Diuretic
A diuretic is any substance that promotes diuresis, the increased production of urine. This includes 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. Alternatively, an antidiuretic, such as vasopressin, is an agent or drug which reduces the excretion of water in urine.
Medical uses
In medicine, diuretics are used to treat heart failure, liver cirrhosis, hypertension, influenza, water poisoning, 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 sometimes abused by people with an eating disorder, especially people with bulimia nervosa, with the goal of losing weight.The antihypertensive actions of some diuretics 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 than most other diuretics.
Types
High ceiling/loop diuretic
High ceiling diuretics may cause a substantial diuresis – up to 20% of the filtered load of NaCl and water. This is large in comparison to normal renal sodium reabsorption which leaves only about 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 nephron, which leads to an excretion of water in the urine, whereas water normally follows sodium back into the extracellular fluid. Other examples of high ceiling loop diuretics include ethacrynic acid and torasemide.Thiazides
-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 increased loss of water that has not been retained from the body as a result of a concomitant relationship with sodium loss from the convoluted tubule.The short-term anti-hypertensive action is based on the fact that thiazides decrease preload, decreasing blood pressure. On the other hand, the long-term effect is due to an unknown vasodilator effect that decreases blood pressure by decreasing resistance.
Carbonic anhydrase inhibitors
s inhibit the enzyme carbonic anhydrase which is found in the proximal convoluted tubule. This results in several effects including bicarbonate accumulation in the urine and decreased sodium absorption. Drugs in this class include acetazolamide and methazolamide.Potassium-sparing diuretics
These are diuretics which do not promote the secretion of potassium into the urine; thus, potassium is retained and not lost as much as with 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. Similar agents are eplerenone
and potassium canreonate. - Epithelial sodium channel blockers: amiloride and triamterene.
Calcium-sparing diuretics
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.
Osmotic diuretics
s are substances that increase osmolarity but have limited tubular epithelial cell permeability. They work primarily by expanding extracellular fluid and plasma volume, therefore increasing blood flow to the kidney, particularly the peritubular capillaries. This reduces medullary osmolality and thus impairs the concentration of urine in the loop of Henle. Furthermore, the limited tubular epithelial cell permeability increases osmolality and thus water retention in the filtrate.It was previously believed that the primary mechanism of osmotic diuretics such as mannitol is that they are filtered in the glomerulus, but cannot be reabsorbed. Thus their presence leads to an increase in the osmolarity of the filtrate and 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 reabsorption capacity of the kidney. When this happens, glucose remains in the filtrate, leading to the osmotic retention of water in the urine. Glucosuria causes a loss of hypotonic water and Na+, leading to a hypertonic state with signs of volume depletion, such as dry mucosa, hypotension, tachycardia, and decreased turgor of the skin. 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 a diuretic has a rapidly flattening dose effect curve. Certain classes of diuretic are in this category, such as the thiazides.Mechanism of action
Diuretics are tools of considerable therapeutic importance. First, they effectively reduce blood pressure. Loop and thiazide diuretics are secreted from the proximal tubule via the organic anion transporter-1 and exert their diuretic action by binding to the Na-K-2Cl co-transporter type 2 in the thick ascending limb and the Na-Cl co-transporter in the distal convoluted tubule, respectively.Classification of common diuretics and their mechanisms of action.
| Examples | Mechanism | Location | |
| – | ethanol, water | Inhibits vasopressin secretion | |
| Acidifying salts | calcium chloride, ammonium chloride | 1. | |
| Arginine vasopressin receptor 2 antagonists | amphotericin B, lithium | Inhibits vasopressin's action | 5. collecting duct |
| Selective vasopressin V2 antagonist | tolvaptan, conivaptan | Competitive vasopressin antagonism leads to decreased number of aquaporin channels in the apical membrane of the renal collecting ducts in kidneys, causing decreased water reabsorption. This causes an increase in renal free water excretion, an increase in serum sodium concentration, a decrease in urine osmolality, and an increase in urine output. | 5. collecting duct |
| Na-H exchanger antagonists | dopamine | Promotes Na+ excretion | 2. proximal tubule |
| Carbonic anhydrase inhibitors | acetazolamide, dorzolamide | Inhibits H+ secretion, resultant promotion of Na+ and K+ excretion | 2. proximal tubule |
| Loop diuretics | bumetanide, ethacrynic acid, furosemide, torsemide | Inhibits the Na-K-2Cl symporter | 3. medullary thick ascending limb |
| Osmotic diuretics | glucose, mannitol | Promotes osmotic diuresis | 2. proximal tubule, descending limb |
| Potassium-sparing diuretics | amiloride, spironolactone, eplerenone, triamterene, potassium canrenoate. | Inhibition of Na+/K+ exchanger: Spironolactone inhibits aldosterone action, Amiloride inhibits epithelial sodium channels | 5. cortical collecting ducts |
| Thiazides | bendroflumethiazide, hydrochlorothiazide | Inhibits reabsorption by Na+/Cl− symporter | 4. distal convoluted tubules |
| Xanthines | caffeine, theophylline, theobromine | Inhibits 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.
As a diuretic is any substance that promotes the production of urine, aquaretics that cause the excretion of free water are a sub-class. This includes all the hypotonic aqueous preparations, including pure water, black and green teas, and teas prepared from herbal medications. Any given herbal medication will include a vast range of plant-derived compounds, some of which will be active drugs that may also have independent diuretic action.
Adverse effects
The main adverse effects of diuretics are hypovolemia, hypokalemia, hyperkalemia, hyponatremia, metabolic alkalosis, metabolic acidosis, and hyperuricemia.| Adverse effect | Diuretics | Symptoms |
| hypovolemia |
| |
| hypokalemia | ||
| hyperkalemia | ||
| hyponatremia | ||
| metabolic alkalosis | ||
| metabolic acidosis | ||
| hypercalcemia | ||
| hyperuricemia |