From the Guidelines
Thiazide diuretics, such as chlorthalidone and hydrochlorothiazide, are the most likely antihypertensive medications to cause low sodium levels (hyponatremia) due to their mechanism of action and potential to interfere with the kidney's ability to dilute urine. These medications work by increasing sodium and water excretion through the kidneys, which helps lower blood pressure but can sometimes lead to excessive sodium loss 1. According to the 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults, thiazide or thiazide-type diuretics, including chlorthalidone, hydrochlorothiazide, indapamide, and metolazone, are associated with a risk of hyponatremia and hypokalemia 1.
The mechanism involves interference with the kidney's ability to dilute urine, leading to relatively more water retention compared to sodium. Patients taking these medications should be monitored for symptoms of hyponatremia such as confusion, headache, nausea, muscle cramps, and in severe cases, seizures or coma. Regular blood tests to check electrolyte levels are important, especially when starting therapy or adjusting dosages. Additionally, loop diuretics like furosemide and torsemide can also cause hyponatremia, as they inhibit reabsorption of sodium or chloride at the loop of Henle 1.
Key points to consider:
- Thiazide diuretics are particularly prone to causing hyponatremia, especially in elderly patients, those taking higher doses, or individuals with other risk factors like low body weight or concurrent use of other medications that affect sodium levels.
- Monitoring for symptoms of hyponatremia and regular blood tests to check electrolyte levels are crucial for patients taking these medications.
- The treatment goal is to eliminate clinical evidence of fluid retention, using the lowest dose possible to maintain euvolemia, and diuretics should not be used in isolation but always combined with other guideline-directed medical therapy (GDMT) for heart failure that reduces hospitalizations and prolongs survival 1.
From the Research
Anti-Hypertensive Medications that Cause Low Sodium
- Thiazide diuretics, such as hydrochlorothiazide and chlorthalidone, can cause low sodium levels (hyponatremia) as a side effect 2, 3, 4, 5, 6
- The mechanism of thiazide diuretics involves inhibiting the electroneutral Na(+)-Cl(-) cotransporter, which can lead to increased sodium excretion and potentially low sodium levels 4
- Chlorthalidone has been shown to be more effective than hydrochlorothiazide in reducing blood pressure, but may also be more likely to cause low sodium levels 3, 5, 6
- The risk of low sodium levels can be minimized by using low doses of thiazide diuretics and monitoring electrolyte levels regularly 2, 4, 5
Comparison of Thiazide Diuretics
- Hydrochlorothiazide and chlorthalidone are two commonly used thiazide diuretics, with chlorthalidone being more potent and longer-acting 3, 5, 6
- Indapamide is another thiazide-like diuretic that has been shown to be effective in reducing blood pressure, but may have a different side effect profile compared to hydrochlorothiazide and chlorthalidone 3, 5
- The choice of thiazide diuretic should be based on individual patient characteristics and medical history, as well as the potential risks and benefits of each medication 2, 3, 4, 5, 6