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Diuretic drugs

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Carol McLoughlin

Diuretics are drugs used to increase the amount of urine produced by the kidneys and increase the excretion of sodium and other electrolytes (Karch, 2003).

They are most commonly used in patients with cardiac conditions, to treat the oedema and congestion associated with heart failure, and in renal disease and liver cirrhosis. They affect the filtration and concentration of the circulating blood volume. As the intravascular fluid reduces and becomes more concentrated, the oncotic pull increases, drawing fluid from the interstitial spaces back into the circulation, reducing oedema.

Diuretics and modes of action

All diuretics produce a similar effect, although their modes of action may differ (see diagram, opposite page).

Diuretics are indicated for treating:

  • Oedema
  • Congestive heart failure
  • Hypertension
  • Renal disease
  • Liver disease
  • Glaucoma
  • Raised intracranial pressure.

There are five classes of diuretics: thiazides and thiazide-like diuretics; loop diuretics; carbonic anhydrase inhibitors; potassium-sparing diuretics; and osmotic diuretics.

Thiazide: Thiazide diuretics, such as bendroflumethiazide and chlortalidone, inhibit the reabsorption of sodium and chloride in the distal tubule of the nephron. They work by blocking the chloride pump, inhibiting the active pumping of chloride out of the tubule and the associated passive movement of sodium back into the circulation.

They are used to treat oedema associated with congestive heart failure (CHF) or with liver and renal failure. They are also used as adjuncts for treating hypertension (Karch, 2003).

Loop diuretics:
Loop diuretics, such as frusemide, bumetanide and ethacrynic acid, are the most potent diuretics that act on the loop of Henle segment of the renal nephrons (Downie et al, 2003). They are used in pulmonary oedema due to left ventricular heart failure, producing rapid relief of breathlessness when given intravenously. They are also effective in relieving oedema and oliguria in renal failure. Loop diuretics block the chloride pump, affecting the reabsorption of chloride and sodium.

Carbonic anhydrase inhibitors:
These are relatively mild diuretics, used mainly in the treatment of glaucoma (Karch, 2003). Carbonic anhydrase inhibitors decrease the production of aqueous humor in the eye, which reduces intraoccular pressure. These drugs slow down the movement of hydrogen ions, leading to the excretion of more sodium and bicarbonate in the urine. Inhibiting the reabsorption of sodium coincides with less water reabsorption and hence the diuretic effect.

Potassium-sparing diuretics:
Potassium-sparing diuretics such as amiloride and spironolactone act on the distal tube segment of the nephron. They are not as potent as loop diuretics but are useful in those at risk of hypokalaemia (patients on digoxin or taking anti-arrhythmiac drugs). Potassium-sparing diuretics are often used as adjuncts to thiazides or loop diuretics. When given with thiazides, they counteract the increased glucose and uric acid levels associated with thiazide diuretic therapy (Woodrow, 2003).

Osmotic diuretics:
Osmotic diuretics such as mannitol and urea are used to reduce intracranial or intraoccular pressure. Mannitol may also be used to promote excretion of toxins in cases of drug poisoning (Woodrow, 2003).

Osmotic diuretics pass through the glomerulus, increasing the osmotic pressure of the filtrate, thus reducing the amount of water normally reabsorbed by the tubules and loop of Henle, so increasing urinary output. As they have little effect on sodium reabsorption their use in heart failure associated with sodium retention is limited, and they may also have an adverse effect on blood volume.


Diuretics may be given orally or by slow intravenous injection or IV infusion.

Thiazides are absorbed from the gastrointestinal tract with an onset of action of between one and three hours. They are metabolised in the liver and excreted in urine (Karch, 2003).

Loop diuretics are metabolised and excreted primarily through urine. The onset of diuresis is rapid (within minutes with IV administration) and may extend for over six hours (Hopkins, 1999).

Potassium-sparing diuretics are well absorbed, protein bound and widely distributed. They are metabolised in the liver and excreted in the urine. Carbonic anhydrase inhibitors are rapidly absorbed and widely distributed and are excreted in the urine. The osmotic diuretics are freely filtered in the renal glomerulus, poorly reabsorbed and resistant to metabolism.


Diuretics act by inhibiting tubular reabsorption and so increase the elimination of water and electrolytes (Hopkins, 1999).

The thousands of nephrons in the kidneys act as filters, allowing some fluid and electrolytes to be reabsorbed into the circulating blood volume and channelling other fluid and waste products to the bladder for excretion as urine. Nephrons are made up of a Bowman’s capsule containing a mesh of blood vessels - the glomerulus - and two tubules connected by the loop of Henle.

In healthy kidneys, blood cells, plasma proteins and lipids are unable to pass through the glomerulus and the filtrate consists of electrolytes and the water-soluble constituents of plasma. As the filtrate passes through the tubules its concentration changes with the movement of water and electrolytes back into the circulation.

Most reabsorption occurs in the proximal tubule where water, 70% of sodium, all the potassium and varying amounts of other solutes are taken up (Hopkins, 1999). Further reabsorption of sodium occurs in the loop of Henle and lastly in the distal tubule, where sodium is exchanged for potassium. When the filtrate reaches the urine-collecting duct, further water may be added or removed according to antidiuretic harmone secretion.

Diuretics act at different points along the nephron tubules, influencing the carrier systems that transfer ions into and out of the nephrons. The loop diuretics prevent the transport of sodium chloride out of the distal tubule into the interstitial tissues (Hopkins, 1999).

Thiazide diuretics act at the beginning of the distal convoluted tubule, decreasing the active reabsorption of sodium and chloride. Blocking the chloride pump retains the chloride and sodium in the tubule, which is excreted in urine.

The potassium-sparing diuretics act by excreting sodium in exchange for potassium. Spironolactone is an aldosterone antagonist that inhibits the action of aldosterone in reabsorbing sodium and excreting potassium.

Osmotic diuretics do not affect sodium reabsorption but rather reabsorption of water by increasing the osmotic pressure of the filtrate, drawing in and retaining water in the tubules.

Cautions and contraindications

Diuretics are contraindicated in patients with known drug hypersensitivity and those with electrolyte imbalance. They should be used cautiously in anyone with renal dysfunction, as changes in blood flow and kidney perfusion may further compromise a diseased kidney. Diuretics have glucose-elevating effects, and may not be suitable in cases of diabetes mellitus.

Diuretics compete with uric acid for secretion in the proximal tubule, so a build-up uric acid may occur leading to hyperuricaemia and gout (Downie, 2003). Caution is advised in patients with liver disease, which may interfere with drug metabolism and lead to toxicity. The elderly may be more susceptible to the side-effects, and lower doses are advised initially.

Some diuretics (thiazides and loop diuretics) are known to cross the placenta and others have been associated with fetal abnormalities: they are not recommended in pregnancy unless benefits to the mother outweigh the potential effects on the fetus (Karch, 2003).


Interactions may occur with:

  • Non-steroidal anti-inflammatory agents: risk of renal failure
  • Corticosteroids: increase potassium loss
  • Lithium: can cause lithium intoxication
  • Hypotensive agents, which potentiate blood pressure decrease
  • Digitalis: with increased potential for digitalis toxicity
  • Probenecid (Benemid) to block uric acid retention
  • Antidiabetic agents: loss of diabetic control
  • Aminoglycosides potentiating the nephrotoxic and ototoxic effects
  • Anticonvulsants: phenytoin reduces diuretic effect of frusemide

Source: Karch, 2003; Woodrow, 2002


  • Hypokalaemia, which may lead to cardiac arrhythmias
  • Hyperkalaemia is possible with potassium-sparing diuretics
  • Hypochloraemia may lead to alkalosis
  • Metabolic acidosis owing to excessive bicarbonate loss
  • Hyponatraemia and dehydration, with hypokalaemia
  • Gastrointestinal reactions (such as anorexia, nausea and diarrhoea)
  • Postural hypertension, vertigo, headache
  • Fatigue, weakness, lethargy
  • Hyperglycaemia; increased uric acid
  • Tinnitus, hearing impairment and blurred vision

Source: Woodrow, 2002


  • Diuretics are drugs that increase the excretion of sodium and therefore water from the kidneys
  • They are used to relieve oedema associated with congestive heart failure, liver and renal failure, and as adjuncts to antihypertension medication
  • Classes of diuretics differ in their site of action in the renal nephrons and in intensity of effect
  • Caution is required in conditions exacerbated by changes in fluid and electrolyte balance
  • Adverse effects include electrolyte imbalance, hypotension, hypovolaemia, hypoglycaemia and metabolic alkalosis
  • Patients receiving diuretics need to be monitored for fluid loss and retention, and electrolyte imbalance

Find out about fluid balance in our urea and electrolytes section

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