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acting to increase the excretion of uric acid in the urine

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/07/19 10:24:04」(JST)

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Uricosuric medications (drugs) are substances that increase the excretion of uric acid in the urine, thus reducing the concentration of uric acid in blood plasma. In general, this effect is achieved by action on the proximal tubule of the kidney. Drugs that reduce blood uric acid are not all uricosurics; blood uric acid can be reduced by other mechanisms (see other Antigout medications).

Uricosurics are often used in the treatment of gout, a disease in which uric acid crystals form deposits in the joints. By decreasing plasma uric acid levels, uricosurics help dissolve these crystals, while limiting the formation of new ones. However, the increased uric acid levels in urine can contribute to kidney stones. Thus, use of these drugs is contraindicated in persons already with a high urine concentration of uric acid (hyperuricosuria). In borderline cases, enough water to produce 2 liters of urine per day may be sufficient to permit use of an uricosuric drug.

By their mechanism of action, some uricosurics (such as probenecid) increase the blood plasma concentration of certain other drugs and their metabolic products. While this is occasionally exploitable to good effect (see oseltamivir), assessment of drug interactions is very important when using uricosuric drugs in the presence of other medications.

Primary uricosurics[edit]

The primary uricosuric drugs include probenecid, benzbromarone and sulfinpyrazone.

Secondary uricosurics[edit]

Drugs with other primary uses, that have known uricosuric properties, include guaifenesin,^[1] losartan,^[2] atorvastatin, and fenofibrate. Although these drugs may have significant uricosuric action, their other significant pharmacological actions in off-label use as a uricosuric requires careful assessment of the patient to achieve the most benefit and least risk.^[3]^[4]

Amlodipine
Atorvastatin (lowers cholesterol)
Fenofibrate (lowers triglycerides, raises HDL)
Guaifenesin (expectorant)
Losartan
Adrenocorticotropic hormone^[5]
Cortisone^[5]

Abdominal surgery also has a uricosuric effect, as well as the potential to precipitate an acute attack of gout.^[5]

Pharmacology[edit]

In general, uricosuric drugs act on the proximal tubules in the kidneys, where they interfere with the absorption of uric acid from the kidney back into the blood. Several uricosurics are known to act in vitro by blocking the function of a protein encoded by the gene SLC22A12, also known as urate transporter 1 or URAT1. URAT1 is the central mediator in the transport of uric acid from the kidney into the blood. In some persons with loss-of-function mutations of URAT1, the uricosurics benzbromarone and losartan had no effect, suggesting these drugs act on URAT1 in vivo.^[2] Thus, uricosuric drugs may be candidates for management in a personalized medicine model.

Antiuricosurics[edit]

Antiuricosuric drugs raise serum uric acid levels and lower urine uric acid levels. These drugs include all diuretics,^{[citation needed]} pyrazinoate, pyrazinamide, ethambutol, and aspirin. The NSAID diclofenac has an antiuricosuric action, which may be partly responsible for the extraordinary toxicity of this drug in vultures.^[6]

Pyrazinamide, a drug indicated only for treatment of tuberculosis, is a potent antiuricosuric^[7] and, as a consequence, has an off-label use in the diagnosis of causes of abnormal uric acid clearance.^[8] It acts on URAT1.^[8]

Antiuricosuric drugs are useful for treatment of hypouricemia and perhaps also hyperuricosuria, but are contraindicated in persons with conditions including hyperuricemia and gout.

External links[edit]

604373033 at GPnotebook
Uricosuric agents at the US National Library of Medicine Medical Subject Headings (MeSH)

References[edit]

^ Ramsdell CM, Postlethwaite AE, Kelley WN (March 1974). "Uricosuric effect of glyceryl guaiacolate". The Journal of rheumatology 1 (1): 114–6. PMID 4617771.
^ ^a ^b Hamada T, Ichida K, Hosoyamada M, Mizuta E, Yanagihara K, Sonoyama K, Sugihara S, Igawa O, Hosoya T, Ohtahara A, Shigamasa C, Yamamoto Y, Ninomiya H, Hisatome I (October 2008). "Uricosuric action of losartan via the inhibition of urate transporter 1 (URAT 1) in hypertensive patients". Am. J. Hypertens. 21 (10): 1157–62. doi:10.1038/ajh.2008.245. PMID 18670416.
^ Lee SJ, Terkeltaub RA (June 2006). "New developments in clinically relevant mechanisms and treatment of hyperuricemia". Curr Rheumatol Rep 8 (3): 224–30. doi:10.1007/s11926-996-0029-z. PMID 16901081.
^ Daskalopoulou SS, Tzovaras V, Mikhailidis DP, Elisaf M (2005). "Effect on serum uric acid levels of drugs prescribed for indications other than treating hyperuricaemia". Curr. Pharm. Des. 11 (32): 4161–75. doi:10.2174/138161205774913309. PMID 16375738.
^ ^a ^b ^c Snaith ML, Scott JT (May 1972). "Uric acid excretion and surgery". Ann. Rheum. Dis. 31 (3): 162–5. doi:10.1136/ard.31.3.162. PMC 1005890. PMID 5032447.
^ Naidoo V, Swan GE (August 2008). "Diclofenac toxicity in Gyps vulture is associated with decreased uric acid excretion and not renal portal vasoconstriction". Comp. Biochem. Physiol. C Toxicol. Pharmacol. 149 (3): 269–74. doi:10.1016/j.cbpc.2008.07.014. PMID 18727958.
^ Spaia S, Magoula I, Tsapas G, Vayonas G (2000). "Effect of pyrazinamide and probenecid on peritoneal urate transport kinetics during continuous ambulatory peritoneal dialysis". Perit Dial Int 20 (1): 47–52. PMID 10716583.
^ ^a ^b Ichida K, Hosoyamada M, Hisatome I, Enomoto A, Hikita M, Endou H, Hosoya T (January 2004). "Clinical and molecular analysis of patients with renal hypouricemia in Japan-influence of URAT1 gene on urinary urate excretion". J. Am. Soc. Nephrol. 15 (1): 164–73. doi:10.1097/01.ASN.0000105320.04395.D0. PMID 14694169.

UpToDate Contents

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1. Prevention of recurrent gout: Pharmacologic urate-lowering therapy and treatment of tophi
2. 尿酸腎結石症 uric acid nephrolithiasis
3. 利尿剤によって誘発された高尿酸血症および痛風 diuretic induced hyperuricemia and gout
4. 低尿酸血症：原因および臨床的意義 hypouricemia causes and clinical significance
5. Prevention of recurrent gout: Lifestyle modification and other strategies for risk reduction

English Journal

The History and Future of Probenecid.

Robbins N, Koch SE, Tranter M, Rubinstein J.SourceDepartment of Internal Medicine, Division of Cardiovascular Diseases, College of Medicine, University of Cincinnati, 231 Albert Sabin Way ML0542, Cincinnati, OH, 45267, USA.
Cardiovascular toxicology.Cardiovasc Toxicol.2011 Sep 22. [Epub ahead of print]
Probenecid was initially developed with the goal of reducing the renal excretion of antibiotics, specifically penicillin. It is still used for its uricosuric properties in the treatment in gout, but its clinical relevance has sharply fallen and is rarely used today for either. Interestingly, through
PMID 21938493

Quercetin regulates organic ion transporter and uromodulin expression and improves renal function in hyperuricemic mice.

Hu QH, Zhang X, Wang X, Jiao RQ, Kong LD.SourceState Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210093, People's Republic of China.
European journal of nutrition.Eur J Nutr.2011 Sep 10. [Epub ahead of print]
BACKGROUND: Renal organic ion transporters and uromodulin (UMOD) play the important roles in renal urate excretion and function. Hyperuricemia is considered as a risk factor for the development of renal dysfunction. The flavonoid quercetin in diets exerts the hypouricemic and nephroprotective effect
PMID 21909718

Japanese Journal

Benzbromarone Pharmacokinetics and Pharmacodynamics in Different Cytochrome P450 2C9 Genotypes

UCHIDA Shinya,SHIMADA Kayoko,MISAKA Shingen,IMAI Hiromitsu,KATOH Yasuhiro,INUI Naoki,TAKEUCHI Kazuhiko,ISHIZAKI Takashi,YAMADA Shizuo,OHASHI Kyoichi,NAMIKI Noriyuki,WATANABE Hiroshi
Drug metabolism and pharmacokinetics 25(6), 605-610, 2010-12-25
NAID 10027743998

Renal Secretion of Uric Acid by Organic Anion Transporter 2 (OAT2/SLC22A7) in Human

Sato Masanobu,Mamada Hideaki,Anzai Naohiko,Shirasaka Yoshiyuki,Nakanishi Takeo,Tamai Ikumi
Biological & Pharmaceutical Bulletin 33(3), 498-503, 2010
The physiological function of organic anion transporter OAT2 (SLC22A7) remains unclear, but since OAT2 transports purine derivatives, it may be involved in renal handling of uric acid, the final metab …
NAID 130000248105