Diuretics

Diuretics are used in the treatment of hypertension, chronic renal failure, and the reduction of the extracellular fluid (ECF) volume in oedematous states. They act on particular segments of the renal tubule to decrease the reabsorption of sodium from the luminal fluid. Each inhibits a specific transporter in renal tubular cells.


Problems

Diuretics are usually well tolerated. However:

Diuretics are usually given once daily, and the timing can be adjusted for social convenience. Intravenous administration is reserved for emergency treatment or diuretic resistance (see below). Thiazides are usually adequate in the treatment of mild oedema and hypertension. If hypokalaemia is a recurrent problem, a combination with a potassium-sparing diuretic may be better tolerated than continuous potassium supplementation

Effectiveness Drug Major actions
Medium THIAZIDES (Benzothiadiazines)
including Metolazone, Indapamide, Chlortalidone
Inhibit reabsorption of NaCl in early distal tubule.
Inhibit reabsorption of NaCl in proximal tubule.
Inhibit some reabsorption of NaHCO3 in proximal and distal tubules.
High LOOP DIURETICS
Furosemide (Frusemide)
Bumetanide
Torasemide
Inhibit reabsorption of NaCl in thick ascending limb of Loop of Henle.
Increase renal perfusion.
K+-sparing Spironolactone Aldosterone antagonist – inhibits Na+/K+ exchange in collecting tubule.
Triamterene
Amiloride
Inhibit reabsorption of Na+ in collecting tubule.

Acetazolamide is a weakly effective diuretic that inhibits some reabsorption of NaHCO3 in proximal and distal tubules. It is not clinically useful as a diuretic but can be used to reduce aqueous humour production (glaucoma) and to prevent mountain sickness (unlicensed indication).
Thiazide-like drugs include chlortalidone (longer action), indapamide, and metolazone.


Diuretic resistance

In states of avid sodium retention (e.g. nephrotic syndrome or severe cardiac failure) and in some patients with renal failure, usual oral doses of loop diuretics may be ineffective.


Further info

  • Hypovolaemia is a predictable effect of over-treatment
  • Hyponatraemia, hypokalaemia, metabolic alkalosis may occur.
  • Hyperglycaemia, modest hyperlipidaemia, hyperuricaemia and gout may occur
  • Potassium-sparing diuretics may cause hyperkalaemia, especially in renal failure, or in combination with ACE inhibitors
  • Hypersensitivity reactions, impotence, and other effects may be attributed to diuretics, but often these have other causes
  • Cramps may be a symptom of over-diuresis.
    • Check and restrict patient’s intake of sodium and fluid.
    • Daily weight – useful for self-monitoring at home as well as in hospital
    • Using loop diuretics, double the dose every day or two until the maximum is reached.
    • Intravenous loop diuretic may be more effective.
    • Next consider adding an oral thiazide diuretic to produce ‘sequential blockade’, potentiating the effectiveness of the loop diuretic. There is a significant danger of over-diuresis with this combination: weigh daily, then reduce thiazide to alternate days or longer intervals until it can be stopped. Monitor electrolyes and renal function regularly.
    • Add potassium-sparing diuretic.
    • Monitoring of 24h urinary sodium and careful input/output charts are valuable if there is still difficulty. If high urinary sodium but no weight loss, sodium intake must still be too high.