Drug-Induced Hyperkalemia

Abstract

Hyperkalemia is a common clinical condition that can be defined as a serum potassium concentration exceeding 5.0 mmol/L. Drug-induced hyperkalemia is the most important cause of increased potassium levels in everyday clinical practice. Drug-induced hyperkalemia may be asymptomatic. However, it may be dramatic and life threatening, posing diagnostic and management problems. A wide range of drugs can cause hyperkalemia by a variety of mechanisms. Drugs can interfere with potassium homoeostasis either by promoting transcellular potassium shift or by impairing renal potassium excretion. Drugs may also increase potassium supply. The reduction in renal potassium excretion due to inhibition of the renin-angiotensin-aldosterone system represents the most important mechanism by which drugs are known to cause hyperkalemia. Medications that alter transmembrane potassium movement include amino acids, beta-blockers, calcium channel blockers, suxamethonium, and mannitol. Drugs that impair renal potassium excretion are mainly represented by angiotensin-converting enzyme inhibitors, angiotensin-II receptor blockers, direct renin inhibitors, nonsteroidal anti-inflammatory drugs, calcineurin inhibitors, heparin and derivatives, aldosterone antagonists, potassium-sparing diuretics, trimethoprim, and pentamidine. Potassium-containing agents represent another group of medications causing hyperkalemia. Increased awareness of drugs that can induce hyperkalemia, and monitoring and prevention are key elements for reducing the number of hospital admissions, morbidity, and mortality related to drug-induced hyperkalemia.

Pharmacology of Heparin and Related Drugs

“…The effect appears to be independent of anticoagulant activity, occurs at relatively low doses and is specific to aldosterone, mediated at least in part by reduced angiotensin II receptor expression in the zona glomerulosa (Oster et al, 1995). In the majority of patients receiving heparin, physiologic compensation prevents hyperkalemia from occurring; however, monitoring of serum potassium levels is prudent in individuals with impaired renal function or diabetes or in the presence of additional medications that promote potassium retention (e.g., aldosterone receptor antagonists, angiotensinconverting enzyme inhibitors) (Preston et al, 1998;Ben Salem et al, 2014).…”

Tolerability of Antihypertensive Medications in Older Adults

“…Major drugs include ACEIs, ARBs, direct renin inhibitors (DRIs), aldosterone antagonists, and potassiumsparing diuretics [35][36][37]. The combination of ACEIs or ARBs with aldosterone antagonists is particularly noteworthy and calls for monitoring of potassium levels, particularly in older adults and in the presence of CKD [36].…”

Focus on Hyperkalemia Management: Expert Consensus and Economic Impacts

“…With regard to the identification of any underlying causes, the drugs listed in Table 5 have been known to cause hyperkalemia. 20 The panel commented that current options to manage hyperkalemia on a chronic basis are limited, and robust evidence supporting their efficacy and safety in the outpatient setting is lacking. The panel recommended that more clinical trials be conducted.…”