A diuretic () is any substance that promotes diuresis, the increased production of urine. This includes forced diuresis. A diuretic tablet is sometimes colloquially called a water tablet. There are several categories of diuretics. All diuretics increase the excretion of water from the body, through the kidneys. There exist several classes of diuretic, and each works in a distinct way. Alternatively, an antidiuretic, such as vasopressin (antidiuretic hormone), 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
. 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
drug overdose or poisoning. Diuretics are sometimes abused by athletes who seek to excrete water for quick weight loss and/or to mask their use of banned substances,
and by people with
, especially people with
bulimia nervosa, who seek to lose weight.
The antihypertensive actions of some diuretics ( and in particular) are independent of their diuretic effect.
Types
High-ceiling/loop diuretics
High-ceiling diuretics may cause a substantial diuresis – up to 20%
of the filtered load of
sodium chloride (salt) 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
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 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
Carbonic anhydrase inhibitors 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 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 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 in calcium excretion.
Osmotic diuretics
(e. g.,
mannitol) 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 (which usually uses the high osmotic and solute gradient to transport solutes and water). Further, the limited tubular epithelial cell permeability increases osmolality and thus water retention in the filtrate.
[Du, Xiaoping. Diuretics . Department of Pharmacology, University of Illinois at Chicago.]
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 (hyperglycemia) 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 , especially , 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 (in contrast to "high-ceiling", where the relationship is close to linear). Certain classes of diuretic are in this category, such as the
.
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.
|
|
| Ethanol | drinking alcohol | Inhibits vasopressin secretion | |
| 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 (sometimes called aquaretics) | tolvaptan, | 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 (aquaresis), 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 |
| bumetanide,[ ethacrynic acid,][ furosemide,][ torsemide] | Inhibits the Na-K-2Cl symporter | 3. medullary thick ascending limb |
| glucose (especially in uncontrolled diabetes), 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 |
| bendroflumethiazide, hydrochlorothiazide | Inhibits reabsorption by Na+/Cl− symporter | 4. distal convoluted tubules |
| caffeine, theophylline, theobromine | Inhibits reabsorption of Na+, increase glomerular filtration rate | 1. tubules |
Caffeine when initially consumed in large quantities is both a diuretic and a Natriuresis,
Adverse effects
The main adverse effects of diuretics are
hypovolemia,
hypokalemia,
hyperkalemia,
hyponatremia, metabolic alkalosis, metabolic acidosis, and
hyperuricemia.
[
]
Abuse in sports
A common application of diuretics is for the purposes of invalidating .
See also
External links
