What anti-hypertensive medications can cause hyponatremia?

Antihypertensive Medications That Can Cause Hyponatremia

Thiazide and thiazide-like diuretics are the antihypertensive medications most strongly associated with hyponatremia, and should be used with caution in high-risk patients, particularly elderly women. 1

Specific Antihypertensive Medications Associated with Hyponatremia

Primary Culprits:

1. Thiazide and Thiazide-like Diuretics
   • Chlorthalidone (12.5-25 mg daily) 1
   • Hydrochlorothiazide (25-50 mg daily) 1
   • Indapamide (1.25-2.5 mg daily) 1
   • Metolazone (2.5-5 mg daily) 1

Secondary Culprits:

1. Loop Diuretics - Less commonly cause hyponatremia than thiazides 1

   • Furosemide
   • Bumetanide
   • Torsemide

2. Potassium-Sparing Diuretics - When used in combination with other diuretics 1

   • Spironolactone
   • Eplerenone
   • Amiloride

Mechanism of Diuretic-Induced Hyponatremia

Thiazide diuretics cause hyponatremia through multiple mechanisms:

• Impairment of urinary dilution capacity 2, 3
• Renal loss of sodium and potassium 2
• Stimulation of antidiuretic hormone (ADH) release 2, 3
• Reduction in glomerular filtration rate 2
• Enhanced proximal water reabsorption 2
• Possible dipsogenic effect (increased thirst) 2

High-Risk Populations

Patients at highest risk for developing thiazide-induced hyponatremia include:

• Elderly patients, particularly women 1, 3
• Patients with low body mass 3
• Patients with chronic high water intake 2
• Patients taking other medications that impair water excretion, such as selective serotonin reuptake inhibitors (SSRIs) 4
• Patients with psychogenic polydipsia 2

Clinical Presentation and Timing

• Hyponatremia typically develops within the first 2 weeks of starting thiazide therapy but can occur at any time during treatment 5, 3
• Symptoms range from mild (weakness, nausea) to severe (seizures, coma) 6
• Even mild chronic hyponatremia is associated with cognitive impairment, gait disturbances, and increased rates of falls and fractures 6

Monitoring and Prevention

1. Before initiating thiazide diuretics:

   • Assess baseline serum sodium levels
   • Evaluate risk factors for hyponatremia

2. After initiating thiazide diuretics:

   • Check electrolytes within 1-2 weeks of starting therapy 7
   • Monitor more frequently in high-risk patients
   • Consider lower starting doses in elderly patients

3. Ongoing monitoring:

   • Regular electrolyte checks, particularly after dose increases
   • Educate patients about symptoms of hyponatremia

Management of Diuretic-Induced Hyponatremia

1. Mild to moderate hyponatremia:

   • Discontinue the thiazide diuretic 5
   • Implement fluid restriction 5
   • Consider switching to a different class of antihypertensive medication

2. Severe symptomatic hyponatremia:

   • Treat as a medical emergency
   • Consider hypertonic saline for severely symptomatic patients 6
   • Monitor for overly rapid correction, which can lead to osmotic demyelination 6, 2

Alternative Antihypertensive Options for Patients with History of Hyponatremia

For patients with a history of diuretic-induced hyponatremia, consider:

• ACE inhibitors (e.g., lisinopril, enalapril) 1
• Angiotensin receptor blockers (e.g., losartan, valsartan) 1
• Calcium channel blockers (e.g., amlodipine, diltiazem) 1
• Beta-blockers (e.g., metoprolol, bisoprolol) 1

Important Clinical Pitfalls to Avoid

• Don't assume hyponatremia is always due to volume depletion; many patients with thiazide-induced hyponatremia appear euvolemic 3
• Be cautious with concurrent use of thiazides and SSRIs, as this combination may have synergistic effects on hyponatremia 4
• Avoid thiazides in patients with chronically high water intake or those who depend on maximally dilute urine to maintain fluid balance 2
• Be aware that inadvertent rapid correction of hyponatremia is common in thiazide-induced hyponatremia when the diuretic is discontinued 2