Drug-Induced Hyponatremia

Hyponatremia is an electrolyte disturbance characterized by a sodium concentration in the plasma below 135 mmol/L. At lower levels, overhydration (water intoxication), an urgently dangerous condition, may result.

Severe hyponatremia can cause an osmotic transfer of water from the plasma into the brain cells. Most body cells can expand as they take on water, but brain cells are confined in the skull. The following symptoms may therefore begin to be experienced as brain cells take on water:

  • Nausea (which stimulates the release of antidiuretic hormone [ADH], which promotes the retention of water, and creates a positive feedback loop)
  • Headache
  • Vomiting
  • Malaise

As the hyponatremia worsens, symptoms may include:

  • Diminished reflexes
  • Confusion
  • Convulsions
  • Stupor
  • Coma

Hyponatremia can occur in isolation or as a complication of another illness and is commonly associated with the use of certain medications, including:

  • Hormone analog - desmopressin (DDAVP, Stimate, Minirin), oxytocin
  • Diuretics - indapamide, chlorothiazide, frusemide
  • Selective Serotonin Reuptake Inhibitors (SSRIs)
  • MAOI - modobemide
  • Antipsychotics - dozapine
  • Antiepileptics - carbamazepine
  • ACE inhibitors - enalapril, captopril
  • COX-2 inhibitors - celecoxib
  • Hypnotics - temazepam
  • Chemotherapeutics - vincristine, vinplastine, carboplatin, cisplatin, cydophosphamine
  • Sulfonylurea - glipizide, glimepiride, glibenclamide, gliclazide
  • Proton pump inhibitors - omeprazole, pantoprazole
  • Desmopressin

Although drugs are a common cause of hyponatremia, other causes should be considered. To find the cause, it may be helpful to assess the fluid status and plasma osmonality of the patient.

Because, on average, the elderly take more medications, as our population ages the incidence of drug-induced hyponatremia will likely increase.

Drug-induced hyponatremia is generally asymptomatic, so it is usually diagnosed incidentally after routine blood tests. In mild cases, it may be sufficient to withdraw the drug and keep the patient under observation. More severe cases may additionally require short-term fluid restriction. Acute cases, or those with severe or refractory (not responding to treatment) hyponatremia may need to be referred.