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)