What medications can cause hypernatremia?

Medications That Can Cause Hypernatremia

Vaptans (tolvaptan, conivaptan) are the most common medications that directly cause hypernatremia through their mechanism of action as selective vasopressin receptor antagonists. 1, 2

Mechanism-Based Classification of Medications Causing Hypernatremia

1. Direct Induction of Free Water Loss

• Vaptans (V2-receptor antagonists)

  • Tolvaptan and conivaptan block vasopressin receptors in the collecting ducts, causing selective water diuresis without electrolyte loss 1
  • Can cause rapid increases in serum sodium concentration when used inappropriately 2
  • Particular risk in patients with cirrhosis and ascites 1

• Loop Diuretics

  • Furosemide and other loop diuretics can cause hypernatremia by inducing excessive free water loss 1
  • Risk increases with high doses or continuous infusions 1
  • Particularly problematic when fluid replacement is inadequate 1

2. Medications That Impair Thirst or Water Access

• Sedatives and Antipsychotics

  • Can impair thirst sensation or ability to access water 3
  • Particularly risky in elderly or institutionalized patients 3

• Anticholinergic Medications

  • Can cause dry mouth and reduce fluid intake 4
  • Examples include tricyclic antidepressants and first-generation antihistamines 4

3. Medications That Affect Renal Water Handling

• Lithium

  • Can cause nephrogenic diabetes insipidus by reducing the kidney's response to vasopressin 5
  • Results in polyuria and potential hypernatremia if water intake is inadequate 5

• Demeclocycline

  • Tetracycline derivative that antagonizes ADH action in the kidney 1
  • Used therapeutically to treat SIADH but can cause hypernatremia as a side effect 1

High-Risk Clinical Scenarios

• Combination Diuretic Therapy

  • Using multiple diuretics together (loop diuretics, thiazides, potassium-sparing) increases risk 1
  • Particularly dangerous in patients with cirrhosis or heart failure 1

• Osmotic Agents

  • Mannitol, hypertonic saline, or excessive sodium bicarbonate administration can cause hypernatremia 6
  • Often seen in critical care settings 6

• Excessive Sodium Intake

  • Hypertonic saline solutions 3
  • Sodium bicarbonate administration 3
  • Sodium polystyrene sulfonate (used for hyperkalemia) 3

Monitoring and Prevention

• High-Risk Patient Populations

  • Elderly patients (impaired thirst mechanism) 3
  • Patients with impaired consciousness 6
  • Infants and children 1
  • Patients with cirrhosis or heart failure on diuretics 1

• Monitoring Recommendations

  • Check electrolytes within 1-2 weeks of starting vaptans 1
  • Monitor sodium levels closely when using multiple diuretics 1
  • Ensure adequate fluid intake in patients on medications that can cause hypernatremia 3

• Prevention Strategies

  • Ensure access to free water, especially in hospitalized or institutionalized patients 3
  • Start with lower doses of medications known to cause hypernatremia 1
  • Consider alternative medications in high-risk patients 4

Treatment Approach

• Acute Hypernatremia (<48 hours)

  • Can be corrected more rapidly (no more than 1 mEq/L/hour) 6
  • Consider hemodialysis for severe cases 6

• Chronic Hypernatremia (>48 hours)

  • Correct slowly at rate of 8-10 mmol/L/day maximum 6
  • Rapid correction can lead to cerebral edema 6

• Medication Management

  • Discontinue or reduce dosage of causative medication when possible 3
  • Replace free water losses with hypotonic fluids 3
  • Treat underlying condition (e.g., diabetes insipidus) 5

Remember that hypernatremia is less common than hyponatremia but carries significant morbidity and mortality, especially when severe or when corrected too rapidly 6, 3.