It is more common in elderly patients and those on high doses.

A pharmacist is reviewing a patient on digoxin who has developed hypercalcemia. What is the concern?

Answer: Hypercalcemia potentiates digoxin toxicity — calcium and digoxin have synergistic effects on cardiac automaticity

Calcium and digoxin have synergistic effects on cardiac myocyte contractility and automaticity. Hypercalcemia potentiates digoxin toxicity even at therapeutic digoxin levels, increasing the risk of arrhythmias. The mnemonic: 'digoxin and calcium are toxic twins — when calcium goes up, digoxin toxicity risk goes up.'

A patient develops severe hypertension and cardiac arrhythmias after being given cocaine during a cardiac procedure. What pharmacological treatment should be avoided?

Answer: Non-selective beta-blockers (e.g., propranolol) — cause unopposed alpha-1 stimulation worsening hypertension

Cocaine causes sympathomimetic toxicity by blocking norepinephrine/dopamine reuptake. In cocaine-associated chest pain/hypertension, non-selective beta-blockers are contraindicated because blocking beta-2 (vasodilation) while leaving alpha-1 (vasoconstriction) unopposed worsens hypertension and coronary vasospasm. Benzodiazepines are first-line.

A patient on levodopa/carbidopa develops sudden involuntary writhing movements ('dyskinesias'). What is the pharmacological explanation?

Answer: Levodopa-induced dyskinesias result from dopaminergic receptor sensitization and pulsatile stimulation after years of therapy

Long-term levodopa therapy causes pulsatile (non-physiological) dopamine receptor stimulation due to short half-life of levodopa. This leads to receptor sensitization and ultimately to dyskinesias (peak-dose) and wearing-off phenomenon. Management: extended-release formulations, dose reduction, adding MAO-B inhibitor, or using apomorphine pump.