Which blood pressure medications, such as Angiotensin-Converting Enzyme (ACE) inhibitors or Angiotensin II Receptor Blockers (ARBs), can cause hyperkalemia?

Blood Pressure Medications That Increase Potassium

Angiotensin-Converting Enzyme (ACE) inhibitors, Angiotensin II Receptor Blockers (ARBs), and Mineralocorticoid Receptor Antagonists (MRAs) are the primary blood pressure medications that can cause hyperkalemia by inhibiting the renin-angiotensin-aldosterone system. 1

Medications That Increase Potassium Levels

1. Renin-Angiotensin-Aldosterone System (RAAS) Inhibitors

• ACE Inhibitors

  • Examples: enalapril, lisinopril, captopril, ramipril, fosinopril, quinapril, perindopril, trandolapril 1
  • Mechanism: Block conversion of angiotensin I to angiotensin II, reducing aldosterone production and decreasing potassium excretion
  • Risk: Hyperkalemia occurs in approximately 6.4% of patients taking ACE inhibitors 1

• Angiotensin II Receptor Blockers (ARBs)

  • Examples: candesartan, losartan, valsartan 1
  • Mechanism: Block angiotensin II receptors, reducing aldosterone production
  • Risk: Similar hyperkalemia risk profile to ACE inhibitors 1

• Mineralocorticoid Receptor Antagonists (MRAs)

  • Examples: spironolactone, eplerenone 1
  • Mechanism: Directly block aldosterone receptors, preventing potassium excretion
  • Risk: Higher risk of hyperkalemia, especially when combined with other RAAS inhibitors 1

• Direct Renin Inhibitors

  • Example: aliskiren
  • Mechanism: Inhibit renin, reducing angiotensin II and aldosterone production
  • Risk: Can cause hyperkalemia, especially when combined with other RAAS inhibitors 2

2. Potassium-Sparing Diuretics

• Examples: amiloride, triamterene
• Mechanism: Block sodium channels in the distal tubule, reducing potassium secretion
• Risk: Can cause hyperkalemia, especially when combined with ACE inhibitors or ARBs 3

Risk Factors for Developing Hyperkalemia

1. Renal insufficiency (most important risk factor) 1
2. Diabetes mellitus 1
3. Advanced age 1
4. Heart failure 1
5. Combination therapy with multiple RAAS inhibitors 1
6. Concomitant use of NSAIDs 2
7. High potassium intake (supplements, salt substitutes) 1

Monitoring Recommendations

• Baseline assessment: Check serum potassium and renal function before starting therapy 1
• Follow-up monitoring: Check potassium and renal function within 1-2 weeks after:
  • Initiating therapy
  • Dose increases
  • Adding other medications that affect potassium 1
• Ongoing monitoring: At least yearly in stable patients 1

Clinical Implications and Management

Severity of Hyperkalemia

• Mild: 5.0-5.5 mmol/L
• Moderate: 5.5-6.0 mmol/L
• Severe: >6.0 mmol/L 4

Management Strategies

1. Medication adjustment:

   • Consider dose reduction rather than discontinuation of beneficial RAAS inhibitors 4
   • Avoid combination of ACE inhibitors with ARBs (increases hyperkalemia risk without additional benefit) 1
   • Avoid triple therapy with ACE inhibitor, ARB, and MRA 1

2. Preventive measures:

   • Limit dietary potassium intake (<40 mg/kg/day) 4
   • Avoid potassium supplements and potassium-containing salt substitutes 1
   • Consider adding a thiazide or loop diuretic to enhance potassium excretion 5

3. Patient education:

   • Inform about high-potassium foods to avoid 4
   • Advise on signs/symptoms of hyperkalemia to report

Special Considerations

• ACE inhibitors and thiazide diuretics: This combination may balance potassium effects, as ACE inhibitors tend to increase potassium while thiazides decrease it 3

• Dual RAAS blockade: The combination of ACE inhibitors and ARBs increases hyperkalemia risk to approximately 5% compared to ≤2% with monotherapy 6

• Heart failure patients: Despite increased hyperkalemia risk (5-10%), these patients often derive significant benefit from RAAS inhibitors 6

• Diabetes and CKD: These patients are at highest risk for hyperkalemia but may also receive the greatest benefit from RAAS inhibitors 1

Remember that while hyperkalemia is a concern with these medications, the absolute changes in serum potassium are generally small (approximately 0.1-0.3 mmol/L) and discontinuation rates due to hyperkalemia are relatively low (1-5%), even in high-risk patients 6.