Drugs Associated with Hyperkalemia

There are a variety of drugs which can result in hyperkalemia, via a variety of mechanisms. Here are a list of some of the common offenders, categorized loosely based on mechanism, though admittedly there is some overlap between categories:

1. Drugs which cause translocation of K from the intracellular to the extracellular fluid: these include succinylcholine, isoflurane, minoxidil, and beta-blockers.

2. Potassium-Sparing Diuretics: drugs such as spironolactone (mineralocorticoid receptor antagonists) and amiloridine/triamterene (blockers of the ENaC) are common causers of hyperkalemia.

3. Inhibitors of renin-angiotensin-aldosterone axis: ACE-inhibitors, angiotensin receptor blockers.

4. Hyperosmolarity: hyperosmolarity induces water efflux out of cells, and by solvent drag increases intravascular potassium concentrations. Drugs such as mannitol can therefore cause translocational hyperkalemia.

5. NSAIDs: NSAIDs can lower renin secretion, which is normally mediated in part by locally-produced prostaglandins.

6. Bactrim: the hyperkalemia induced by Bactrim is via an ENaC inhibitory effect exerted by the trimethoprim moiety. Pentamidine induced hyperkalemia via a similar mechanism.

7. calcineurin inhibitors (e.g., cyclosporine, tacrolimus): it is postulated that these medications inhibit renal tubular responsiveness to aldosterone.

8. heparin & ketoconazole: these drugs may be associated by hyperkalemia by inhibiting aldosterone synthesis.

9. digitalis: digitalis inhibits the Na-K ATPase (which pumps 3 Na out of the cell and 2 K in); as such, it can result in hyperkalemia and a variety of cardiac arrhythmias.