The term diuretic refers to a drug which acts upon the kidneys to produce an increased output of sodium salt and water in the urine. These drugs are used to treat disorders of the heart, kidneys or liver which result in an excessive retention of fluids in the body, so much so that swelling may be visible – this is called oedema, or what used to be called dropsy. Swelling of the tissues is usually more obvious in the feet and ankles because of the effect of gravity. In a patient confined to bed the fluid gravitates to the lower part of the back which may then be swollen. Excessive fluid inside the abdominal cavity is called ascites. Diuretics are also used to treat disorders in which fluid accumulates in the lung tissue (pulmonary oedema) – this may be a serious medical emergency.
Some weak diuretics are used to decrease the fluid pressure inside the eyeball, as in the treatment of glaucoma, where the drainage of the eye fluid is impaired. In addition, diuretics are used to counter the salt and water retention produced by other drugs, and to treat overdose with certain drugs that are excreted by the kidneys, by increasing output of urine. However, their most common use is in the treatment of raised blood pressure.
The kidneys exercise a most delicate and complex control over the body’s salt and water balance. Salt at first enters the urine but is subsequently reabsorbed into the blood-stream according to body needs. The amount of salt in the urine governs the amount of water passed out by the process known as osmosis (water moves from the weaker solution to the stronger when separated by a partially permeable membrane). The process of osmosis takes the direction from the weaker to the stronger solution so that if there is a lot of salt in the urine, a lot of water will pass out and be excreted in the urine. In addition, there are other rather complex chemical and hormonal processes which affect the amount of salt and water passed out in the urine.
The great majority of diuretics in use today act directly upon the kidneys by depressing the reabsorption of salt from the urine back into the blood-stream, thus producing an increased output of salt and water from the body (diuresis) – the increase in water excretion is therefore a secondary result of decreased salt reabsorption. Some diuretics as well as affecting the reabsorption of sodium also interfere with the reabsorption of potassium. This produces a low blood potassium level which may produce muscle weakness, constipation and loss of appetite; more seriously, a low blood potassium affects the heart. It also sensitizes the heart to digoxin and related drugs which are frequently used to treat heart failure and disorders of heart rhythm.
There are three main groups of diuretics – thiazides and related drugs, loop diuretics and potassium sparing diuretics. Other diuretics include mild diuretics used to treat glaucoma, osmotic diuretics and xanthine diuretics.
Thiazide Diuretics and Related Drugs
Thiazides comprise the largest group of diuretic drugs. They act on the tubules in the kidneys (proximal segment of the distal convoluted tubule), preventing salt reabsorption. These drugs are of moderate potency and vary in their duration of effect. When used in effective diuretic dosage they all increase the excretion of potassium. They are used to treat disorders where fluid is retained in the body, as in heart failure. They are also used in low doses alone or in combination with other drugs to treat raised blood pressure (see p.000).
bendroflumethiazide(bendrofluazide) (Aprinox, Berkozide, Neo-Bendromax, Neo-Naclex)
benzthiazide (in Dytide)
clopamide (in Viskaldix)
indapamide (Natrilix, Nindaxa, Opumide, Natramid)
All thiazide diuretics produce similar effects and adverse effects, but vary in their rate of absorption from the gut, in their potency and in their duration of action. They reduce sodium, potassium and magnesium blood levels and sometimes increase blood calcium. They may send up the blood sugar and cause sugar to appear in the urine in diabetics and other susceptible individuals. They may also cause an increase in blood uric acid level and trigger an attack of gout in some people and they may cause a rise in blood fat levels. They should be used with caution in patients with impaired kidney or liver function or with diabetes and in the elderly. They may rarely cause nausea, dizziness, weakness, numbness and pins and needles, skin rashes, allergic reactions, impotence, blood disorders and sensitivity of the skin to sunlight. Note: These adverse effects seldom occur with the low doses used to treat raised blood pressure.
These include bumetanide (Burinex), furosemide(frusemide) (Froop, Frusol, Lasix, Rusyde) and torasemide (Torem). They inhibit salt reabsorption in the ascending limb of the loop of Henle in the kidneys and are therefore known as loop diuretics.
These are more potent than the thiazide diuretics and although they are chemically different they have similar effects. They act quickly when given by injection and the duration of their effect is short. Dosage must be controlled with caution since high doses may produce a massive output of urine leading to a fall in blood pressure, which in turn may result in a decreased production of urine by the kidneys. They may cause a fall in blood potassium, sodium, magnesium and calcium and a rise in blood glucose and uric acid. They are used to treat fluid retention due to heart, kidney or liver failure. Furosemide(frusemide) and torasemide are used in small dosages to treat raised blood pressure.
Aldosterone is a hormone produced by the adrenal glands. It plays a role in the body’s salt and water balancing mechanisms. An excess of it may be produced by a tumour of the adrenal glands or in response to certain disorders such as severe congestive heart failure or cirrhosis of the liver associated with the collection of increased fluid in the abdomen (ascites). It works on the kidneys, where it increases the reabsorption of sodium and the excretion of potassium. There are drugs which block these effects, thus increasing the excretion of sodium (which takes water with it) and reducing the excretion of potassium.
Spironolactone (Aldactone, Spirospare) is an aldosterone antagonist used to treat oedema caused by cirrhosis of the liver, nephrotic syndrome, and chronic congestive heart failure.
Other Potassium-sparing Diuretics
Triamterene (Dytac) increases sodium excretion in the urine but reduces potassium loss. It is not a very potent diuretic and it is usually combined with a thiazide diuretic.
Amiloride (Amilamont, Amilospare) has effects and uses similar to triamterene.
The principal use of triamterene and amiloride is in combination with a thiazide diuretic in order to reduce potassium loss in the urine. Occasionally the use of such combinations, particularly in patients with impaired kidney function, can cause dangerously high blood potassium levels. Therefore, blood potassium levels should be regularly monitored in these patients.
Warnings: The doses of thiazide or loop diuretics used to treat heart failure may cause potassium loss and patients may need to take supplementary potassium daily; however, this can generally be avoided by using potassium-sparing diuretics or by combining a potassium-sparing diuretic with a thiazide or a loop diuretic.
The small doses of thiazide or loop diuretics used to treat raised blood pressure seldom require supplementary potassium.
Supplementary potassium ought to be considered in elderly patients who may take a diet low in potassium; in those patients taking digoxin or a related drug or an anti-arrhythmic drug, in whom a fall in blood potassium level could be harmful; in patients suffering from chronic diarrhoea or laxative abuse in whom potassium loss may occur in the faeces; and in patients with overproduction of aldosterone (hyperaldosteroidism) due to serious heart, liver or kidney disease.
Including potassium in diuretic tablets has never been convincingly shown to be of any benefit in preventing a fall in body potassium levels. A potassium supplement is best taken on its own. Potassium chloride is the best salt to use because of the loss of chloride which diuretics produce. Effervescent potassium chloride tablets (Kloref, Sando-K) are satisfactory. Slow-release potassium chloride (Slow-K) tablets may, rarely, cause ulcers of the intestine. Liquid preparations of potassium chloride are safest (e.g. Kay-Cee-L syrup). Small doses should be used in patients with impaired kidney function and elderly patients because of the risk of a rise in blood potassium levels.
Diuretics Combined with Potassium Salt
Burinex K – bumetanide plus potassium
Diumide-K Continus – furosemide(frusemide) plus potassium
Lasikal – furosemide(frusemide) plus potassium
Lasix + K – furosemide(frusemide) plus potassium
Neo-Naclex-K – bendroflumethiazide(bendrofluazide) plus potassium
Combined Diuretic Preparations
Potassium-sparing Diuretics with Other Diuretics
Amiloride with a thiazide diuretic
Amil-Co – amiloride and hydrochlorothiazide
Amilmaxco 5/50 – amiloride and hydrochlorothiazide
co-amilozide – amiloride and hydrochlorothiazide
Moduret 25, Moduretic, Zida-Co – amiloride and hydrochlorothiazide
Moduretic – amiloride and hydrochlorothiazide
Navispare – amiloride and cyclopenthiazide
Triamterene with a thiazide diuretic
co-triamterzide – triamterene and hydrochlorothiazide
Dyazide – triamterene and hydrochlorothiazide
Dytide – triamterene and benzthiazide
Kalspare – triamterene and chlorthalidone
Triamax-Co, Triam-Co – triamterene and hydrochlorothiazide
Amiloride with a loop diuretic
Aridil – amiloride and furosemide(frusemide)
Burinex A – amiloride and bumetanide
co-amilofruse – amiloride and furosemide(frusemide)
Fru-Co – amiloride and furosemide(frusemide)
Froop-Co, Frumil – amiloride and furosemide(frusemide)
Lasoride – amiloride and furosemide(frusemide)
Triamterene with a loop diuretic
Frusene – triamterene and furosemide(frusemide)
Spironolactone with a thiazide diuretic
Aldactide 25 – spironolactone and hydroflumethiazide
Aldactide 50 – spironolactone and hydroflumethiazide
Spironolactone with a loop diuretic
Lasilactone – spironolactone and furosemide(frusemide)
Mild Diuretics Used to Treat Glaucoma
In the early 1950s a group of diuretics was introduced which blocked the action of an enzyme (an organic catalyst) which is involved in the kidneys’ control of water and salt balance. The enzyme is responsible for exchanging hydrogen ions for sodium ions in the urine so that body sodium is conserved. The diuretics block this action and cause the sodium not to be reabsorbed. This group of drugs includes acetazolamide (Diamox).
In the treatment of glaucoma they reduce the formation of fluid inside the eye and reduce the pressure (see p. 53).
Any substance which passes out of the blood in the kidneys and into the urine may interfere with salt reabsorption, resulting in an increase in urine volume and the excretion of larger amounts of sodium and potassium. The ones used for this purpose are called osmotic diuretics and they should produce no other action in the body. They include mannitol, urea, glucose and sucrose.
Mannitol is a type of alcohol which is excreted by the kidneys and because it is not reabsorbed it causes diuresis. It has to be given by intravenous injection. Glucose and sucrose are sugars and act in a similar way.
Osmotic diuretics may be used to keep urine flow going after severe injury, in order to prevent kidney damage, to eliminate certain drugs after overdose (e.g. aspirin, barbiturates) and to reduce the pressure due to fluid accumulation inside the eyes in glaucoma and inside the skull after head injury.
This group includes caffeine, theophylline and theobromine. They are present in tea, coffee, cola and cocoa. They are mild diuretics and work both directly and indirectly on the kidneys to produce a diuresis.