Introduction

Thiazide and thiazide-like diuretics are commonly used for management of hypertension, as well as management of oedema (e.g. in heart failure or liver failure). They are moderately potent diuretics as opposed to very potent diuretics (loop diuretics) and mildly potent diuretics (potassium sparing diuretics).

Their antihypertensive effect is mainly due to vasodilation and not diuresis, and this effect is achieved at low doses, whereas the diuretic effect is dose dependent and mainly occurs at higher doses.

Examples

Thiazide diuretics and thiazide-like diuretics e.g. hydrochlorothiazide (HCT), bendroflumethiazide, indapamide. Chlorthalidone and metolazone are the thiazide-like diuretics. 

Mechanism

Thiazide diuretics act on the DCT and collecting ducts and inhibit the sodium/chloride co-transporter. They are less effective than loop diuretics (they prevent reabsoprtion of about 6-8% of the sodium).
They are slow to act, but have a longer duration of action than loop diuretics.
These drugs are not as effective in patients with renal failure. They are pretty useless once the GFR is below 20ml/min.
Over time, the drugs will produce vasodilation, which causes a useful hypotensive effect.
The drugs are not filtered by the kidney, but arrive via the anion transport mechanism (same as for loop diuretics).
Mechanism of action of thiazide diuretics

Mechanism of action of thiazide diuretics. Image by Haisook at English Wikipedia

Unwanted effects

  • Hypokalaemia
  • Salt and water depletion
  • Decreased excretion of calcium – this is the opposite of loop diuretics and the mechanism is not understood. It is unlikely that hypercalcemia will result.
  • Increased glucose intolerance – this gradually builds up over several weeks, so that the level of blood glucose rises. This is due to the hypokalaemia – the reduced levels of potassium reduce insulin release due to their involvement in the release mechanism. The reduced insulin means tissues cannot take up glucose as readily, and as a result, glucose levels gradually rise. The effect is usually reversed if treatment is stopped.
  • Hyperlipidaemia. The effect is small but could possibly constitute an increased risk of cardiovascular disease.
  • Impotence – reported by 10% of middle-aged men
  • Nocturia and polyuria – caused by the diuresis.

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