Diuretic
Diuretics are "agents that promote the excretion of urine through their effects on kidney function."[1]
Physiology of sodium reabsorption in the kidney
| Location in nephron | Proportion of total sodium reabsorption accounted for |
Membrane transport protein Ion pump or ion channel |
Diuretics that act at this location |
|---|---|---|---|
| Proximal convulated tubule | 40% | Carbonic anhydrase Sodium-hydrogen antiporter (Ion pump) |
Carbonic anhydrase inhibitors |
| Late proximal tubule | Chloride-bicarbonate antiporter (Ion pump) | ||
| Loop of Henle: thin descending limb |
0% | Not applicable | Osmotic diuretics |
| Loop of Henle: thick ascending limb ('diluting segment') |
25% | Sodium potassium chloride symporter (Ion pump) | Loop diuretics |
| Distal convulated tubule | 10% | Sodium chloride symporter (Ion pump) | Thiazides |
| Collecting tubule | 2-5% | Mineralacorticoids receptors Sodium channel (Ion channel) |
Potassium-sparing diuretics |
Classification
Carbonic anhydrase inhibitors
Carbonic anhydrase inhibitors are a "class of compounds that reduces the secretion of h+ ions by the proximal kidney tubule through inhibition of carbonic anhydrases."[2][3]
Osmotic diuretic
Osmotic diuretics are "compounds that increase urine volume by increasing the amount of osmotically active solute in the urine. Osmotic diuretics also increase the osmolarity of plasma."[4]
Loop diuretics
More formally called sodium potassium chloride symporter inhibitors, these are agents that inhibit sodium-potassium-chloride symporters in the thick ascending limb at the junction of the Loop of Henle and distal kidney tubules.[5]
Thiazides
Thiazides are "heterocyclic compounds with sulfur and nitrogen in the ring. This term commonly refers to the benzothiadiazines that inhibit sodium-potassium-chloride symporters."[6] Examples include hydrochlorothiazide and chlorthalidone.
Potassium-sparing diuretics
These work in the collecting duct and late distal convoluted tubule either by inhibiting mineralacorticoids receptors or by blocking the epithelial sodium channel.[7][8] Amiloride is beter tolerated than triamterene. Their ability to treat hypertension is uncertain.[9]
Vasopressin antagonists
Tolvaptan, a vasopressin antagonist, may be beneficial according to a randomized controlled trial.[10][11] Tolvaptan is a selective cell surface receptors V2 antagonist in the distal nephron which causes loss of free water.[12] Other vasopressin antagonists act mainly on V1a cell surface receptors.
Brain (B-type) natriuretic peptide
Nesiritide, a brain (B-type) natriuretic peptide, may help patients with decompensated congestive heart failure according to a randomized controlled trial.[13] Natriuretic peptide causes diuresis, vasodilitation, and suppression of the renin-angiotensin system and sympathetic nervous system.[13]
Medical uses
Diuretics may be used to treat hypertension, heart failure, and other illnesses.[14] Occasionally high doses or combinations of diuretics are needed.[14][15][16][17]
Adverse effects
Many diuretics, aimed at sodium and water retention, may reduce potassium to dangerous levels. In addition to monitoring, it may be necessary, for example, to combine thiazide diuretics with supplemental potassium or potassium-sparing diuretics.
Hydrochlorothiazide at doses above 25 mg per day may be associated with sudden cardiac death.[18] This risk may be reduced by adding a potassium-sparing diuretic.[18]
References
- ↑ Anonymous (2024), Diuretic (English). Medical Subject Headings. U.S. National Library of Medicine.
- ↑ Anonymous (2024), Carbonic anhydrase inhibitors (English). Medical Subject Headings. U.S. National Library of Medicine.
- ↑ Katzung, Bertram G. (2001). “Diuretic Agents”, Basic & Clinical Pharmacology. New York: Lange Medical Books/McGraw-Hill, 249. ISBN 0-8385-0598-8.
- ↑ Anonymous (2024), Osmotic diuretics (English). Medical Subject Headings. U.S. National Library of Medicine.
- ↑ Anonymous (2024), Sodium Potassium Chloride Symporter Inhibitors (English). Medical Subject Headings. U.S. National Library of Medicine.
- ↑ Anonymous (2024), Thiazides (English). Medical Subject Headings. U.S. National Library of Medicine.
- ↑ Anonymous (2024), Sodium channel blockers (English). Medical Subject Headings. U.S. National Library of Medicine.
- ↑ Katzung, Bertram G. (2001). “Diuretic Agents”, Basic & Clinical Pharmacology. New York: Lange Medical Books/McGraw-Hill, 256. ISBN 0-8385-0598-8.
- ↑ Heran BS, Chen JM, Wang JJ, Wright JM (2010). "Blood pressure lowering efficacy of potassium-sparing diuretics (that block the epithelial sodium channel) for primary hypertension.". Cochrane Database Syst Rev (1): CD008167. DOI:10.1002/14651858.CD008167.pub2. PMID 20091662. Research Blogging.
- ↑ Gheorghiade M et al. Short-term clinical effects of tolvaptan, an oral vasopressin antagonist, in patients hospitalized for heart failure: the EVEREST Clinical Status Trials. JAMA 2007;297:1332-43. Epub 2007 Mar 25. PMID 17384438
- ↑ Konstam MA et al. Effects of oral tolvaptan in patients hospitalized for worsening heart failure: the EVEREST Outcome Trial. JAMA 2007;297:1319-31. Epub 2007 Mar 25. PMID 17384437
- ↑ Goldsmith SR, Gheorghiade M. Vasopressin antagonism in heart failure. J Am Coll Cardiol. 2005;46:1785-91. PMID 16286160
- ↑ 13.0 13.1 Colucci WS, et al. Intravenous nesiritide, a natriuretic peptide, in the treatment of decompensated congestive heart failure. Nesiritide Study Group. N Engl J Med. 2000 Jul 27;343(4):246-53. Erratum in: N Engl J Med 2000 Nov 16;343(20):1504. N Engl J Med 2000;343:896. PMID 10911006
- ↑ 14.0 14.1 Brater DC (August 1998). "Diuretic therapy". N. Engl. J. Med. 339 (6): 387–95. PMID 9691107. [e]
- ↑ Wollam GL, Tarazi RC, Bravo EL, Dustan HP (June 1982). "Diuretic potency of combined hydrochlorothiazide and furosemide therapy in patients with azotemia". Am. J. Med. 72 (6): 929–38. PMID 7046434. [e]
- ↑ Fliser D, Schröter M, Neubeck M, Ritz E (August 1994). "Coadministration of thiazides increases the efficacy of loop diuretics even in patients with advanced renal failure". Kidney Int. 46 (2): 482–8. PMID 7967362. [e]
- ↑ Knauf H, Mutschler E (September 1995). "Diuretic effectiveness of hydrochlorothiazide and furosemide alone and in combination in chronic renal failure". J. Cardiovasc. Pharmacol. 26 (3): 394–400. PMID 8583780. [e]
- ↑ 18.0 18.1 Siscovick DS, Raghunathan TE, Psaty BM, et al (June 1994). "Diuretic therapy for hypertension and the risk of primary cardiac arrest". N. Engl. J. Med. 330 (26): 1852–7. PMID 8196728. [e]