title: Hyperkalemia and trimethoprim-sulfamethoxazole: a new problem emerges 25 years later.
abstract: Trimethoprim-sulfamethoxazole is a frequently prescribed antibiotic with a wide spectrum of antimicrobial activity. A previously unreported and potentially lethal adverse reaction associated with "high dose" trimethoprim-sulfamethoxazole therapy, hyperkalemia, was described. Subsequent to the descriptions of hyperkalemia with "high dose" trimethoprim-sulfamethoxazole, a handful of cases noted the development of hyperkalemia with "standard dose" trimethoprim-sulfamethoxazole in elderly patients without evidence of an obvious defect in potassium homeostasis. A surveillance study of patients treated with "standard dose" trimethoprim-sulfamethoxazole as compared to similar controls treated with other antibiotics confirmed the rise in potassium associated with trimethoprim-sulfamethoxazole therapy. Recognition of this potassium disorder led to investigation and description of the mechanism by which trimethoprim-sulfamethoxazole-induced hyperkalemia. Trimethoprim was found to act like the potassium-sparing diuretic amiloride and reduce renal potassium excretion. Hence, trimethoprim-sulfamethoxazole therapy was found to be associated with a new adverse reaction, hyperkalemia, nearly 25 years after its introduction into clinical practice as an antimicrobial agent.
authors.affiliation: Department of Medicine, Yale University School of Medicine, New Haven, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Perazella
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006947:Hyperkalemia / Q000139:chemically induced*; D007668:Kidney / Q000187:drug effects; D011188:Potassium / Q000378:metabolism; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology
chemical_list: D000890:Anti-Infective Agents; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D011188:Potassium