What medications can cause hyponatremia?

Medications That Can Cause Hyponatremia

Numerous medications can cause hyponatremia, with the most common culprits being thiazide diuretics, selective serotonin reuptake inhibitors (SSRIs), and antiepileptic drugs such as carbamazepine. These medications can significantly impact morbidity and mortality through their effects on serum sodium levels.

Major Drug Classes Associated with Hyponatremia

1. Diuretics

• Thiazide diuretics: Most commonly implicated in drug-induced hyponatremia 1
  • Mechanism: Impair urinary dilution, cause renal sodium loss, stimulate antidiuretic hormone (ADH), and may have dipsogenic effects 2
  • Risk is particularly high in elderly patients and those with pre-existing low-normal sodium levels

2. Psychiatric Medications

• Selective Serotonin Reuptake Inhibitors (SSRIs):

  • All SSRIs can cause hyponatremia through syndrome of inappropriate antidiuretic hormone secretion (SIADH) 3, 4
  • Examples include:
    • Fluoxetine (Prozac) 3
    • Sertraline (Zoloft) 4
    • Citalopram, Escitalopram 5
    • Paroxetine, Fluvoxamine 6
  • Highest risk during first few weeks of treatment 7
  • Frequency estimated at up to 8 per 1,000 in elderly female patients 7

• Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs):

  • Venlafaxine 5

• Antiepileptic Medications:

  • Carbamazepine: Causes SIADH, especially at higher doses 8
  • Risk appears to be dose-related 8

3. Cardiovascular Medications

• Beta-blockers: Can potentially cause hyponatremia by affecting the aldosterone-to-renin ratio 9
• ACE inhibitors: May contribute to hyponatremia, particularly when combined with other at-risk medications 5

Risk Factors for Drug-Induced Hyponatremia

1. Age: Elderly patients are at significantly higher risk 4, 7, 6
2. Gender: Women are more susceptible than men 7, 5
3. Low body weight 5
4. Baseline sodium at lower end of normal range 5
5. Concomitant use of multiple at-risk medications 2
   • Particularly dangerous combinations:
     • Thiazide diuretics + SSRIs (synergistic effect) 2
6. Underlying conditions:
   • Heart failure 1, 9
   • Cirrhosis 1
   • Renal dysfunction 9

Clinical Manifestations of Hyponatremia

Symptoms vary based on severity:

• Mild (126-135 mEq/L): Often asymptomatic
• Moderate (120-125 mEq/L): Nausea, headache, confusion, muscle cramps
• Severe (<120 mEq/L): Seizures, coma, respiratory arrest, death 3

Management Considerations

1. For mild hyponatremia: Monitor and consider fluid restriction to 1,000 mL/day 1
2. For moderate to severe hyponatremia:
   • Consider discontinuation of the offending medication 3, 8
   • Implement more severe fluid restriction
   • Consider albumin infusion for severe cases 1
3. Correction rate: Should not exceed 8 mmol/L per day to prevent central pontine myelinolysis 9

Prevention and Monitoring

• High-risk patients (elderly, female, multiple risk factors) should have serum sodium checked within 2-4 weeks of starting at-risk medications 1, 7
• Patients on combination therapy (especially thiazide + SSRI) require closer monitoring 2
• Patient education about symptoms of hyponatremia and when to seek medical attention 1

Important Clinical Pitfalls

1. Delayed recognition: Symptoms of hyponatremia can be nonspecific and mistaken for the underlying condition being treated
2. Polypharmacy: Risk increases substantially with multiple at-risk medications
3. Rapid correction: Overly rapid correction of chronic hyponatremia can lead to osmotic demyelination syndrome
4. Seasonal variation: Risk may increase during hot weather due to increased sweating and fluid intake

Remember that hyponatremia is the most common electrolyte abnormality in hospitalized patients 10, and early recognition of drug-induced cases can significantly reduce morbidity and mortality.