Metolazone
Indication
Metolazone is used in the treatment of mild to moderate hypertension. It is also commonly used in conjunction with a loop diuretic in the management of edema secondary to CHE. Additionally, metolazone is used for the treatment of edema caused by nephrotic syndrome and in postoperative cardiac surgical patients.
Mechanism of Action
Metolazone is a thiazide-type diuretic whose primary site of action is the distal convoluted tubule and whose secondary site of action is the proximal tubule. In
these regions, metolazone inhibits sodium reabsorption, causing increased excretion of sodium and water as well as potassium and hydrogen ions.
Dosing
Metolazone is only available for oral/enteral administration.
Children: 0.2 to 0.4 mg/kg/day divided every 12 to 24 hours
Adults:
Edema: 5 to 20 mg/dose every 24 hours
Hypertension: 2.5 to 5 mg/dose every 24 hours
Pharmacokinetics
Metolazone has an onset of action of approximately 1 hour and a duration of action of 12 to 24 hours. Oral absorption of the drug is dependent on the preparation used, and protein binding is 95%. The half-life is 6 to 20 hours and 70 to 95% of the drug is eliminated unchanged in the urine.
Monitoring parameters: serum electrolytes, blood pressure, blood urea nitrogen, Cr, fluid balance
Contraindications: anuria, allergy to thiazide diuretics or sulfonamides, hepatic coma
Precautions/Adverse Effects
Use cautiously in patients with severe renal disease, reduced hepatic function, diabetes mellitus, systemic lupus erythematosus, gout, and in patients with high triglyceride or cholesterol levels.
Common adverse reactions with metolazone use include palpitations, chest pain, hypotension, headaches, drowsiness, rash, and GI irritation. Hypokalemia, hyponatremia, hypochloremia, metabolic alkalosis, hyperglycemia, thrombocytopenia, leukopenia, aplastic anemia, and hyperuricemia have also been reported. Patients may experience sensitivity to light, chills, and abdominal bloating.
Poisoning Information
Metolazone overdose is commonly characterized by orthostatic hypotension, dizziness, drowsiness, fainting, and volume depletion. Treatment is supportive and symptomatic and replacement of fluid and electrolyte losses maybe necessary.
Drug-Drug Interactions
With metolazone use, there is a decreased antihypertensive effect with NSAIDs. There are also increased potassium losses with steroids and amphotericin B; and increased hypersensitivity reactions to allopurinol. There is increased incidence of digoxin toxicity caused by hypokalemia and hypomagnesemia.
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