A diuretic () is any substance that promotes
diuresis, 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. 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. 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
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,
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, help to make the
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 ...
more
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 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 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
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 ...
(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 (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
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-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
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, which is a
competitive antagonist of
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, 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 in calcium excretion.
This can increase risk of reduced bone density.
Osmotic diuretics
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
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 (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
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
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) 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
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
thiazides.
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,
hyperkalemia,
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 acidosis, and
hyperuricemia.
[
]
Abuse in sports
A common application of diuretics is for the purposes of invalidating drug tests. 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 ...
.
See also
* Antidiuretic
* Laxative
* Diuresis
* Hydration
* Water poisoning
* Dehydration
References
External links
Diagram at cvpharmacology.com
"Caffeine and Electrolyte Imbalance"
by Dana George August 23, 2011
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