Diuretic – Antihypertensive
Action And Clinical Pharmacology: Hydrochlorothiazide is a diuretic and antihypertensive. Hydrochlorothiazide interferes with the renal tubular mechanism of electrolyte reabsorption. It increases excretion of sodium and chloride in approximately equivalent amounts. Natriuresis may be accompanied by some loss of potassium, magnesium and bicarbonate. Urinary calcium excretion may be decreased. While this compound is predominantly a saluretic agent, in vitro studies have shown that it has a carbonic anhydrase inhibitory action which seems to be relatively specific for the renal tubular mechanism. It does not appear to be concentrated in erythrocytes or the brain in sufficient amounts to influence the activity of carbonic anhydrase in those tissues.
Hydrochlorothiazide is useful in the treatment of hypertension. It may be used alone or as an adjunct to other antihypertensive drugs. Hydrochlorothiazide does not usually affect normal blood pressure. The mechanism of its antihypertensive action is not known.
Indications And Clinical Uses: Edema associated with congestive heart failure, hepatic cirrhosis, in drug-induced edema (corticosteroid and estrogen therapy), nephrotic syndrome, acute glomerulonephritis, and chronic renal failure.
Hypertension may be used alone or in combination with other antihypertensive drugs. Since it enhances the action of these agents, their dosage must be reduced to avoid an excessive drop in pressure and other unwanted side effects.
Contra-Indications: Anuria. If increasing azotemia and oliguria occur during treatment of severe progressive renal disease, the diuretic should be discontinued. Hydrochlorothiazide is contraindicated in persons known to be sensitive to any component of this product or to other sulfonamide-derived drugs. See Warnings, Pregnancy and Lactation.
Manufacturers’ Warnings In Clinical States: Impaired Renal Function and/or Azotemia: When creatinine clearance falls below 30 mL/min thiazide diuretics are ineffective.
Azotemia may be precipitated or increased by hydrochlorothiazide. Cumulative effects of the drug may develop in patients with impaired renal function. If increasing azotemia and oliguria occur during treatment of renal disease the diuretic should be discontinued.
Hepatic Disease: Thiazides should be used with caution in patients with impaired hepatic function or progressive liver disease, since minor alterations of fluid and electrolyte balance, may precipitate hepatic coma.
Metabolic: Hyperuricemia may occur or gout may be precipitated in certain patients receiving thiazide therapy.
Thiazide therapy may impair glucose tolerance. Dosage adjustment of antidiabetic agents, including insulin, may be required.
Increases in cholesterol and triglyceride levels may be associated with thiazide diuretic therapy.
Nonspecific small bowel lesions consisting of stenosis with or without ulceration, may occur in association with the administration of enteric-coated potassium salts, alone or with oral diuretics. These small bowel lesions have caused obstruction, hemorrhage and perforation. Surgery was frequently required and deaths have occurred. Available information tends to implicate enteric-coated potassium salts, although lesions of this type also occur spontaneously. Such preparations should be used only when adequate dietary supplementation is not practical, and should be discontinued immediately if abdominal pain, distention, nausea, vomiting or gastrointestinal bleeding occur.
Other: Sensitivity reactions may occur in patients with or without a history of allergy or bronchial asthma.
The possibility of exacerbation or activation of systemic lupus erythematosus has been reported.
Pregnancy: The routine use of diuretics in otherwise healthy pregnant women with or without mild edema is not recommended and exposes mother and fetus to unnecessary hazard. Diuretics do not prevent development of toxemia of pregnancy and there is no satisfactory evidence that they are useful in the treatment of toxemia.
Thiazides cross the placental barrier and appear in cord blood. When hydrochlorothiazide is used in pregnancy or in women of childbearing age, the potential benefits of the drug should be weighed against the possible hazards to the fetus. These hazards include fetal or neonatal jaundice, thrombocytopenia, and possibly other adverse reactions which have occurred in the adult.
Lactation: Thiazides appear in breast milk. If use of the drug is deemed essential, the patient should stop nursing.
Precautions: Electrolyte Imbalance: Careful check should be kept for signs of fluid and electrolyte imbalance namely, hyponatremia, hypochloremic alkalosis, hypokalemia, and hypomagnesemia. Serum and urine electrolyte determinations are particularly important when the patient is vomiting excessively or receiving parenteral fluids. Warning signs or symptoms of fluid and electrolyte imbalance include: dryness of mouth, thirst, weakness, lethargy, drowsiness, restlessness, seizures, confusion, muscle pains or cramps, muscular fatigue, hypotension, oliguria, tachycardia, and gastrointestinal disturbances such as nausea and vomiting.
Hypokalemia may develop with hydrochlorothiazide as with any other potent diuretic, especially with brisk diuresis, after prolonged therapy or when severe cirrhosis is present. Hypokalemia can sensitize or exaggerate the response of the heart to the toxic effects of digitalis (e.g., increased ventricular irritability).
Although any chloride deficit is generally mild and usually does not require specific treatment except under extraordinary circumstances (as in liver disease or renal disease), chloride replacement may be required in the treatment of metabolic alkalosis.
Diuretic induced hyponatremia is usually mild and asymptomatic. In a few patients, hyponatremia may become severe and symptomatic. Such patients require immediate attention and appropriate treatment.
Dilutional hyponatremia may occur in edematous patients in hot weather; appropriate therapy is water restriction, rather than administration of salt except in rare instances when the hyponatremia is life threatening. In actual salt depletion, appropriate replacement is the therapy of choice.
The antihypertensive effect of the drug may be enhanced in the postsympathectomy patient.
Thiazides may decrease serum PBI levels without signs of thyroid disturbance.
Thiazides may decrease urinary calcium excretion. Thiazides may cause intermittent and slight elevation of serum calcium in the absence of known disorders of calcium metabolism. Thiazides should be discontinued before carrying out tests for parathyroid function.
Drug Interactions: When given concurrently, the following drugs may interact with thiazide diuretics.
Alcohol, barbiturates or narcotics: Potentiation of orthostatic hypotension may occur.
Antidiabetic drugs (oral agents and insulin): Dosage adjustment of the antidiabetic drug may be required.
Other antihypertensive drugs: Additive effect. Diuretic therapy should be discontinued for 2 to 3 days prior to initiation of therapy with an ACE inhibitor to reduce the likelihood of first dose hypotension.
Cholestyramine and colestipol resins: Absorption of hydrochlorothiazide is impaired in the presence of anionic exchange resins. Single doses of either cholestyramine or colestipol resins bind the hydrochlorothiazide and reduce its absorption from the gastrointestinal tract by up to 85% and 43% respectively.
Corticosteroids, ACTH: intensified electrolyte depletion, particularly hypokalemia.
Pressor amines (e.g., adrenaline): Possible decreased response to pressor amines but not sufficient to preclude their use.
Skeletal muscle relaxants, nondepolarizing (e.g., tubocurarine): Possible increased responsiveness to the muscle relaxant.
Lithium: Diuretic agents reduce the renal clearance of lithium and add a high risk of lithium toxicity; concomitant use is not recommended. Refer to the Product Monographs for lithium preparations before use of such preparations.
NSAIDs: In some patients, the administration of a NSAIDs can reduce the diuretic, natriuretic, and antihypertensive effects of diuretics.
Drug/Laboratory Test Interactions : Because of their effects on calcium metabolism, thiazides may interfere with tests for parathyroid function (see Precautions).
Adverse Reactions: Gastrointestinal: anorexia, gastric irritation, nausea, vomiting, cramping, diarrhea, constipation, jaundice (intrahepatic cholestatic jaundice), pancreatitis, sialoadenitis.
CNS: dizziness, vertigo, paresthesias, headache, xanthopsia.
Hematologic: leukopenia, agranulocytosis, thrombocytopenia, aplastic anemia, hemolytic anemia.
Cardiovascular: hypotension, including orthostatic hypotension.
Hypersensitivity: purpura, photosensitivity, rash, urticaria, necrotizing angiitis (vasculitis, cutaneous vasculitis), fever, respiratory distress, including pneumonitis and pulmonary edema, anaphylactic reactions, toxic epidermal necrolysis.
Metabolic: hyperglycemia, glycosuria, hyperuricemia, electrolyte imbalance, including hyponatremia and hypokalemia.
Renal: renal dysfunction, interstitial nephritis, renal failure.
Other: muscle spasm, weakness, restlessness, transient blurred vision.
Symptoms And Treatment Of Overdose: Symptoms and Treatment: The most common signs and symptoms observed are those caused by electrolyte depletion (hypokalemia, hypochloremia, hyponatremia) and dehydration resulting from excessive diuresis. If digitalis has also been administered, hypokalemia may accentuate cardiac arrhythmias.
In the event of overdosage, symptomatic and supportive measures should be employed. If ingestion is recent, emesis should be induced or gastric lavage performed. Dehydration, electrolyte imbalance, hepatic coma and hypotension should be corrected by established procedures. If required, give oxygen or artificial respiration for respiratory impairment.
Dosage And Administration: Therapy should be individualized according to patient response. Use the smallest dosage necessary to achieve the required response.
Adults: Edema: The usual starting dosage is 25 to 100 mg a day given in a single dose or in 2 divided doses. Many patients respond to intermittent therapy (administration on alternate days or on 3 to 5 days each week) which may avoid an excessive response and undesirable electrolyte imbalance.
The maximum recommended daily dosage is 100 mg.
Hypertension: The usual starting dosage is 25 mg a day as a single or divided dose.
In some patients, when hydrochlorothiazide is given as a single entity or in combination with other antihypertensive agents, a starting dose of 12.5 mg daily may be sufficient. Dosage should be adjusted according to blood pressure response.
The maximum recommended daily dosage is 50 mg.
When thiazides are used with other antihypertensives, the dose of the latter may need to be reduced to avoid excessive decrease in blood pressure.
Infants and Children: The usual pediatric dosage is 2.5 mg/kg of body weight/day in 2 doses. Infants under 6 months of age may require up to 3.5 mg/kg/day in 2 doses.
On this basis, infants up to 2 years of age may be given 12.5 to 37.5 mg daily in 2 doses. Children from 2 to 12 years of age may be given 37.5 to 100 mg daily in 2 doses. Dosage in both age groups should be based on body weight.
Availability And Storage: 25 mg: Each flat, peach, compressed tablet, with bevelled edge, scored on one side and coded MSD 42 on the other, contains: hydrochlorothiazide 25 mg. Nonmedicinal ingredients: calcium phosphate dibasic, cornstarch, lactose, magnesium stearate and sunset yellow. Gluten- and tartrazine-free. Bottles of 100.
50 mg: Each flat, peach, compressed tablet, with bevelled edge, scored on one side and coded MSD 105 on the other, contains: hydrochlorothiazide 50 mg. Nonmedicinal ingredients: calcium phosphate dibasic, cornstarch, lactose, magnesium stearate and sunset yellow. Gluten- and tartrazine-free. Bottles of 100.
Store at 15 to 30°C.
HydroDIURIL® MSD Hydrochlorothiazide Diuretic – Antihypertensive