What are the mechanisms by which commonly used medications cause hyperkalemia?
Mechanisms by Which Commonly Used Medications Cause Hyperkalemia
| CLASS | MECHANISM |
|---|---|
| Potassium containing drugs like KCl, penicillin G, potassium citrate | Increased intake of potassium usually in the setting of decreased GFR |
| β-blockers | Inhibit renin release and cellular uptake of potassium |
| ACE inhibitors like lisinopril, captopril, enalapril, ramipril | Inhibit conversion of angiotensin I to angiotensin II, leading to ↓ aldosterone effect |
| Angiotensin receptor blockers like losartan, valsartan | Inhibit activation of angiotensin II receptors by angiotensin II and thus ↓ aldosterone synthesis and secretion |
| Direct renin inhibitors | renin activity leading to ↓ angiotensin II production |
| Heparin | Inhibits enzyme aldosterone synthase in adrenals |
| Mineralocorticoid receptor antagonists like spironolactone | Block aldosterone receptor activation |
| Potassium-sparing diuretics like amiloride, triamterene (trimethoprim and pentamidine have similar structure) | Block apical ENaC in collecting duct, thus ↓ the electrical gradient needed for potassium secretion |
| NSAIDs and COX-2 inhibitors | Inhibit prostaglandin stimulation of collecting duct secretion; inhibit renin release |
| Digoxin | Inhibit Na + -K + -ATPase pump on collecting duct necessary for providing potassium for secretion |
| Calcineurin inhibitors (tacrolimus, cyclosporine) | Activates WNK3 and WNK4 which upregulate sodium chloride cotransporter (thiazide sensitive transporter). This decreases sodium delivery to the ENaC needed for potassium secretion |
ACE , Angiotensin converting enzyme; COX-2 , cyclooxygenase-2; ENaC , epithelial sodium channel; GFR , glomerular filtration rate; NSAIDs , nonsteroidal anti-inflammatory drugs.Modified from Weiner, D. I., Linas, S. L., & Wingo C. S. (2015). Disorders of potassium metabolism. In Comprehensive clinical nephrology . Philadelphia: Elsevier Saunders.
