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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-24.

TABLE II-24. DIURETICS
DrugMaximum Adult Daily Dose (mg)DrugMaximum Adult Daily Dose (mg)
Carbonic anhydrase inhibitorsThiazides
 Acetazolamide1,000 Bendroflumethiazide5
 Methazolamide300 Chlorothiazide2,000
Loop diuretics  Chlorthalidone200
 Bumetanide10 Hydrochlorothiazide200
 Ethacrynic acid400 Indapamide5
 Furosemide600 Metolazone20
 Torsemide200
 Osmotic diuretics
 Mannitola200 g
Potassium-sparing diuretics
 Amiloride20
 Spironolactone400
 Triamterene300
 Eplerenone100

aNote: Mannitol doses >200 g/d or doses resulting in serum osmolality >320 mOsm/L can cause acute kidney injury.

Mechanism of Toxicity ⬆ ⬇

  1. Toxicity is associated with their pharmacologic effects, including promotion of fluid volume and electrolyte losses. Dehydration, hypokalemia (or hyperkalemia with spironolactone and triamterene), hypomagnesemia, hyponatremia, and hypochloremic alkalosis can occur. Electrolyte imbalance may lead to cardiac arrhythmias and may enhance digitalis toxicity. Diuretics are classified on the basis of the pharmacologic mechanisms by which they affect solute and water loss.
  2. Pharmacokinetics (see Table II-63)

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. 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 the onset of diuretic action. 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, rhabdomyolysis, and cardiac rhythm disturbances.
  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 cause excessive intravascular volume expansion and circulatory overload resulting in CHF or pulmonary edema. Rapid diuresis may result in fluid and electrolyte imbalances, dehydration and hypovolemia. Mannitol can also transiently increase the osmol gap.

Diagnosis ⬆ ⬇

Is based on a history of exposure and evidence of dehydration and acid-base or electrolyte imbalance. Note that patients on diuretics may also be taking other cardiac and antihypertensive medications.

  1. Specific levels are not routinely available or clinically useful.
  2. Other useful laboratory studies include electrolytes (including calcium and magnesium), glucose, BUN, creatinine, and ECG.

Treatment ⬆

  1. Emergency and supportive measures
    1. Replace fluid loss with IV crystalloid solutions and correct electrolyte abnormalities. Correction of diuretic-induced hyponatremia should be limited to 1-2 mEq/h to avoid osmotic demyelinating syndrome unless seizures or coma is present. In this case, 3% hypertonic saline should be used for a more rapid correction.
    2. Monitor the ECG until the serum potassium returns to normal.
  2. Specific drugs and antidotes. There are no specific antidotes.
  3. Decontamination. Administer activated charcoal orally if conditions are appropriate (see Table I-37). Gastric lavage is not necessary after small-to-moderate ingestions if activated charcoal can be given promptly. Cathartics have not been shown to be beneficial in preventing absorption and may worsen dehydration.
  4. Enhanced elimination. No experience with extracorporeal removal of diuretics has been reported.