Diuretic
Diuretics | |
---|---|
Forced diuresis, hypertension | |
ATC code | C03 |
External links | |
MeSH | D004232 |
Legal status | |
In Wikidata |
A diuretic (
Medical uses
In
The
Types
High-ceiling/loop diuretics
High-ceiling diuretics may cause a substantial diuresis – up to 20%
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
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.[citation needed]
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.[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:
- potassium canreonate.[citation needed]
- Epithelial sodium channel blockers: amiloride and triamterene.[citation needed]
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.[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 in
The thiazides and potassium-sparing diuretics are considered to be calcium-sparing diuretics.[6]
- The thiazides cause a net decrease in calcium lost in urine.[7]
- 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.[7]
By contrast, loop diuretics promote a significant increase in calcium excretion.[8] This can increase risk of reduced bone density.[9]
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, 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.[10]
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.[citation needed]
Low-ceiling diuretics
The term "low-ceiling diuretic" is used to indicate a diuretic has a rapidly flattening
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.[12]
Classification of common diuretics and their mechanisms of action. | |||
---|---|---|---|
Class | Examples | Mechanism | Location (numbered in distance along nephron) |
Ethanol | drinking alcohol
|
Inhibits vasopressin secretion | |
Water | Inhibits vasopressin secretion | ||
Acidifying salts | calcium chloride, ammonium chloride | 1. | |
Arginine vasopressin antagonists
receptor 2 |
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 | torsemide
|
Inhibits the Na-K-2Cl symporter
|
3. medullary thick 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 of Na+/K+ exchanger: Spironolactone inhibits aldosterone action, Amiloride inhibits epithelial sodium channels[17]
|
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 |
Caffeine when initially consumed in large quantities is both a diuretic and a natriuretic,[18] but this effect disappears with chronic consumption.[19][20][21]
Adverse effects
The main adverse effects of diuretics are hypovolemia, hypokalemia, hyperkalemia, hyponatremia, metabolic alkalosis, metabolic acidosis, and hyperuricemia.[17]
Adverse effect | Diuretics | Symptoms |
---|---|---|
hypovolemia | ||
hypokalemia |
| |
hyperkalemia | ||
hyponatremia | ||
metabolic alkalosis |
| |
metabolic acidosis | ||
hypercalcemia
|
| |
hyperuricemia |
Abuse in sports
A common application of diuretics is for the purposes of invalidating
See also
- Antidiuretic
- Laxative
- Diuresis
- Hydration
- Water poisoning
- Dehydration
References
- PMID 637001.
- S2CID 8531997.
- ^ "TheDrugMonitor.com is available at DomainMarket.com". TheDrugMonitor.com is available at DomainMarket.com. Archived from the original on January 17, 2008.
- PMID 20528637.
- S2CID 21202583.
- PMID 15165661.
- ^ ISBN 978-0-7817-4118-7.
- S2CID 36030615.
- S2CID 41216704.
- ^ Du, Xiaoping. Diuretics Archived April 7, 2006, at the Wayback Machine. Department of Pharmacology, University of Illinois at Chicago.
- ISBN 978-0-8493-7774-7.
- S2CID 43171023.
- ISBN 978-0-08-092046-7.
- ISBN 978-94-009-0449-1.
- PMID 17105757.
- PMC 2799145.
- ^ ISBN 978-1-4160-2328-9.
- S2CID 41617469. Archived from the original(PDF) on 8 March 2019.
- ^ O'Connor A (4 March 2008). "Really? The claim: caffeine causes dehydration". New York Times. Retrieved 3 August 2009.
- S2CID 46352603.
- S2CID 378245.
- ^ Bahrke, Michael (2002). Performance-Enhancing Substances in Sport and Exercise.
- ^ Agence France Presse (2012-07-17). "UCI announces adverse analytical finding for Frank Schleck". VeloNews. Retrieved 2012-07-18.
- PMID 20718736.
External links
- Diagram at cvpharmacology.com
- "Caffeine and Electrolyte Imbalance" by Dana George August 23, 2011