Hydrochlorothiazide
Indication
Hydrochlorothiazide is used in the treatment of mild to moderate hypertension. Additionally, hydrochlorothiazide is used for the treatment of edema caused by congestive heart failure, bronchopulmonary dysplasia, or nephrotic syndrome.
Mechanism of Action
Hydrochlorothiazide is a thiazide diuretic whose primary site of action is the distal convoluted tubule and secondary site of action is the proximal tubule.6 In these regions, the drug inhibits sodium reabsorption, causing increased excretion of sodium and water as well as potassium, bicarbonate, magnesium, phosphate, and calcium (transiently).
Dosing
Neonates and infants younger than 6 months:
Oral: 2 to 4 mg/kg/day in one to two doses; maximum daily dose, 37.5 mg
Infants older than 6 months and children:
Oral: 2 mg/kg/day in one to two doses; maximum daily dose, 200 mg
Adults:
Oral: 12.5 to 100 mg/day in one to two doses; maximum, 200 mg/day
Note Daily dosages should be decreased if used with other antihypertensive agents
Pharmacokinetics
Hydrochlorothiazide has an onset of action within 2 hours of oral administration, with a duration of action of 6 to 12 hours. The oral absorption in the
GI tract is approximately 60 to 80%. The half-life of hydrochlorothiazide is 5 to 15 hours, and hydrochlorothiazide is eliminated almost completely via the kidneys as unchanged drug.
Monitoring parameters: serum electrolytes, blood pressure, blood urea nitrogen, Cr, fluid balance
Contraindications: anuria; thiazide or sulfonamide allergy
Precautions/Adverse Effects
Use cautiously in patients with severe renal disease, reduced hepatic function, diabetes mellitus, systemic lupus erythematosus, and gout.
Adverse side effects of hydrochlorothiazide may include drowsiness, paresthesia, hypokalemia, hyponatremia, hypochloremic metabolic alkalosis, hyperglycemia, nausea, vomiting, anorexia, pancreatitis, cholestasis, hypotension, agranulocytosis, thrombocytopenia, leukopenia, prerenal azotemia, polyuria, and photosensitivity.
Poisoning Information
The most likely manifestations of hydrochlorothiazide overdose are lethargy, confusion, hypermotility, and muscle weakness. Treatment is supportive and symptomatic.
Drug-Drug Interactions
With hydrochlorothiazide use, there is a decreased antihypertensive effect with NSAIDS. With hydrochlorothiazide use, there are increased potassium losses with steroids and amphotericin B; and increased hypersensitivity reactions to allopurinol. With hydrochlorothiazide use, there is increased hyperglycemia with diazoxide; a decreased effectiveness of antidiabetic agents; a decreased clearance of lithium; increased hypotension with angiotensin-converting enzyme inhibitors; and increased renal toxicity with cyclosporine.
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