Q: 72-year-old male with a history of hypertension presented to the ER with dizziness. Patient found to have arrhythmias on tele-monitor. The lab showed hyperkalemia with 6.9 mEq/L. Wife reports starting on antibiotics for his chronic prostatitis about 2 weeks ago. Which drug interactions are suspected?
Answer: — Few common anti-hypertensives - and trimethoprim-sulfamethoxazole
Often ignored in the outpatient setting is the very low threshold of trimethoprim-sulfamethoxazole, popularly known as Bactrim, to cause hyperkalemia. Even without drug interaction, Trim-sulf can cause hyperkalemia, even in a conventional dose, though the risk is also dose-dependent. The trimethoprim component is responsible for hyperkalemia. Risk gets even higher if the patient is already on meds prone to cause hyperkalemia, like ACE inhibitors, ARBs, NSAIDs, beta-adrenergic blockers, or potassium-sparing diuretics. Also, obese people are at higher risk, as Trim-Sulf. is lipophilic. Plasma potassium concentration can change by a mean of 1.2 mEq/L within a week, even without any interaction or kidney impairment.
The mechanism of action is closure of the epithelial sodium channels in the collecting tubule. Also, note that ammonia production is inhibited in hyperkalemia, causing type 4 renal tubular acidosis (RTA).
Fortunately, all effects are reversible with discontinuation of the drug.
#pharmacology
References:
Velázquez H, Perazella MA, Wright FS, Ellison DH. Renal mechanism of trimethoprim-induced hyperkalemia. Ann Intern Med 1993; 119:296.
Perazella MA, Mahnensmith RL. Trimethoprim-sulfamethoxazole: hyperkalemia is an important complication regardless of dose. Clin Nephrol 1996; 46:187.
Weir MA, Juurlink DN, Gomes T, et al. Beta-blockers, trimethoprim-sulfamethoxazole, and the risk of hyperkalemia requiring hospitalization in the elderly: a nested case-control study. Clin J Am Soc Nephrol 2010; 5:1544.
Antoniou T, Gomes T, Juurlink DN, et al. Trimethoprim-sulfamethoxazole-induced hyperkalemia in patients receiving inhibitors of the renin-angiotensin system: a population-based study. Arch Intern Med 2010; 170:1045.

