Hydrochlorothiazide

Indications

Oral
Hypertension
Adult: Initially, 12.5 mg daily. Usual dose: 25-50 mg daily, either alone or combined with other antihypertensives, up to 100 mg daily, if necessary.

CrCl (ml/min)	Dosage Recommendation
<10	Avoid.

Oral
Oedema associated with heart failure
Adult: Usual dosage: 25-100 mg daily in the morning, may reduce to 25-50 mg daily or intermittently. Up to 200 mg daily may be used as initial doses in severe cases.

CrCl (ml/min)	Dosage Recommendation
<10	Avoid.

Oral
Nephrogenic diabetes insipidus
Adult: Initial dose: Up to 100 mg daily.
Child: Initially, 1-2 mg/kg/day in 1-2 divided doses; <6 mth: up to 3 mg/kg/day.

CrCl (ml/min)	Dosage Recommendation
<10	Avoid.

Contraindications

Severe hepatic and renal impairment, Addison's disease, preexisting hypercalcaemia, anuria, sulphonamide allergy. Pregnancy, lactation.

Warnings / Precautions

Existing electrolyte disturbances, hepatic cirrhosis, severe heart failure, oedema, elderly, renal impairment. Monitor for signs of fluid and electrolyte disturbance. Hepatic impairment, DM, gout, hyperlipidaemia, hypercalcaemia, hyperuricaemia; ECG: LVH and/or ventricular ectopics (extrasystoles). May exacerbate or activate SLE in susceptible patients.

Adverse Reactions

Volume depletion and electrolyte imbalance, dry mouth, thirst, lethargy, drowsiness, muscle pain and 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.
Potentially Fatal: Hypersensitivity reactions.

Overdose Reactions

Lethargy, nausea, weakness and electrolyte imbalance, possibly progress to coma within a few hr with minimal depression of respiratory and CV function and with no evidence of dehydration or serum electrolyte changes. GI irritation and hypermotility, temporary elevation of the BUN, serum electrolyte changes (e.g., hypokalemia, hypochloremia, hyponatremia) may occur in renally impaired patients. Empty stomach by inducing vomiting with ipecac syrup If patient is conscious. Cathartics should not be admin as they may promote loss of fluid and electrolytes. Supportive and symptomatic treatment with monitoring of serum electrolytes, renal, respiratory, and CV function. Replace fluid and electrolytes where necessary.

Drug Interactions

May cause hyponatraemia when used with carbamazepine. May increase risk of toxicity when used with allopurinol or tetracyclines. Potentiates hypotensive effect of α-blockers and ACE inhibitors. Diuretic-induced hypokalaemia may increase the toxicity of digitalis glycosides and risk of arrhythmias when used with drugs that prolong QT interval. May increase serum concentrations of lithium when used together. Concurrent use with alcohol, barbiturates and opioids may enhance diuretic-enhanced orthostatic hypotension. Antihypertensive effect may be reduced by corticosteroids, NSAIDs or carbenoxolone. May enhance the nephrotoxicity of NSAIDs.
Potentially Fatal: Enhances neuromuscular blocking action of competitive muscle relaxants. Impaired control of diabetes by oral hypoglycaemic agents.
See Below for More hydrochlorothiazide Drug Interactions

Mechanism of Actions

Hydrochlorothiazide inhibits the reabsorption of Na and chloride at the beginning of the distal convoluted tubule. It causes natriuretic effect mainly by decreasing Na and chloride reabsorption in the cortical segment of the ascending limb of the loop of Henle by inhibition of a specific Na⁺Cl^- co-transporter.
Onset: 2 hr (oral).
Duration: 6-12 hr (oral).
Absorption: Fairly absorbed from the GI tract; peak plasma concentrations after 4 hr (oral).
Distribution: Crosses the placenta; enters the breast milk; bound to RBCs.
Excretion: Urine (as unchanged drug); 5-15 hr (elimination half-life).