Sulfamethoxazole-trimethoprim should be used with caution in older adults who are on ACE inhibitors, ARBs, or ARNIs and have decreased creatinine clearance because of risk of:

• A. Hyperkalemia
• B. Hyponatremia
• C. Hypokalemia
• D. Hypoglycemia.

Answer: (D)

The main idea is that this drug combination can cause hyperkalemia, especially in older adults with reduced kidney function. Trimethoprim in sulfamethoxazole-trimethoprim acts like a potassium-sparing agent by blocking the epithelial sodium channel in the distal nephron, which decreases potassium excretion. When someone is taking an ACE inhibitor, an ARB, or an ARNI, aldosterone levels drop, further reducing potassium excretion in the kidney. If creatinine clearance is diminished, the kidneys are less able to handle potassium, so the risk of dangerous high potassium (hyperkalemia) rises.

Hyponatremia and hypokalemia aren’t the primary concerns with this specific drug interaction, and hypoglycemia isn’t the key risk in this context. The combination’s standout danger in this setting is hyperkalemia, which can lead to serious cardiac effects if not monitored.