Sulfonamides

Bacteria must make their own folate (folic acid) to build DNA — they can’t absorb it from the environment the way human cells do. Sulfonamides exploit this: sulfamethoxazole blocks an early enzyme (dihydropteroate synthase) in the bacterial folate pathway, and its partner trimethoprim blocks a later one (dihydrofolate reductase). Hitting two sequential steps produces a powerful synergistic, often bactericidal effect — which is why the two are combined as TMP-SMX (Bactrim).

Because human cells get folate from the diet and don’t use these enzymes the same way, the drug is relatively selective for bacteria. TMP-SMX is a workhorse for UTIs, MRSA skin infections, and Pneumocystis (PCP) prophylaxis/treatment.

Four safety themes define sulfonamides. (1) Sulfa allergy: they are the classic "sulfa" drugs and can cause severe skin reactions — from rash to Stevens-Johnson syndrome / toxic epidermal necrolysis (SJS/TEN). (2) Crystalluria: the drug can precipitate in the urine and injure the kidney — so patients must push fluids. (3) Hyperkalemia: trimethoprim blocks a sodium channel in the kidney (amiloride-like), raising potassium — important with ACE-I/ARBs, potassium-sparing diuretics, or renal disease.

(4) The folate connection reaches human cells too at the margins: it can cause blood dyscrasias (megaloblastic anemia, leukopenia), and in a newborn the sulfa displaces bilirubin from albumin, causing kernicterus — which is why it’s avoided in late pregnancy and infants under 2 months. It also potentiates warfarin and methotrexate.