Trimethoprim

Key points

• Trimethoprim is an antibiotic, mainly used in the management of urinary tract infections. Mechanism of action
• interferes with DNA synthesis by inhibiting dihydrofolate reductase Adverse effects
• myelosuppression
• HYPERKALAEMIA: trimethoprim blocks the epithelial sodium channel in the distal tubule (an amiloride-like effect), reducing potassium excretion · risk is greatest in the elderly, in renal impairment, and with ACE INHIBITORS, ANGIOTENSIN-RECEPTOR BLOCKERS, spironolactone or potassium supplements — a frequently examined and clinically dangerous combination.
• PREGNANCY: trimethoprim is a FOLATE ANTAGONIST and is avoided in the FIRST TRIMESTER because of neural tube defect risk · nitrofurantoin is generally preferred earlier in pregnancy, but is itself avoided at TERM because of neonatal haemolysis — the two drugs are avoided at opposite ends of pregnancy, which is the classic trap.
• transient rise in creatinine: trimethoprim competitively inhibits the tubular secretion of creatinine resulting in a temporary increase which reverses upon stopping the drug