A diuretic () is any substance that promotes

diuresis Diuresis () is the excretion of urine, especially when excessive (polyuria). The term collectively denotes the physiologic processes underpinning increased urine production by the kidneys during maintenance of fluid balance. In healthy people, ...

, the increased production of

urine Urine is a liquid by-product of metabolism in humans and many other animals. In placental mammals, urine flows from the Kidney (vertebrates), kidneys through the ureters to the urinary bladder and exits the urethra through the penile meatus (mal ...

. This includes

forced diuresis Diuresis () is the excretion of urine, especially when excessive (polyuria). The term collectively denotes the physiologic processes underpinning increased urine production by the kidneys during maintenance of fluid balance. In healthy people, ...

. A diuretic tablet is sometimes colloquially called a water tablet. There are several categories of diuretics. All diuretics increase the excretion of

water Water is an inorganic compound with the chemical formula . It is a transparent, tasteless, odorless, and Color of water, nearly colorless chemical substance. It is the main constituent of Earth's hydrosphere and the fluids of all known liv ...

from the body, through the

kidneys In humans, the kidneys are two reddish-brown bean-shaped blood-filtering organs that are a multilobar, multipapillary form of mammalian kidneys, usually without signs of external lobulation. They are located on the left and right in the retro ...

. There exist several classes of diuretic, and each works in a distinct way. Alternatively, an

antidiuretic An antidiuretic is a chemical substance, substance that helps to control fluid balance in an animal's body by reducing urination, opposing diuresis. Its effects are opposite that of a diuretic. The major endogeny (biology), endogenous antidiuretics ...

, such as

vasopressin Mammalian vasopressin, also called antidiuretic hormone (ADH), arginine vasopressin (AVP) or argipressin, is a hormone synthesized from the ''AVP'' gene as a peptide prohormone in neurons in the hypothalamus, and is converted to AVP. It ...

(

antidiuretic hormone Mammalian vasopressin, also called antidiuretic hormone (ADH), arginine vasopressin (AVP) or argipressin, is a hormone synthesized from the ''AVP'' gene as a peptide prohormone in neurons in the hypothalamus, and is converted to AVP. It ...

), is an agent or drug which reduces the excretion of water in urine.

Medical uses

medicine Medicine is the science and Praxis (process), practice of caring for patients, managing the Medical diagnosis, diagnosis, prognosis, Preventive medicine, prevention, therapy, treatment, Palliative care, palliation of their injury or disease, ...

, diuretics are used to treat

heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome caused by an impairment in the heart's ability to Cardiac cycle, fill with and pump blood. Although symptoms vary based on which side of the heart is affected, HF ...

liver cirrhosis Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, chronic liver failure or chronic hepatic failure and end-stage liver disease, is a chronic condition of the liver in which the normal functioning tissue, or parenchyma, is replaced ...

hypertension Hypertension, also known as high blood pressure, is a Chronic condition, long-term Disease, medical condition in which the blood pressure in the artery, arteries is persistently elevated. High blood pressure usually does not cause symptoms i ...

influenza Influenza, commonly known as the flu, is an infectious disease caused by influenza viruses. Symptoms range from mild to severe and often include fever, runny nose, sore throat, muscle pain, headache, coughing, and fatigue. These sympto ...

, water poisoning, and certain

kidney disease Kidney disease, or renal disease, technically referred to as nephropathy, is damage to or disease of a kidney. Nephritis is an Inflammation, inflammatory kidney disease and has several types according to the location of the inflammation. Infla ...

s. Some diuretics, such as

acetazolamide Acetazolamide, sold under the trade name Diamox among others, is a medication used to treat glaucoma, epilepsy, acute mountain sickness, periodic paralysis, idiopathic intracranial hypertension (raised brain pressure of unclear cause), heart f ...

, help to make the

alkaline In chemistry, an alkali (; from the Arabic word , ) is a basic salt of an alkali metal or an alkaline earth metal. An alkali can also be defined as a base that dissolves in water. A solution of a soluble base has a pH greater than 7.0. The ...

, and are helpful in increasing

excretion Excretion is elimination of metabolic waste, which is an essential process in all organisms. In vertebrates, this is primarily carried out by the lungs, Kidney (vertebrates), kidneys, and skin. This is in contrast with secretion, where the substa ...

of substances such as

aspirin Aspirin () is the genericized trademark for acetylsalicylic acid (ASA), a nonsteroidal anti-inflammatory drug (NSAID) used to reduce pain, fever, and inflammation, and as an antithrombotic. Specific inflammatory conditions that aspirin is ...

in cases of

overdose A drug overdose (overdose or OD) is the ingestion or application of a drug or other substance in quantities much greater than are recommended. Retrieved on September 20, 2014.

or poisoning. Diuretics are sometimes abused by people with an

eating disorder An eating disorder is a mental disorder defined by abnormal eating behaviors that adversely affect a person's health, physical or mental health, mental health. These behaviors may include eating too much food or too little food. Types of eatin ...

, especially people with

bulimia nervosa Bulimia nervosa, also known simply as bulimia, is an eating disorder characterized by binge eating (eating large quantities of food in a short period of time, often feeling out of control) followed by compensatory behaviors, such as self-indu ...

, with the goal of losing weight. The

antihypertensive Antihypertensives are a class of drugs that are used to treat hypertension (high blood pressure). Antihypertensive therapy seeks to prevent the complications of high blood pressure, such as stroke, heart failure, kidney failure and myocardial infa ...

actions of some diuretics (

thiazide Thiazide () refers to both a class of sulfur-containing organic molecules and a class of diuretics based on the chemical structure of benzothiadiazine. The thiazide drug class was discovered and developed at Merck and Co. in the 1950s. The firs ...

s and

loop diuretic Loop diuretics are pharmacological agents that primarily inhibit the Na-K-Cl cotransporter located on the luminal membrane of cells along the thick ascending limb of the loop of Henle. They are often used for the treatment of hypertension and e ...

s 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

Indapamide Indapamide is a thiazide-like diuretic drug used in the treatment of hypertension, as well as decompensated heart failure. Combination preparations with perindopril (an ACE inhibitor antihypertensive) are available. The thiazide-like diuretics ...

was specifically designed with this in mind, and has a larger therapeutic window for

(without pronounced diuresis) than most other diuretics.

Types

High-ceiling/loop diuretics

High-ceiling diuretics may cause a substantial diuresis – up to 20% of the filtered load of

NaCl Sodium chloride , commonly known as edible salt, is an ionic compound with the chemical formula NaCl, representing a 1:1 ratio of sodium and chloride ions. It is transparent or translucent, brittle, hygroscopic, and occurs as the mineral hali ...

(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 Furosemide, sold under the brand name Lasix among others, is a loop diuretic medication used to treat edema due to heart failure, liver scarring, or kidney disease. Furosemide may also be used for the treatment of high blood pressure. It can ...

, inhibit the body's ability to reabsorb

sodium Sodium is a chemical element; it has Symbol (chemistry), symbol Na (from Neo-Latin ) and atomic number 11. It is a soft, silvery-white, highly reactive metal. Sodium is an alkali metal, being in group 1 element, group 1 of the peri ...

at the ascending loop in the

nephron The nephron is the minute or microscopic structural and functional unit of the kidney. It is composed of a renal corpuscle and a renal tubule. The renal corpuscle consists of a tuft of capillaries called a glomerulus and a cup-shaped structu ...

, 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 Torasemide, also known as torsemide, is a diuretic medication used to treat hypervolemia, fluid overload due to heart failure, kidney disease, and liver disease. It is a less preferred treatment for high blood pressure. It is taken by mouth or ...

Thiazides

Thiazide Thiazide () refers to both a class of sulfur-containing organic molecules and a class of diuretics based on the chemical structure of benzothiadiazine. The thiazide drug class was discovered and developed at Merck and Co. in the 1950s. The firs ...

-type diuretics such as

hydrochlorothiazide Hydrochlorothiazide, sold under the brand name Hydrodiuril among others, is a diuretic medication used to treat hypertension and swelling due to fluid build-up. Other uses include treating diabetes insipidus and renal tubular acidosis and t ...

act on the distal convoluted tubule and inhibit the

sodium-chloride symporter The sodium-chloride symporter (also known as Na+-Cl− cotransporter, NCC or NCCT, or as the thiazide-sensitive Na+-Cl− cotransporter or TSC) is a cotransporter in the kidney which has the function of reabsorbing sodium and chloride ions from ...

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 Vasodilation, also known as vasorelaxation, is the widening of blood vessels. It results from relaxation of smooth muscle cells within the vessel walls, in particular in the large veins, large arteries, and smaller arterioles. Blood vessel wal ...

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

and methazolamide.

Potassium-sparing diuretics

These are diuretics which do not promote the secretion of

potassium Potassium is a chemical element; it has Symbol (chemistry), symbol K (from Neo-Latin ) and atomic number19. It is a silvery white metal that is soft enough to easily cut with a knife. Potassium metal reacts rapidly with atmospheric oxygen to ...

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 Spironolactone, sold under the brand name Aldactone among others, is classed as a diuretic medication. It can be used to treat edema, fluid build-up due to hepatic cirrhosis, liver disease or kidney disease. It is also used to reduce risk o ...

, which is a

competitive antagonist A receptor antagonist is a type of receptor ligand or drug that blocks or dampens a biological response by binding to and blocking a receptor rather than activating it like an agonist. Antagonist drugs interfere in the natural operation of recep ...

aldosterone Aldosterone is the main mineralocorticoid steroid hormone produced by the zona glomerulosa of the adrenal cortex in the adrenal gland. It is essential for sodium conservation in the kidney, salivary glands, sweat glands, and colon. It plays ...

Aldosterone Aldosterone is the main mineralocorticoid steroid hormone produced by the zona glomerulosa of the adrenal cortex in the adrenal gland. It is essential for sodium conservation in the kidney, salivary glands, sweat glands, and colon. It plays ...

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 Calcium is a chemical element; it has symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar to it ...

. 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 Hypocalcemia is a medical condition characterized by low calcium levels in the blood serum. The normal range of blood calcium is typically between 2.1–2.6 mmol/L (8.8–10.7 mg/dL, 4.3–5.2 mEq/L), while levels less than 2.1 ...

, or unwanted in

hypercalcemia Hypercalcemia, also spelled hypercalcaemia, is a high calcium (Ca2+) level in the blood serum. The normal range for total calcium is 2.1–2.6 mmol/L (8.8–10.7 mg/dL, 4.3–5.2 mEq/L), with levels greater than 2.6 mmol/L def ...

. The

s 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. This can increase risk of reduced bone density.

Osmotic diuretics

Osmotic diuretics (e. g.,

mannitol Mannitol is a type of sugar alcohol used as a sweetener and medication. It is used as a low calorie sweetener as it is poorly absorbed by the intestines. As a medication, it is used to decrease pressure in the eyes, as in glaucoma, and to l ...

) 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 In humans, the kidneys are two reddish-brown bean-shaped blood-filtering organ (anatomy), organs that are a multilobar, multipapillary form of mammalian kidneys, usually without signs of external lobulation. They are located on the left and rig ...

, particularly the peritubular capillaries. This reduces medullary osmolality and thus impairs the concentration of urine in the

loop of Henle In the kidney, the loop of Henle () (or Henle's loop, Henle loop, nephron loop or its Latin counterpart ''ansa nephroni'') is the portion of a nephron that leads from the proximal convoluted tubule to the distal convoluted tubule. Named after it ...

(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. It was previously believed that the primary mechanism of osmotic diuretics such as

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 Glucose is a sugar with the Chemical formula#Molecular formula, molecular formula , which is often abbreviated as Glc. It is overall the most abundant monosaccharide, a subcategory of carbohydrates. It is mainly made by plants and most algae d ...

, 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 Diabetes mellitus, commonly known as diabetes, is a group of common endocrine diseases characterized by sustained hyperglycemia, high blood sugar levels. Diabetes is due to either the pancreas not producing enough of the hormone insulin, or th ...

, the concentration of glucose in the blood (

hyperglycemia Hyperglycemia is a condition where unusually high amount of glucose is present in blood. It is defined as blood glucose level exceeding 6.9 mmol/L (125 mg/dL) after fasting for 8 hours or 10 mmol/L (180 mg/dL) 2 hours after eating. Blood gluc ...

) 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 Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal ...

, and decreased turgor of the skin. Use of some

drug A drug is any chemical substance other than a nutrient or an essential dietary ingredient, which, when administered to a living organism, produces a biological effect. Consumption of drugs can be via insufflation (medicine), inhalation, drug i ...

s, especially

stimulant Stimulants (also known as central nervous system stimulants, or psychostimulants, or colloquially as uppers) are a class of drugs that increase alertness. They are used for various purposes, such as enhancing attention, motivation, cognition, ...

s, 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 Blood pressure (BP) is the pressure of Circulatory system, circulating blood against the walls of blood vessels. Most of this pressure results from the heart pumping blood through the circulatory system. When used without qualification, the term ...

. 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. Caffeine when initially consumed in large quantities is both a diuretic and a natriuretic, but this effect disappears with chronic consumption.

Adverse effects

The main adverse effects of diuretics are

hypovolemia Hypovolemia, also known as volume depletion or volume contraction, is a state of abnormally low extracellular fluid in the body. This may be due to either a loss of both salt and water or a decrease in blood volume. Hypovolemia refers to the loss ...

hypokalemia Hypokalemia is a low level of potassium (K+) in the blood serum. Mild low potassium does not typically cause symptoms. Symptoms may include feeling tired, leg cramps, weakness, and constipation. Low potassium also increases the risk of an a ...

hyperkalemia Hyperkalemia is an elevated level of potassium (K+) in the blood. Normal potassium levels are between 3.5 and 5.0 mmol/L (3.5 and 5.0 mEq/L) with levels above 5.5mmol/L defined as hyperkalemia. Typically hyperkalemia does not cause symptoms. Oc ...

hyponatremia Hyponatremia or hyponatraemia is a low concentration of sodium in the Serum (blood), blood. It is generally defined as a sodium concentration of less than 135 mmol/L (135 mEq/L), with severe hyponatremia being below 120 mEq/L. Symp ...

metabolic alkalosis Metabolic alkalosis is an acid-base disorder in which the pH of tissue is elevated beyond the normal range (7.35–7.45). This is the result of decreased hydrogen ion concentration, leading to increased bicarbonate (), or alternatively a dire ...

metabolic acidosis Metabolic acidosis is a serious electrolyte disorder characterized by an imbalance in the body's acid-base balance. Metabolic acidosis has three main root causes: increased acid production, loss of bicarbonate, and a reduced ability of the kidn ...

, and

hyperuricemia Hyperuricaemia or hyperuricemia is an abnormally high level of uric acid in the blood. In the pH conditions of body fluid, uric acid exists largely as urate, the ion form. Serum uric acid concentrations greater than 6 mg/dL for females, 7 ...

Abuse in sports

A common application of diuretics is for the purposes of invalidating

drug test A drug test (also often toxicology screen or tox screen) is a technical analysis of a biological specimen, for example urine, hair, blood, breath, sweat, or saliva, oral fluid/saliva—to determine the presence or absence of specified parent ...

s. Diuretics increase the urine volume and dilute doping agents and their metabolites. Another use is to rapidly lose weight to meet a weight category in sports like

boxing Boxing is a combat sport and martial art. Taking place in a boxing ring, it involves two people – usually wearing protective equipment, such as boxing glove, protective gloves, hand wraps, and mouthguards – throwing Punch (combat), punch ...

and

wrestling Wrestling is a martial art, combat sport, and form of entertainment that involves grappling with an opponent and striving to obtain a position of advantage through different throws or techniques, within a given ruleset. Wrestling involves di ...

References

External links

Diagram at cvpharmacology.com

"Caffeine and Electrolyte Imbalance"
by Dana George August 23, 2011 {{Authority control