Diuretics

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File:Renal Diuretics.gif

This illustration shows where some types of diuretics act, and what they do.

A diuretic is any drug that elevates the rate of urination and thus provides a means of forced diuresis. There are several categories of diuretics. All diuretics increase the excretion of water from bodies, although each class of diuretic does so in a distinct way.

Types

High ceiling loop diuretics

High ceiling diuretics are diuretics that may cause a substantial diuresis - up to 20% of the filtered load of NaCl and water. This is huge, compared to that normal renal sodium reabsorption leaves only ~0.4% of filtered sodium in the urine.

Loop diuretics have this ability, and are therefore often synonymous with high ceiling diuretics. Loop diuretics, such as furosemide, inhibit the body's ability to reabsorb sodium at the ascending loop in the kidney which leads to a retention of water in the urine as water normally follows sodium back into the extracellular fluid (ECF). Other examples of high ceiling loop diuretics include ethacrynic acid, torsemide and bumetanide.

Thiazides

Drugs such as hydrochlorothiazide act on the distal tubule and inhibit the Sodium-chloride symporter leading to a retention of water in the urine as water normally follows penetrating solutes.

Potassium-sparing diuretics

These are diuretics which do not promote the secretion of potassium into the urine; thus, potassium is spared and not lost as much as in other diuretics. Such drugs include spironolactone which is a competitive antagonist of aldosterone. Aldosterone normally adds sodium channels in the principal cells of the collecting duct and late distal tubule of the nephron. Spironolactone prevents aldosterone from entering the principal cells, preventing sodium reabsorption. Other examples of potassium-sparing diuretics are amiloride, triamterene and potassium canreonate.

Osmotic diuretics

Compounds such as mannitol are filtered in the glomerulus, but cannot be reabsorbed. Their presence leads to an increase in the osmolarity of the filtrate. To maintain osmotic balance, water is retained in the urine.

Glucose, like mannitol, is a sugar that can behave as an osmotic diuretic. Unlike mannitol, glucose is commonly found in the blood. However, in certain conditions such as diabetes mellitus, the concentration of glucose in the blood exceeds the maximum resorption capacity of the kidney. When this happens, glucose remains in the filtrate, leading to the osmotic retention of water in the urine. Use of some drugs, especially stimulants may also increase blood glucose and thus increase urination.

Low ceiling diuretics

The term "low ceiling diuretic" is used to indicate that a diuretic has a rapidly flattening dose effect curve (in contrast to "high ceiling", where the relationship is close to linear. It refers to a pharmacological profile, not a chemical structure. However, there are certain classes of diuretic which usually fall into this category, such as the thiazides.

Uses

In medicine, diuretics are used to treat heart failure, liver cirrhosis, hypertension and certain kidney diseases. Some diuretics, such as acetazolamide, help to make the urine more alkaline and are helpful in increasing excretion of substances such as aspirin in cases of overdose or poisoning. Diuretics are often abused by sufferers of eating disorders, especially bulimics, in attempts at weight loss.

The antihypertensive actions of some diuretics (thiazides and loop diuretics in particular) are independent of their diuretic effect. That is, the reduction in blood pressure is not due to decreased blood volume resulting from increased urine production, but occurs through other mechanisms and at lower doses than that required to produce diuresis. Indapamide was specifically designed with this in mind, and has a larger therapeutic window for hypertension (without pronounced diuresis) than most other diuretics.

Mechanism of action

Classification of common diuretics and their mechanisms of action:

	Examples	Mechanism	Location (numbered in distance along nephron)
-	Ethanol, Water	inhibits vasopressin secretion	1.
Acidifying salts	CaCl2, NH4Cl		1.
Arginine vasopressin receptor 2 antagonists	amphotericin B, lithium citrate	inhibit vasopressin's action	5. collecting duct
Aquaretics	Goldenrod, Juniper	Increases blood flow in kidneys	1.
Na-H exchanger antagonists	dopamine	promote Na+ excretion	2. proximal tubule
Carbonic anhydrase inhibitors	acetazolamide, dorzolamide	inhibit H+ secretion, resultant promotion of Na+ and K+ excretion	2: proximal tubule
Loop diuretics	bumetanide, ethacrynic acid, furosemide, torsemide	inhibit the Na-K-2Cl symporter	3. medullary thick ascending limb
Osmotic diuretics	glucose (especially in uncontrolled diabetes), mannitol	promote osmotic diuresis	2. proximal tubule, descending limb
Potassium-sparing diuretics	amiloride, spironolactone, triamterene, potassium canrenoate.	inhibition of Na+/K+ exchanger: Spironolactone inhibits aldosterone action, Amiloride inhibits epithelial sodium channels	5. cortical collecting ducts
Thiazides	bendroflumethiazide, hydrochlorothiazide	inhibit reabsorption by Na+/Cl- symporter	4. distal convoluted tubules
Xanthines	caffeine, theophylline	inhibit reabsorption of Na+, increase glomerular filtration rate	1. tubules

Chemically, diuretics are a diverse group of compounds that either stimulate or inhibit various hormones that naturally occur in the body to regulate urine production by the kidneys. Herbal medications are not inherently diuretics. They are more correctly called aquaretics.

Adverse effects

The main adverse effects of diuretics are hypovolemia, hypokalemia, hyperkalemia, hyponatremia, metabolic alkalosis, metabolic acidosis and hyperuricemia . Each are at risk of certain types of diuretics and present with different symptoms.

Adverse effect	Diuretics	Symptoms
Hypovolemia	loop diuretics thiazides	lassitude thirst muscle cramps hypotension
hypokalemia	acetazolamides loop diuretics thiazides	muscle weakness paralysis arrhythmia
Hyperkalemia	amilorides triamterenes spironolactone	arrhythmia muscle cramps paralysis
hyponatremia	thiazides furosemides	CNS symptoms coma
metabolic alkalosis	loop diuretics thiazides	arrhythmia CNS symptoms
metabolic acidosis	acetazolamides amilorides triamterene	Kussmaul respirations muscle weakness neurological symptoms lethargy coma seizures. stupor
hypercalcemia	thiazides	gout tissue calcification fatigue depression confusion anorexia nausea vomiting constipation pancreatitis increased urination
hyperuricemia	thiazides loop diuretics	gout

See also

• Antihyperensive drugs
• Caffeine
• Diuresis
• Probenecid
• Theophyline

External links

• Diagram at cvpharmacology.com

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