Lisinopril Does Not Cause Hypokalemia but May Cause Hyponatremia
Lisinopril does not cause hypokalemia but rather tends to cause hyperkalemia, and it has been associated with hyponatremia in some case reports.
Effects on Potassium Levels
ACE inhibitors like lisinopril are associated with an increased risk of hyperkalemia (elevated potassium), not hypokalemia, especially in patients with chronic kidney disease or those taking potassium supplements or potassium-sparing drugs 1.
The FDA drug label for lisinopril specifically notes that hyperkalemia (serum potassium greater than 5.7 mEq/L) occurred in 2.2% of lisinopril-treated hypertensive patients and 4.8% of heart failure patients 2.
Unlike thiazide diuretics, which are commonly monitored for hypokalemia, ACE inhibitors like lisinopril work through inhibition of the renin-angiotensin-aldosterone system, which typically leads to potassium retention rather than depletion 1.
Clinical trials of lisinopril have demonstrated that it does not produce hypokalemia, which is actually considered a beneficial aspect of its safety profile compared to some other antihypertensive medications 3.
Effects on Sodium Levels
The FDA drug label for lisinopril lists hyponatremia as a potential post-marketing adverse reaction under "Metabolism and nutrition disorders" 2.
There are several case reports documenting severe hyponatremia associated with lisinopril therapy, including cases where sodium levels dropped to dangerous levels (as low as 101-109 mmol/L) 4, 5, 6.
In one documented case, a patient's serum sodium dropped from 134 to 126 mmol/L after restarting lisinopril, and maintained normal levels after the medication was discontinued 5.
The mechanism may involve inappropriate antidiuresis secondary to ACE inhibitor therapy, potentially combined with polydipsia in some patients 6.
Clinical Implications and Monitoring
When prescribing lisinopril, clinicians should:
- Monitor serum potassium levels regularly, especially in patients with risk factors for hyperkalemia (kidney disease, concurrent use of potassium-sparing medications) 1, 7
- Be aware of the potential for hyponatremia, particularly in elderly patients or those with other risk factors for electrolyte disturbances 2, 4
- Consider checking sodium levels if patients on lisinopril develop symptoms such as confusion, seizures, or altered mental status 5, 6
Risk factors that increase the likelihood of hyperkalemia with lisinopril include: advanced age, reduced eGFR, diabetes, heart failure, use of potassium supplements, and concurrent use of potassium-sparing diuretics 7.
Comparison with Other Antihypertensives
Unlike thiazide diuretics (such as chlorthalidone and hydrochlorothiazide) which are known to cause hypokalemia and hyponatremia, ACE inhibitors like lisinopril have opposite effects on potassium balance 1.
When choosing between antihypertensive medications, the American College of Cardiology/American Heart Association guidelines recommend considering the different electrolyte effects of various drug classes 1.