| Diuretics | |
|---|---|
| Drug class | |
 Furosemide 125 mg vials forintravenous application | |
| Class identifiers | |
| Use | Forced diuresis,hypertension |
| ATC code | C03 |
| External links | |
| MeSH | D004232 |
| Legal status | |
| In Wikidata | |
Adiuretic (/ˌdaɪjʊˈrɛtɪk/) is any substance that promotesdiuresis, the increased production ofurine. This includesforced diuresis. A diuretic tablet is sometimes colloquially called awater tablet. There are several categories of diuretics. All diuretics increase the excretion ofwater from the body, through thekidneys. There exist several classes of diuretic, and each works in a distinct way. Alternatively, anantidiuretic, such asvasopressin (antidiuretic hormone), is an agent or drug which reduces the excretion of water in urine.
Inmedicine, diuretics are used to treatheart failure,liver cirrhosis,hypertension,influenza,water poisoning, and certainkidney diseases. Some diuretics, such asacetazolamide, help to make theurine morealkaline, and are helpful in increasingexcretion of substances such asaspirin in cases ofoverdose or poisoning. Diuretics are sometimes abused by people with aneating disorder, especially people withbulimia nervosa, with the goal of losing weight.[citation needed]
Theantihypertensive actions of some diuretics (thiazides andloop diuretics in particular) are independent of their diuretic effect.[1][2] That is, the reduction in blood pressure is not due to decreased blood volume resulting from increasedurine production, but occurs through other mechanisms and at lower doses than that required to producediuresis.Indapamide was specifically designed with this in mind, and has a largertherapeutic window forhypertension (without pronounced diuresis) than most other diuretics.[citation needed]
High-ceiling diuretics may cause a substantial diuresis – up to 20%[3] of the filtered load ofNaCl (salt) and water. This is large in comparison to normalrenal 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 asfurosemide, inhibit the body's ability to reabsorbsodium at the ascending loop in thenephron, 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 includeethacrynic acid andtorasemide.[citation needed]
Thiazide-type diuretics such ashydrochlorothiazide act on the distal convoluted tubule and inhibit thesodium-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 unknownvasodilator effect that decreases blood pressure by decreasing resistance.[4]
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 includeacetazolamide andmethazolamide.[citation needed]
These are diuretics which do not promote the secretion ofpotassium into the urine; thus, potassium is retained and not lost as much as with other diuretics.[citation needed] 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:
The term "calcium-sparing diuretic" is sometimes used to identify agents that result in a relatively low rate of excretion ofcalcium.[5]
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 inhypocalcemia, or unwanted inhypercalcemia.[citation needed]
Thethiazides and potassium-sparing diuretics are considered to be calcium-sparing diuretics.[6]
By contrast, loop diuretics promote a significant increase in calcium excretion.[8] This can increase risk of reduced bone density.[9]
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 thekidney, particularly the peritubular capillaries. This reduces medullary osmolality and thus impairs the concentration of urine in theloop 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.[10]
It was previously believed that the primary mechanism of osmotic diuretics such asmannitol is that they are filtered in theglomerulus, 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.[citation needed]
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 asdiabetes 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 somedrugs, especiallystimulants, may also increase blood glucose and thus increase urination.[citation needed].
The term "low-ceiling diuretic" is used to indicate a diuretic has a rapidly flatteningdose effect curve (in contrast to "high-ceiling", where the relationship is close to linear). Certain classes of diuretic are in this category, such as thethiazides.[11]
Diuretics are tools of considerable therapeutic importance. First, they effectively reduceblood 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.[12]
| Classification of common diuretics and their mechanisms of action. | |||
|---|---|---|---|
| Class | Examples | Mechanism | Location (numbered in distance along nephron) |
| Ethanol | drinking alcohol | Inhibitsvasopressin secretion | |
| Water | Inhibitsvasopressin secretion | ||
| Acidifyingsalts | calcium chloride,ammonium chloride | 1. | |
| Arginine vasopressin receptor 2 antagonists | amphotericin B,lithium[13][14] | Inhibits vasopressin's action | 5.collecting duct |
| Selective vasopressin V2 antagonist (sometimes called aquaretics) | tolvaptan,[15]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 (aquaresis), an increase in serum sodium concentration, a decrease in urine osmolality, and an increase in urine output.[16] | 5.collecting duct |
| Na-H exchanger antagonists | dopamine[17] | Promotes Na+ excretion | 2.proximal tubule[17] |
| Carbonic anhydrase inhibitors | acetazolamide,[17]dorzolamide | Inhibits H+ secretion, resultant promotion of Na+ and K+ excretion | 2.proximal tubule |
| Loop diuretics | bumetanide,[17]ethacrynic acid,[17]furosemide,[17]torsemide | Inhibits theNa-K-2Cl symporter | 3. medullarythick ascending limb |
| Osmotic diuretics | glucose (especially in uncontrolled diabetes),mannitol | Promotes osmotic diuresis | 2.proximal tubule,descending limb |
| Potassium-sparing diuretics | amiloride,spironolactone,eplerenone,triamterene,potassium canrenoate. | Inhibition ofNa+/K+ exchanger: Spironolactone inhibitsaldosterone action, Amiloride inhibitsepithelial sodium channels[17] | 5.cortical collecting ducts |
| Thiazides | bendroflumethiazide,hydrochlorothiazide | Inhibits reabsorption byNa+/Cl− symporter | 4.distal convoluted tubules |
| Xanthines | caffeine,theophylline,theobromine | Inhibits reabsorption of Na+, increaseglomerular filtration rate | 1. tubules |
Caffeine when initially consumed in large quantities is both a diuretic and anatriuretic,[18] but this effect disappears with chronic consumption.[19][20][21]
The main adverse effects of diuretics arehypovolemia,hypokalemia,hyperkalemia,hyponatremia,metabolic alkalosis,metabolic acidosis, andhyperuricemia.[17]
| Adverse effect | Diuretics | Symptoms |
|---|---|---|
| hypovolemia | ||
| hypokalemia | ||
| hyperkalemia | ||
| hyponatremia | ||
| metabolic alkalosis | ||
| metabolic acidosis | ||
| hypercalcemia | ||
| hyperuricemia |
A common application of diuretics is for the purposes of invalidatingdrug tests.[22] Diuretics increase the urine volume and dilutedoping agents and their metabolites. Another use is to rapidly lose weight to meet aweight category in sports likeboxing andwrestling.[23][24]
