Thiazide diuretics

Mechanism of action

Thiazide diuretics work by inhibiting sodium absorption at the beginning of the distal convoluted tubule (DCT) via blocking the Na⁺-Cl⁻ symporter.

The increased sodium load in the distal nephron and collecting ducts results in compenstory increases in Na⁺-K⁺-ATPase and Na⁺-Ca²⁺ antiporter activity. This results in increased potassium loss and increased calcium reabsorption respectively hence thaizide diuretics may lead to hypokalaemia and hypercalceamia.

Indications

Thiazide diuretics are now primarily used in the treatment of oedema.

In the past thiazide diuretics were often first choice drugs for the management of hypertension and heart failure. Loop diuretics are better for reducing overload and now preferred by NICE for management of heart failure. Thiazide-like diuretics such as indapamide and chlortalidone have replaced the thiazide diuretics in the NICE hypertension guidelines.

Common side effects:

• dehydration
• postural hypotension
• hyponatraemia, hypokalaemia, hypercalcaemia
• gout
• impaired glucose tolerance
• impotence

Rare side effects:

• thrombocytopaenia
• agranulocytosis
• photosensitivity rash
• pancreatitis