Diuretics

Diuretics

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 does so in a distinct way.

Types

1. 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 when compared to normal renal sodium reabsorption which 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.

2. Thiazides

   Thiazide-type diuretics such as hydrochlorothiazide act on the distal convoluted tubule and inhibit the Sodium-chloride symporter leading to a retention of water in the urine as water normally follows penetrating solutes. Frequent urination is due to the increase loss of water that has not being retained from the body as a result of concomitant relationship with sodium loss from the convoluted tubule.

3. 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. The term "potassium-sparing" refers to an effect rather than a mechanism or location; nonetheless, the term almost always refers to two specific classes that have their effect at similar locations:

   • Aldosterone antagonists: 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. A similar agent is potassium canreonate.
   • Epithelial sodium channel blockers: amiloride and triamterene.

4. Calcium-sparing diuretics

   The term "calcium-sparing diuretic" is sometimes used to identify agents that result in a relatively low rate of excretion of calcium.

   The reduced concentration of calcium in the urine can lead to an increased rate of calcium in serum. The sparing effect on calcium can be beneficial in hypocalcemia, or unwanted in hypercalcemia.

   The thiazides and potassium-sparing diuretics are considered to be calcium-sparing diuretics.

   • The thiazides cause a net decrease in calcium lost in urine.
   • The potassium-sparing diuretics cause a net increase in calcium lost in urine, but the increase is much smaller than the increase associated with other diuretic classes.

   By contrast, loop diuretics promote a significant increase calcium excretion. This can increase risk of reduced bone density.

5. 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.

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