Drugs Associated with Hyperkalemia

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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.


  1. clin pharmacist here, i spoke to nephrologist about K being 7 in a esrd hd pt and she that told me ace-i in esrd pt with hd should not usually cause hyperkalemia? she said it due to mechanism, which to my knowledge is 2/2 to aldosterone, so i'm unsure how this is related to the hd patients and to my surprise there are some limited published studies that does provide support for this, can one of you clarify this?

  2. I would add eplerenone and also Beta antagonists (high dose) to the list as well

  3. A previous nephrologist prescribed Fludrocort. Supposedly it lowered K but probably increased my BP. Any comments on this approach?

  4. f/u…that would be tekturna and now valturna (sp?)

  5. minor point…don't forget the renin inhibitors. They are being pushed hard to the primary care docs by Novartis

  6. I believe that I read in a NEJM article that calcineurin inhibitors also inhibit COX-2 in similar fashion to NSAIDs. Another mechanism that CNIs may lead to hyperkalemia.

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