Thiazide and thiazide-like diuretics e.g. bendroflumethiazide, chlorthalidone, metolazone

These act on the DCT and collecting ducts and inhibit the sodium/chloride co-transporter. These 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).

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.
  • 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 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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