Hyperkalemia Side Effect

Potassium is an essential mineral micronutrient and an important electrolyte required for physiological functioning. Hyperkalemia is a medical condition in which a serum potassium concentration is greater than 5.0 mmol/L.

Abnormally high potassium levels can cause severe cardiac electrophysiology alterations, such as cardiac arrhythmias. Severe hyperkalemia (potassium >6.5 mmol/L) is potentially life-threatening condition.

Generally, hyperkalemia may be caused by the following mechanisms17:

  • excessive potassium intake
  • disturbed cellular uptake of potassium
  • impaired renal excretion of potassium

The impairment of renal potassium excretion due to inhibition of the renin-angiotensin-aldosterone system is the most common mechanism by which medications cause hyperkalemia. Certain medications may also increase potassium supply. Drug-drug interactions that result in increased potassium levels are also common.

Medicines affecting the renin-angiotensin system are the most common cause of hyperkalaemia. List of drugs that may cause Hyperkalemia as a side effect:

Drug Incidence
Amiloride (Midamor)6
Triamterene (Dyrenium)5
Diminishes potassium secretion by reducing the electrical gradient between the intracellular space and the renal tubule
Epsilon-aminocaproic acid (Amicar)
Cationic amino acids enter cells in exchange for potassium, causing hyperkalemia1
Angiotensin Receptor Blockers (ARB)2 10-30%, ARBs reduce renal potassium excretion via decreased aldosterone synthesis. ARBs may be more likely to cause hyperkalemia than ACE inhibitors3
Angiotensin-Converting Enzyme Inhibitors (ACEi)2, 3 up to 20.4%
Beta blockers7 1-5%
Decrease sodium-potassium adenosine triphosphatase activity
Cyclosporine (Sandimmune)4 Suppresses renin release, leading to decreased aldosterone synthesis
Digoxin at toxic levels8 Extremely high serum concentrations of digixin produce hyperkalemia
Fluoride toxicity9 Most common in patients on dialysis who drink water with high fluoride levels
Glucose infusions Hypertonicity caused by hyperglycemia from glucose infusions can drive potassium out of the intracellular space.leading to hyperkalemia. Hyperkalemia may occur with continuous infusions or with boluses of hypertonic glucose. May be present with hypertonicity caused by other agents such as mannitol Osmitrol
Heparins10 Inhibit adrenal aldosterone production+Can cause hyperkalemia in patients with decreased renal function
NSAIDs11 Decreased renal prostaglandin synthesis leads to decreased afferent arteriolar flow, suppressing renin and aldosterone secretion. The strongest risk factors for NSAID-induced hyperkalemia include prior episode of hyperkalemia, Chronic kidney disease, diabetes, and use of potassium-sparing diuretics 12
Penicillin G potassium13 Can cause hyperkalemia in patients with impaired renal function caused by increased potassium load
Potassium-sparing diuretics Blockade of luminal sodium channels. Hyperkalemia is a main complication of the potassium-sparing diuretics
Potassium supplements
Salt substitutes
Consumption of potassium can lead to hyperkalemia, particularly if renal function is impaired
Spironolactone (Aldactone) The risk is higher when spironolactone is used concomitantly with ACE inhibitors14
Succinylcholine (Anectine)15 Increases nicotinic acetylcholine receptors in damaged skeletal muscles e.g. thermal trauma
Tacrolimus (Prograf) Causes hyperkalemia by various mechanisms affecting potassium in the distal tubule16
Trimethoprim (Proloprim)18
Pentamidine (Pentam 300)19
Decreases renal potassium excretion through the competitive inhibition of epithelial sodium channels in the distal nephron


Risk factors for drug-induced hyperkalemia:

  • chronic renal insufficiency
  • renal disease
  • increasing age
  • dehydration
  • hypoaldosteronism
  • metabolic acidosis
  • diabetes mellitus, insulin deficiency
  • increased potassium intake
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  • 2. Raebel MA. Hyperkalemia associated with use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. Cardiovasc Ther. 2012 Jun;30(3):e156-66. PubMed
  • 3. Sadjadi SA, McMillan JI, Jaipaul N, Blakely P, Hline SS. A comparative study of the prevalence of hyperkalemia with the use of angiotensin-converting enzyme inhibitors versus angiotensin receptor blockers. Ther Clin Risk Manag. 2009 Jun;5(3):547-52. PubMed
  • 4. Caliskan Y, Kalayoglu-Besisik S, Sargin D, Ecder T. Cyclosporine-associated hyperkalemia: report of four allogeneic blood stem-cell transplant cases. Transplantation. 2003 Apr 15;75(7):1069-72. PubMed
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  • 7. Mandić D, Nezić L, Skrbić R. Severe hyperkalemia induced by propranolol. Med Pregl. 2014 May-Jun;67(5-6):181-4. PubMed
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  • 10. Oster JR, Singer I, Fishman LM. Heparin-induced aldosterone suppression and hyperkalemia. Am J Med. 1995 Jun;98(6):575-86. PubMed
  • 11. Kim S, Joo KW. Electrolyte and Acid-Base Disturbances Associated with Nonsteroidal Anti-Inflammatory Drugs. Electrolyte and Acid-base disturbances associated with non-steroidal anti-inflammatory drugs. Electrolyte Blood Press. 2007 Dec;5(2):116-25. PubMed
  • 12. Lafrance JP, Miller DR. Dispensed selective and nonselective nonsteroidal anti-inflammatory drugs and the risk of moderate to severe hyperkalemia: a nested case-control study. Am J Kidney Dis. 2012;60:82-89.
  • 13. Thiele A, Rehman HU. Hyperkalemia caused by penicillin. Am J Med. 2008 Aug;121(8):e1-2.
  • 14. Juurlink DN, Mamdani MM, Lee DS, Kopp A, Austin PC, Laupacis A, Redelmeier DA. Rates of hyperkalemia after publication of the Randomized Aldactone Evaluation Study. N Engl J Med. 2004 Aug 5;351(6):543-51. PubMed
  • 15. Gronert GA, Theye RA Pathophysiology of hyperkalemia induced by succinylcholine. Anesthesiology. 1975 Jul;43(1):89-99. PubMed
  • 16. Dick TB, Raines AA, Stinson JB, Collingridge DS, Harmston GE. Fludrocortisone is effective in the management of tacrolimus-induced hyperkalemia in liver transplant recipients. Transplant Proc. 2011 Sep;43(7):2664-8. PubMed
  • 17. Perazella MA. Drug-induced hyperkalemia: old culprits and new offenders. Am J Med. 2000 Sep;109(4):307-14.
  • 18. Velázquez H, Perazella MA, Wright FS, Ellison DH. Renal mechanism of trimethoprim-induced hyperkalemia. Ann Intern Med. 1993 Aug 15;119(4):296-301. PubMed
  • 19. Kleyman TR, Roberts C, Ling BN. A mechanism for pentamidine-induced hyperkalemia: inhibition of distal nephron sodium transport. Ann Intern Med. 1995 Jan 15;122(2):103-6. PubMed

Published: January 17, 2017
Last updated: February 10, 2017


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