What medications can cause hypokalemia and hyponatremia?

Medications That Can Cause Hypokalemia and Hyponatremia

Diuretics are the most common medications that cause both hypokalemia and hyponatremia, particularly thiazide diuretics and loop diuretics. These medications are primary culprits for dual electrolyte abnormalities due to their mechanisms of action in the kidneys.

Diuretics That Cause Both Hypokalemia and Hyponatremia

Thiazide and Thiazide-like Diuretics

• Chlorthalidone: Causes hypokalemia through increased sodium delivery to distal tubules and secondary hyperaldosteronism. Associated with higher risk of hyponatremia compared to other diuretics 1
• Hydrochlorothiazide: One of the most common causes of drug-induced hyponatremia 1, 2
• Indapamide: Can cause severe hyponatremia (plasma sodium as low as 103-104 mmol/L) and severe hypokalemia (plasma potassium as low as 1.6-2.2 mmol/L) 3
• Metolazone: Similar mechanism to other thiazides 4

Loop Diuretics

• Furosemide: Inhibits sodium and chloride reabsorption in the ascending limb of the loop of Henle, causing hypokalemia and potentially hyponatremia 4, 5
• Bumetanide: Similar mechanism to furosemide 4
• Torsemide: Similar mechanism to other loop diuretics 4

Mechanisms of Electrolyte Disturbances

Hypokalemia Mechanisms

1. Increased distal tubular flow: Diuretics increase delivery of sodium to distal tubules, enhancing sodium-potassium exchange 6
2. Secondary hyperaldosteronism: Volume contraction stimulates aldosterone secretion, which promotes sodium reabsorption and potassium excretion 6
3. Duration of effect: Potassium loss may exceed the period of diuresis, as elevated aldosterone levels can persist for 24+ hours 6

Hyponatremia Mechanisms

1. Impaired urinary dilution: Thiazides impair the kidney's ability to excrete free water
2. Increased ADH secretion: Volume depletion stimulates antidiuretic hormone release
3. Direct effect on renal tubules: Alters sodium handling in distal tubules

Risk Factors for Diuretic-Induced Electrolyte Abnormalities

• Age: Elderly patients are more susceptible
• Gender: Females are at higher risk for hyponatremia 1
• Low body weight
• Concomitant medications: ACE inhibitors, ARBs, NSAIDs 7
• Reduced renal function
• Liver disease: Especially cirrhosis 4
• High-dose diuretic therapy
• Low sodium intake

Other Medications That Can Cause Hypokalemia

1. Corticosteroids: Cause potassium loss through mineralocorticoid effects 5
2. ACTH: Similar mechanism to corticosteroids 5
3. Amphotericin B: Causes renal tubular damage
4. Aminoglycosides: Can cause renal potassium wasting
5. Beta-agonists (e.g., albuterol): Shift potassium intracellularly
6. Theophylline: Can lower serum potassium levels 7
7. Insulin: Shifts potassium intracellularly
8. Laxatives (with chronic abuse): Cause intestinal potassium loss 7

Other Medications That Can Cause Hyponatremia

1. Antidepressants: Particularly SSRIs and SNRIs 2
2. Antiepileptic drugs: Carbamazepine, oxcarbazepine 2
3. Antipsychotics: Particularly first-generation agents
4. Proton pump inhibitors: Less commonly 2
5. Chemotherapeutic agents: Cyclophosphamide, vincristine
6. Opioids: Through SIADH-like mechanism
7. NSAIDs: Can potentiate ADH effects

Monitoring and Prevention

1. Baseline electrolyte measurement before starting diuretics
2. Regular monitoring:
   • Check electrolytes within 2-4 weeks after starting therapy 1
   • More frequent monitoring in high-risk patients
3. Dose adjustment: Use lowest effective dose
4. Combination strategies:
   • Combine thiazide or loop diuretics with potassium-sparing diuretics (spironolactone, amiloride, triamterene) 4
   • Be cautious with spironolactone as it can cause hyperkalemia 8

Clinical Presentation of Electrolyte Abnormalities

Hypokalemia Symptoms

• Muscle weakness or cramps
• Fatigue
• Cardiac arrhythmias
• Metabolic alkalosis

Hyponatremia Symptoms

• Headache, difficulty concentrating
• Confusion, memory impairment
• Weakness, unsteadiness
• Severe cases: hallucinations, seizures, coma 1

Management Considerations

1. For mild electrolyte abnormalities: Consider dose reduction
2. For moderate abnormalities: Consider drug discontinuation or substitution
3. For severe abnormalities: Discontinue the offending drug and correct electrolytes 1
4. Temporary diuretic discontinuation during periods of decreased oral intake, vomiting, or diarrhea 1

By understanding which medications can cause these electrolyte abnormalities and implementing appropriate monitoring strategies, clinicians can minimize the risk of serious complications from hypokalemia and hyponatremia.