Deskripsi
Trimethoprim blocks renal tubular secretion of potassium, acting like a potassium-sparing diuretic; combined with losartan's reduction of aldosterone-mediated potassium excretion, the risk of hyperkalaemia is substantially increased.
Mekanisme
Trimethoprim inhibits the epithelial sodium channel (ENaC) in the distal nephron, reducing potassium secretion; losartan blocks angiotensin II AT1 receptors, lowering aldosterone-driven potassium excretion; additive potassium retention is the result.
Signifikansi Klinis
Population-based studies associate trimethoprim use with elevated sudden death risk in patients on renin-angiotensin-aldosterone inhibitors, attributed to hyperkalaemia-induced arrhythmia.
Penatalaksanaan
Monitor serum potassium within 1 week of starting trimethoprim in patients on ARBs; reduce potassium supplementation; use an alternative antibiotic in high-risk patients.