Bendroflumathiazide

Question 1

Drug class?

Answer 1

Thiazide diuretics

Question 2

How does it work?

Answer 2

Act on the early segements of the distal tubule, where they inhibit NaCl reabsorption by binding to the synporter responsible for the electroneutral cotransport of Na+Cl-. Excretion of Cl-, Na+ and accompanying H2O increased. Increased Na+ load in distal tubule stimulates Na+ exchange with K+ and H+ increasing their excretion and causing hypokalaemia and a metabolic alkalosis.

Question 3

Indications?

Answer 3

• Heart failure

- Hypertension

Question 4

Contra-indications?

Answer 4

Refractory hypokalaemia, hyponatraemia, hypocalcaemia, symptomatic hyperuricaemia, Addison’s disease.

Question 5

Side-effects?

Answer 5

1. Hypokalaemia – increased Na+ load stimulates Na+ exchange with K+ and H+, increasing their excretion.
2. Hyperuricaemia – Uric acid levels in blood often increased because thiazides/loop diuretics are secreted by the organic acid secretory system in the tubules and compete for uric acid secretion. May precipitate gout.
3. Hyperglycaemia – Glucose tolerance may be impaired and thiazides are contraindicated in people with type II diabetes.
4. Lipids – Thizaides increase plasma cholesterol levels at least during first 6 months of administration.

Question 6

Possible interactions?

Answer 6

• Sensitivity to digitalis glycosides may be increased by the hypokalaemic effect of concurrent bendroflumethiazide.
• Serum lithium concentrations may be increased by concurrent use of thiazide diuretics.
• Non-steroidal anti-inflammatory agents may blunt the diuretic and antihypertensive effects of thiazide diuretics. Diuretics may increase the risk of nephrotoxicity of NSAIDs.
• Xanthines, beta-agonists, ACTH, corticosteroids, acetazolamide and carbenoxolone may exacerbate the hypokalaemia associated with thiazide use. Thiazide diuretics may enhance the neuromuscular blocking effects of the non-depolarising muscle relaxants, e.g. tubocurarine.
• Thiazides may enhance the effects of antihypertensive agents, while postural hypotension associated with therapy may be enhanced by concomitant ingestion of alcohol, barbiturates or opioids.
• Oestrogens and combined oral contraceptives may antagonise the diuretic effect of thiazides.

Question 7

Elimination?

Answer 7

Eliminated rapidly renally – about 6-12 hour duration.