CHAPTER 2-64: DIURETICS

INTRODUCTION

Diuretics are prescribed commonly for the management of essential hypertension, congestive heart failure, ascites, and chronic renal insufficiency. Adverse effects from chronic use or misuse (in sports, dieting, and anorexia) are more frequently encountered than those from acute overdose. Overdoses are generally benign, and no serious outcomes have resulted from acute ingestion. Common currently available diuretics are listed in Table II–25.

MECHANISM OF TOXICITY

1. The toxicity of these drugs is associated with their pharmacologic effects, which decrease fluid volume and promote electrolyte loss; these include dehydration, hypokalemia (or hyperkalemia with spironolactone and triamterene), hypomagnesemia, hyponatremia, and hypochloremic alkalosis. Electrolyte imbalance may lead to cardiac arrhythmias and may enhance digitalis toxicity (Digoxin and other Cardiac Glycosides). Diuretics are classified on the basis of the pharmacologic mechanisms by which they affect solute and water loss (see Table II–25).

2. Pharmacokinetics (see Table II–66)

TOXIC DOSE

Minimum toxic doses have not been established. Significant dehydration or electrolyte imbalance is unlikely if the amount ingested is less than the usual recommended daily dose (see Table II–25). High doses of intravenous ethacrynic acid and furosemide can cause ototoxicity, especially when administered rapidly and to patients with renal failure.

CLINICAL PRESENTATION

Gastrointestinal symptoms including nausea, vomiting, and diarrhea are common after acute oral overdose. Lethargy, weakness, hyporeflexia, and dehydration (and occasionally hypotension) may be present if volume loss and electrolyte disturbances are present, although the onset of symptoms may be delayed for 2–4 hours or more until diuretic action is obtained. Spironolactone is very slow, with maximal effects after the third day.

1. Hypokalemia may cause muscle weakness, cramps, and tetany. Severe hypokalemia may result in flaccid paralysis and rhabdomyolysis. Cardiac rhythm disturbances may also occur.

2. Spironolactone and other potassium-sparing agents may cause hyperkalemia and hyperchloremic metabolic acidosis, especially in patients with renal insufficiency.

3. Hypocalcemia and hypomagnesemia may also cause tetany.

4. Hyponatremia, hyperglycemia, hypercalcemia, and hyperuricemia may occur, especially with thiazide diuretics.

5. Carbonic anhydrase inhibitors may induce metabolic acidosis. Drowsiness and paresthesias are commonly seen in renal insufficiency or the elderly.

6. Rapid administration of mannitol (an osmotic diuretic) may ...