Thiazide Diuretics

Mechanism of Action

  • Acts on the Na-Cl cotransporters in the proximal part of the distal tubule to increase sodium (and thus water) excretion from the blood
  • NB The major haemodynamic effect is actually a reduction in peripheral resistance due to alterations in the contractile responses of vascular smooth muscle

Indications

  • Mild-moderate hypertension, particularly in patients >55 years old and the Afro-Caribbean population
    • Bendroflumethiazide was most commonly used; however, the NICE guidelines currently recommend newer thiazide-like diuretics for hypertension e.g. Chlortalidone or Indapamide
      • Bendroflumethiazide is still preferred in patients with heart failure with oedema
  • Oedema

Cautions/Contraindications

  • May exacerbate diabetes, gout, SLE
  • Monitor U&Es in patients on higher doses, long-term use, or with renal impairment
    • Use with caution in nephrotic syndrome, hyperaldosteronism and malnourishment
    • Avoid in refractory hypokalaemia, hyponatraemia and hypercalcaemia, symptomatic hyperuricaemia (gout) and Addison’s disease
  • Caution with liver disease and avoid in severe hepatic failure
  • A potassium sparing diuretic may be helpful in patients with hypokalaemia to avoid consequences e.g. coma.
  • Avoid in renal disease where eGFR < 30ml/min/1.73² (ineffective)
  • Avoid during pregnancy

Side effects

  • U&E/metabolic disturbances
    • Hypokalaemia (consider also primary hyperaldosteronism if fall >0.3mmol/l if serum sodium is in high-normal range)
    • Hyperuricaemia – risk of gout
    • Hyperglycaemia and risk of diabetes/worsening diabetes
    • Hypercalcaemia
    • Hypomagnesaemia
    • Hypochloraemic alkalosis
  • Other side effects include mild GI upset, postural hypotension
    • Rarely, blood problems e.g. agranulocytosis, leucopenia, thrombocytopenia; Impotence.

Interactions

  • May increase cardiac toxicity of cardiac glycosides e.g. digoxin, or with anti-arrhythmic drugs e.g. flecainide, sotalol
  • May also reduce excretion of certain drugs e.g. lithium
  • Can increase the risk of hypokalaemia when taken with many other drugs

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