Hydrochlorothiazide

Hydrochlorothiazide (HCTZ or HCT) is a diuretic medication often used to treat high blood pressure and swelling due to fluid build up. Other uses include diabetes insipidus, renal tubular acidosis, and to decrease the risk of kidney stones in those with high calcium level in the urine. For high blood pressure it is often recommended as a first line treatment.

Molecular Structure

Hydrochlorothiazide

Class of Drug

Thiazide diurectic.

Mechanism of Action

Inhibits sodium resorption in distal tubule, resulting in increased urinary excretion of sodium, potasssium, and water.

Indications / Dosage / Route

Routes of Administration: Oral only.

Condition: Edema (adjunct for edema associated with CHF, hepatic cirrhosis, corticosteroid or estrogen therapy)

Dose: Adults: 25-100 mg/d as single or divided doses.

Condition: Hypertension

Dose: Adults: Initial: 25 mg/d as single dose. Increase 50 mg/d in single or 2 divided doses. Maximum: 50 mg.

         Children: 2-12 years: 37.5-100 mg/d in 2 divided doses.

Children <2 years: 12.5-37.5 mg/d in 2 divided doses.

Adjustment of Dosage

Kidney disease: Use with caution. Ineffective in severe renal failure.

Liver disease: Use with caution. May cause electrolyte imbalance.

Elderly: Use with caution because of age-related impairment of kidney function.

Pediatric: See above.

Onset of Action Peak Effect Duration
Diuretic <2 h 4 h 16-12 h

Food and Drug Interactions

Food: Should be taken with food.

Pregnancy: Category D.

Lactation: Excreted in breast milk. Considered compatible by American Academy of Pediatrics. Thiazide diuretics may suppress lactation.

Contraindications: Anuria, hypersensitivity to thiazides or sulfonamide derived drugs.

Warnings / Precautions

> Use with caution in patients with the following conditions: severe renal or liver disease, systemic lupus erythematosus, patients receiving lithium concurrently, and in jaundiced infants (risk of hyperbilirubinemia).

> Consider reducing dose of other antihypertensive drug if a thiazide is added to the regimen.

> A potassium supplement should be administered only when diet alone is inadequate. Provide patient with list of potassium rich foods: citrus juices, grape, apple or cranberry juices, bananas, tomatoes, apricots, dates, fish, cereals. If a potassium supplement is needed, the liquid preparation should be used rather than tablets.

> Discontinue drug prior to parathyroid function tests as thiazides raise serum calcium.

> Be aware that elderly patients may experience significant orthostatic hypotension, in particular after a meal.

> Consider using an alternative drug if the patient has significant hyperlipidemia.

> Hypersensitivity reactions may occur even if there is no previous history of allergy or bronchial asthma.

> A thiazide may exacerbate or activate systemic lupus erythematosus.

Clinically Important Drug Interactions

> Drugs that increase effects/toxicity of thiazides: alcohol, barbiturates, narcotics, other antihypertensive drugs, glucocorticoids.

> Drugs that decrease effects/toxicity of thiazides: cholestyramine, colestipol, NSAfDs.

> Thiazides increase effects/toxicity of digitalis glycosides, lithium, corticosteroids, nondepolarizing muscle relaxants (curare type drugs).

> Thiazides decrease effects/toxicity of sulfonylureas, insulin.

Adverse Reactions

> Common: None.

> Serious: hypokalemia, bone marrow suppression, hypotension, hyponatremia, orthostatic hypotension, hypocalcemia, hypomagnesemia, aplastic anemia, hemolytic anemia, uremia, hypersensitivity reactions.

Parameters to Monitor

> Serum electrolytes including sodium, potassium, glucose, BUN, creatinine, uric acid, bicarbonate.

> Feet, legs, and sacral area for edema; this should be done on a daily basis.

> If the patient is also taking digitalis, monitor serum digoxin levels and signs of digitalis toxicity (vomiting, muscle cramps, confusion).

> BP before and periodically after administration.

> Signs and symptoms of hypokalemia, particularly in the elderly, the debilitated, and those with edema: dry mouth, anorexia, nausea, vomiting, thirst, mental confusion, paralytic ileus, muscle cramps, cardiac arrhythmias, depressed reflexes. If hypokalemia develops, administer potassium sparing diuretic or potassium supplement

> Kidney function. Serum electrolytes, BUN, creatinine, uric acid, blood sugar, should be determined weekly at beginning of therapy. For patients on long-term therapy, these determinations should be made q6-8mon.

> Intake of fluids and urinary and other fluid output to minimize renal toxicity. Increase fluid intake if inadequate. Closely monitor electrolyte levels.

> Monitor electrolyte imbalance as a result of excessive diuresis or oliguria.

> Evaluate patient for orthostasis with BP measurements in the sitting, lying, and standing positions repeatedly before and after initiating therapy.

> Therapeutic efficacy. Weigh patient before breakfast and immediately before voiding. This should be done at the same time each day and with the same clothing. Other indications of efficacy: increased urine output reduction of edema with weight loss, con¬trol of hypertension, adequate tissue perfusion (warm, dry skin).

> Skin and mucous membranes for signs of petechiae for those receiving large doses of the drug or for extended periods.

> For diabetic or diabetic prone patients: Monitor blood glucose for hyperglycemia and adjust dose if necessary. Hyper¬glycemia is usually not a problem unless high doses of drug are used.

> Signs of hyperuricemia.

> Symptoms of CHF.

Advice to Patient

> Take this drug in the morning to avoid nocturia.

> Change position slowly, in particular from recumbent to upright, to minimize orthostatic hypotension. Sit at the edge of the bed for several minutes before standing and lie down if feeling faint or dizzy. Avoid hot showers or baths and standing for long periods. Male patients should sit on the toilet while urinating rather than standing.

> Avoid drinking alcoholic beverages as these may exacerbate orthostatic hypotension.

> Do not engage in unaccustomed strenuous exercise without consulting treating physician.

> Do not drink large quantities of xanthine containing liquids: regular coffee, tea, or cocoa.

> Eat limited quantities of foods containing large amounts of sodium: beer, pretzels, luncheon meats, snack foods, bacon, Chinese foods, tomato juice, prepared soups.

> Use salt substitute rather than regular salt.

> Take OTC drugs only after consulting with physician as many of these contain large amounts of sodium.

Further Useful Info

> Hydrochlorothiazide is the diuretic of choice for patients with the following conditions: mild to moderate hypertension, asthma, COPD, hypertension in patients with urinary calcium calculi, CHF in patients with hypertension.

> Thiazides are often used in combination therapy with many other antihypertensive drugs including P blockers, ACE inhibitors, angiotensin receptor blockers, and potassium sparing diuretics.

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