Drug-Induced Peripheral (Leg) Edema

Peripheral edema — swelling of the legs and ankles due to fluid accumulation in the interstitial tissue — is a well-recognised adverse effect of several commonly used drug classes. All four classes listed in this question are known causes, making "1, 2, 3 and 4" the correct answer.

Analysis of Each Drug Class

• 1. Calcium channel blockers (CCBs): Dihydropyridine CCBs (e.g., amlodipine, nifedipine) cause dose-dependent peripheral edema due to selective precapillary arteriolar vasodilatation. This increases hydrostatic pressure in the capillary bed without a compensatory dilation of the postcapillary venules, causing fluid to leak into the interstitium — a mechanism unrelated to sodium/water retention or heart failure. This is one of the most common reasons CCBs are discontinued.
• 2. NSAIDs: Non-steroidal anti-inflammatory drugs inhibit cyclooxygenase (COX), reducing renal prostaglandin synthesis. Since renal prostaglandins normally maintain glomerular perfusion and oppose sodium reabsorption, their inhibition leads to sodium and water retention, causing edema, and can also precipitate or worsen hypertension and heart failure.
• 3. Glucocorticoids: Corticosteroids (e.g., prednisolone) possess intrinsic mineralocorticoid activity, which promotes renal sodium and water reabsorption at the distal tubule, expanding extracellular fluid volume and producing dependent edema, especially with high doses or prolonged use.
• 4. Mineralocorticoids: Agents like fludrocortisone directly act on mineralocorticoid receptors in the renal collecting duct, markedly increasing sodium (and consequently water) reabsorption in exchange for potassium. This is the most direct and potent mechanism of fluid retention among the options, producing significant edema.

Conclusion

Each of the four drug classes — calcium channel blockers, NSAIDs, glucocorticoids, and mineralocorticoids — produces leg swelling, albeit through distinct mechanisms (altered capillary hemodynamics for CCBs versus renal sodium/water retention for the other three). Therefore, the correct combination is 1, 2, 3 and 4.