sulfamethoxazole
Summary
Sulfamethoxazole is a sulfonamide antibiotic that inhibits bacterial folate synthesis by blocking dihydropteroate synthase, preventing conversion of PABA to dihydrofolate. It is almost always combined with trimethoprim (TMP-SMX/co-trimoxazole) for synergistic antibacterial effect. It is used for UTIs, PCP prophylaxis/treatment, and other infections.
Detail
Mechanism: Sulfamethoxazole is a structural analog of PABA that competitively inhibits dihydropteroate synthase, blocking folate synthesis in bacteria. Trimethoprim inhibits dihydrofolate reductase downstream, so the combination produces sequential blockade of the folate pathway, yielding bactericidal synergy despite each drug being bacteriostatic alone. Humans are spared significant toxicity because we obtain folate from diet and lack the PABA-dependent synthesis pathway, though TMP has some effect on mammalian DHFR at high doses (mitigated by folinic acid/leucovorin rescue when needed).
Spectrum/Uses: TMP-SMX covers many Gram-positive and Gram-negative organisms including E. coli, Klebsiella, Proteus, Salmonella, Shigella, Stenotrophomonas maltophilia, and importantly Pneumocystis jirovecii (treatment and prophylaxis in HIV/immunocompromised patients with CD4 <200), Toxoplasma gondii prophylaxis, Nocardia, and community-acquired MRSA skin infections. Also used for UTIs, otitis media, traveler's diarrhea, and as prophylaxis in transplant/immunocompromised patients.
Adverse effects: Hypersensitivity reactions (rash, Stevens-Johnson syndrome/TEN especially in HIV patients), hemolytic anemia in G6PD deficiency, hyperkalemia (TMP acts like amiloride on renal tubules), megaloblastic anemia/leukopenia/thrombocytopenia from folate antagonism, kernicterus in newborns (displaces bilirubin from albumin) - contraindicated in pregnancy near term and in infants <2 months, nephrotoxicity via crystalluria (ensure hydration), and photosensitivity.
Drug interactions: Potentiates warfarin (displaces from albumin, inhibits CYP2C9), can cause hypoglycemia with sulfonylureas, increases methotrexate toxicity (both are folate antagonists), risk of hyperkalemia with ACE inhibitors/ARBs/potassium-sparing diuretics.
Boards pearls: Classic cause of drug-induced Stevens-Johnson syndrome/TEN and drug-induced hyperkalemia. Remember G6PD deficiency as contraindication. High-yield for questions on PCP prophylaxis dosing and folate pathway pharmacology diagrams (PABA → dihydrofolate → tetrahydrofolate, showing sulfonamide vs. trimethoprim vs. methotrexate sites of action).
Sources
- First Aid for the USMLE Step 1
- Katzung's Basic and Clinical Pharmacology
- Sanford Guide to Antimicrobial Therapy
- Goodman & Gilman's The Pharmacological Basis of Therapeutics
Reviewed by AnkiBoss editorial — medical student review. Information here is for study reference only and is not medical advice. Spotted an error? Let us know.