MECHANISM OF ACTION

  • InhibitNa+/Cl symporter in the distal convoluted tubules thereby reducing Na+ reabsorption and reducing water reabsorption.

INDICATIONS

  • Hypertension.
  • Oedema in heart failure.

CAUTIONS AND CONTRA-INDICATIONS

  • Electrolyte disturbances (including refractory hypokalaemia, hyponatraemia, hypercalcaemia and symptomatic hyperuricaemia).
  • Addison’s disease.
  • Avoid in breastfeeding mothers due to suppression of lactation.

SIDE-EFFECTS

  • Postural hypotension.
  • Hyponatraemia.
  • Hypokalaemia.
  • Hyperuricaemia (e.g. gout).
  • Hypercalcaemia.
  • Hyperglycaemia.
  • Male sexual dysfunction.
  • Suppression of lactation.
  • Raised LDL cholesterol

METABOLISM AND HALF-LIFE 

  • Metabolised in the liver.
  • t½ is 3–4h.

MONITORING 

  • Monitor plasma electrolytes for adverse effects as above.

DRUG INTERACTIONS

  • Enhanced hypotensive effect with other antihypertensives.
  • Increased risk of nephrotoxicity with NSAIDs.
  • Reduced hypoglycaemic effect of oral antidiabetic agents.

IMPORTANT POINTS 

  • Thiazides are less effective than loop diuretics because 90% of Na+ has been reabsorbed by the time the filtrate reaches the distal convoluted tubule.
  • Hypokalaemia results from increased activity of Naþ/Kþ ATPase in collecting ducts.
  • This is caused by increased Naþ in filtrate and an aldosterone-mediated effect (diuretic-induced hypovolaemia causes activation of the renin-angiotensin-aldosterone system)