Microzide (Hydrochlorothiazide, HCTZ)
HydroDIURIL® , Microzide® , Oretic® | Esidrix® | Ezide™ | HCT 50™ | Hydrocot™ | HydroKraft™
Classification:
Cardiovascular Agents
Electrolytic and Renal Agents
Description: Hydrochlorothiazide (HCTZ) is a thiazide diuretic used in the management of edema and hypertension. In hypertension, thiazide diuretics are often used as initial therapy, either alone or in combination with other agents. Unlike the loop diuretics, their efficacy is diminished in patients with renal insufficiency. Hydrochlorothiazide also has been used to treat diabetes insipidus and hypercalciuria, although these are not FDA-approved indications. Hydrochlorothiazide was approved by the FDA in 1959.
Mechanism of Action: Thiazide diuretics increase the excretion of sodium, chloride, and water by inhibiting sodium ion transport across the renal tubular epithelium. Although thiazides may have more than one action, the major mechanism responsible for diuresis is to inhibit active chloride reabsorption at the distal portion of the ascending limb or, more likely, the early part of the distal tubule (i.e., the cortical diluting segment). Exactly how chloride transport is impaired is unknown. Thiazides also increase the excretion of potassium and bicarbonate, and they decrease the urinary excretion of calcium and uric acid. Hydrochlorothiazide may be used to reduce hypercalciuria and prevent the recurrence of calcium-containing renal calculi. By increasing the sodium load at the distal renal tubule, hydrochlorothiazide indirectly increases potassium excretion via the sodium-potassium exchange mechanism. Hypochloremia and hypokalemia can cause mild metabolic alkalosis. The diuretic efficacy of hydrochlorothiazide is not affected by the acid-base balance of the patient. Hydrochlorothiazide is not an aldosterone antagonist, and its main action is independent of carbonic anhydrase inhibition.
The antihypertensive mechanism of hydrochlorothiazide is unknown. It usually does not affect normal blood pressure. Initially, diuretics lower blood pressure by decreasing cardiac output and reducing plasma and extracellular fluid volume. Cardiac output eventually returns to normal, plasma and extracellular fluid values return to slightly less than normal, but peripheral vascular resistance is reduced, resulting in lower blood pressure. These diuretics also decrease the glomerular filtration rate, which contributes to the drug’s lower efficacy in patients with renal impairment. The changes in plasma volume induce an elevation in plasma renin activity, and aldosterone secretion is increased, contributing to the potassium loss associated with thiazide diuretic therapy. In general, diuretics worsen LVH and glucose tolerance, and exert detrimental effects on the lipid profile.
Pharmacokinetics: Hydrochlorothiazide is administered orally. The onset of action of the drug is 2 hours following oral administration, with peak effects occurring at 4 hours. The duration of action ranges from 6 - 12 hours. Hydrochlorothiazide absorption from the GI tract varies depending on the formulation and dose. Bioavailability is approximately 50 - 60%. The drug crosses the placenta but not the blood-brain barrier and is distributed in breast milk. Hydrochlorothiazide is not significantly metabolized and is excreted unchanged in the urine. The elimination half-life of hydrochlorothiazide was originally reported to range from 5.6 - 14.8 hours when plasma levels were followed for at least 24 hours. A more recent study reports a mean elimination half-life of 2.5 hours in patients with normal renal function. The elimination half-life is estimated to increase to 12 - 20 hours in patients with severe renal disease (e.g. CrCl < 10 ml/min).
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[ Revised 9/27/2005 12:04:00 PM ]
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