For the treatment of hypertension
Thiazides such as hydrochlorothiazide promote water loss from the body (diuretics). They inhibit Na+/Cl- reabsorption from the distal convoluted tubules in the kidneys. Thiazides also cause loss of potassium and an increase in serum uric acid. Thiazides are often used to treat hypertension, but their hypotensive effects are not necessarily due to their diuretic activity. Thiazides have been shown to prevent hypertension-related morbidity and mortality although the mechanism is not fully understood. Thiazides cause vasodilation by activating calcium-activated potassium channels (large conductance) in vascular smooth muscles and inhibiting various carbonic anhydrases in vascular tissue.
Adult: Initially, 12.5mg daily. Usual dose: 25-50 mg daily, either alone or combined w/ other antihypert ensives, up to 100 mg daily, if necessary.
Alcohol, barbiturates or narcotics: Co-administration may potentiate orthostatic hypotension. Oral and parenteral antidiabetic drugs may require adjustment of dosage with concurrent use. Other antihypertensive drugs may have an additive effect. Discontinuation of diuretic therapy 2-3 days before the initiation of treatment with an ACE inhibitor may reduce the likelihood of first-dose hypotension. The antihypertensive effect of the drug may be enhanced in the post-sympathectomy patient.
Cholestyramine and colestipol resin: Absorption of hydrochlorothiazide is impaired in the presence of anionic exchange resin. 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 or ACTH may intensify any Thiazide-induced electrolyte depletion, particularly hypokalaemia. Pressor amines such as adrenaline may show decreased arterial responsiveness when used with hydrochlorothiazide, but this reaction is not enough to preclude their therapeutic usefulness. Non-depolarising muscle relaxants such as tubocurarine may possibly interact with Hydrochlorothiazide to increase muscle relaxation. Non-steroidal anti-inflammatory drugs may attenuate the diuretic and antihypertensive effects of diuretics.
Drug/laboratory tests: Because thiazides may affect calcium metabolism, Hydrochlorothiazide may interfere with tests for parathyroid function.
Severe hepatic & renal impairment, Addison’s disease, preexisting hypercalcaemia, anuria, suiphonamide allergy. Pregnancy, lactation.Existing electrolyte disturbances, hepatic cirrhosis, severe heart failure, oedema, elderly, renal impairment. Monitor for signs of fluid & electrolyte disturbance. Heatic imoairment, DM, gout, hyperlipidaemia, hypercalcaemia, hyperuricaemia; ECG: LVH and/or ventricular ectopics (extrasystoles). May exacerbate or activate SLE in susceptible patients.
Volume depletion & electrolyte imbalance, dry mouth, thirst, lethargy, drowsiness, muscle pain & cramps, hypotension, hypersensitivity reactions e.g. rashes, photosensitivity, thrombocytopenia, jaundice, pancreatitis; fatigue, weakness; may precipitate an attack of gout; impotence, hyperglycaemia; anorexia, gastric irritation, nausea, vomiting, constipation, diarrhoea, sialadenitis, dizziness, raised Ca concentration. Hypersensitivity reactions.
HCTZ has not been studied well in pregnant women, but it is known to pass through the placenta to a developing fetus. The risks to the fetus are uncertain.Use is not recommended and a decision should be made to discontinue breastfeeding or discontinue the drug, taking into account the importance of the drug to the mother.
The most common signs and symptoms observed are those caused by electrolyte depletion (hypokalaemia, hypochloraemia, hyponatraemia) and dehydration resulting from excessive diuresis. If digitalis has also been administered, hypokalaemia 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 methods. If required, give oxygen or artificial respiration for respiratory impairment.
Keep below 30°C temperature, away from light & moisture. Keep out of the reach of children.
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