Uricosuric
Encyclopedia
Uricosuric medication
s (drug
s) 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
. Drugs that reduce blood uric acid are not all uricosurics; blood uric acid can be reduced by other mechanisms (see other ).
Uricosurics are often used in the treatment of gout
, a disease
in which uric acid crystals form deposits in the joint
s. 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.
, benzbromarone
and sulfinpyrazone
.
, losartan
, 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.
Abdominal surgery
also has a uricosuric effect, as well as the potential to precipitate an acute attack of gout.
s in the kidney
s, 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
. Thus, uricosuric drugs may be candidates for management in a personalized medicine
model.
s, 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 vulture
s.
Pyrazinamide, a drug indicated
only for treatment of tuberculosis
, is a potent antiuricosuric and, as a consequence, has an off-label use
in the diagnosis of causes of abnormal uric acid clearance. It acts on URAT1.
Antiuricosuric drugs are useful for treatment of hypouricemia
and perhaps also hyperuricosuria
, but are contraindicated in persons with conditions including hyperuricemia
and gout
.
Medication
A pharmaceutical drug, also referred to as medicine, medication or medicament, can be loosely defined as any chemical substance intended for use in the medical diagnosis, cure, treatment, or prevention of disease.- Classification :...
s (drug
Drug
A drug, broadly speaking, is any substance that, when absorbed into the body of a living organism, alters normal bodily function. There is no single, precise definition, as there are different meanings in drug control law, government regulations, medicine, and colloquial usage.In pharmacology, a...
s) are substances that increase the excretion of uric acid
Uric acid
Uric acid is a heterocyclic compound of carbon, nitrogen, oxygen, and hydrogen with the formula C5H4N4O3. It forms ions and salts known as urates and acid urates such as ammonium acid urate. Uric acid is created when the body breaks down purine nucleotides. High blood concentrations of uric acid...
in the urine
Urine
Urine is a typically sterile liquid by-product of the body that is secreted by the kidneys through a process called urination and excreted through the urethra. Cellular metabolism generates numerous by-products, many rich in nitrogen, that require elimination from the bloodstream...
, thus reducing the concentration of uric acid in blood plasma
Blood plasma
Blood plasma is the straw-colored liquid component of blood in which the blood cells in whole blood are normally suspended. It makes up about 55% of the total blood volume. It is the intravascular fluid part of extracellular fluid...
. In general, this effect is achieved by action on the proximal tubule
Proximal tubule
The proximal tubule is the portion of the duct system of the nephron of the kidney which leads from Bowman's capsule to the loop of Henle.-Structure and appearance:...
. Drugs that reduce blood uric acid are not all uricosurics; blood uric acid can be reduced by other mechanisms (see other ).
Uricosurics are often used in the treatment of gout
Gout
Gout is a medical condition usually characterized by recurrent attacks of acute inflammatory arthritis—a red, tender, hot, swollen joint. The metatarsal-phalangeal joint at the base of the big toe is the most commonly affected . However, it may also present as tophi, kidney stones, or urate...
, a disease
Disease
A disease is an abnormal condition affecting the body of an organism. It is often construed to be a medical condition associated with specific symptoms and signs. It may be caused by external factors, such as infectious disease, or it may be caused by internal dysfunctions, such as autoimmune...
in which uric acid crystals form deposits in the joint
Joint
A joint is the location at which two or more bones make contact. They are constructed to allow movement and provide mechanical support, and are classified structurally and functionally.-Classification:...
s. 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
Contraindication
In medicine, a contraindication is a condition or factor that serves as a reason to withhold a certain medical treatment.Some contraindications are absolute, meaning that there are no reasonable circumstances for undertaking a course of action...
in persons already with a high urine concentration of uric acid (hyperuricosuria
Hyperuricosuria
Hyperuricosuria is a medical term referring to the presence of excessive amounts of uric acid in the urine. Notable direct causes of hyperuricosuria are dissolution of uric acid crystals in the kidneys or urinary bladder, and hyperuricemia...
). 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
Probenecid
Probenecid is a uricosuric drug that increases uric acid excretion in the urine. It is primarily used in treating gout and hyperuricemia.Probenecid was developed as an alternative to caronamide...
) increase the blood plasma concentration of certain other drugs and their metabolic products. While this is occasionally exploitable to good effect (see oseltamivir
Oseltamivir
Oseltamivir INN , an antiviral drug, slows the spread of influenza virus between cells in the body by stopping the virus from chemically cutting ties with its host cell; median time to symptom alleviation is reduced by 0.5–1 day. The drug is sold under the trade name Tamiflu, and is taken orally...
), assessment of drug interactions is very important when using uricosuric drugs in the presence of other medications.
Primary uricosurics
The primarily uricosuric drugs include probenecidProbenecid
Probenecid is a uricosuric drug that increases uric acid excretion in the urine. It is primarily used in treating gout and hyperuricemia.Probenecid was developed as an alternative to caronamide...
, benzbromarone
Benzbromarone
Benzbromarone is a uricosuric agent used in the treatment of gout, especially when allopurinol, a first-line treatment, fails or produces intolerable adverse effects...
and sulfinpyrazone
Sulfinpyrazone
Sulfinpyrazone is a uricosuric medication used to treat gout. It also sometimes is used to reduce platelet aggregation by inhibiting degranulation of platelets which reduces the release of ADP and thromboxane....
.
Secondary uricosurics
Drugs with other primary uses, that have known uricosuric properties, include guaifenesinGuaifenesin
Guaifenesin INN or guaiphenesin , also glyceryl guaiacolate, is an expectorant drug sold over the counter and usually taken by mouth to assist the bringing up of phlegm from the airways in acute respiratory tract infections.-History:Similar medicines derived from the guaiac tree were in use as a...
, losartan
Losartan
Losartan is an angiotensin II receptor antagonist drug used mainly to treat high blood pressure . Losartan was the first angiotensin II receptor antagonist to be marketed. Losartan potassium is marketed by Merck & Co. Inc. under the trade name Cozaar...
, atorvastatin
Atorvastatin
Atorvastatin , sold by Pfizer under the trade name Lipitor, is a member of the drug class known as statins, used for lowering blood cholesterol. It also stabilizes plaque and prevents strokes through anti-inflammatory and other mechanisms...
, and fenofibrate
Fenofibrate
Fenofibrate is a drug of the fibrate class. Fenofibrate was developed by Groupe Fournier SA, before it was acquired in 2005 by Solvay Pharmaceutical, a business unit owned by the Belgian corporation, Solvay S.A. In 2009 Solvay Pharmaceutical was acquired by Abbott Laboratories. It is mainly used to...
. Although these drugs may have significant uricosuric action, their other significant pharmacological actions in off-label use
Off-label use
Off-label use is the practice of prescribing pharmaceuticals for an unapproved indication or in an unapproved age group, unapproved dose or unapproved form of administration...
as a uricosuric requires careful assessment of the patient to achieve the most benefit and least risk.
- AmlodipineAmlodipineAmlodipine is a long-acting calcium channel blocker used as an anti-hypertensive and in the treatment of angina...
- AtorvastatinAtorvastatinAtorvastatin , sold by Pfizer under the trade name Lipitor, is a member of the drug class known as statins, used for lowering blood cholesterol. It also stabilizes plaque and prevents strokes through anti-inflammatory and other mechanisms...
(lowers cholesterolCholesterolCholesterol is a complex isoprenoid. Specifically, it is a waxy steroid of fat that is produced in the liver or intestines. It is used to produce hormones and cell membranes and is transported in the blood plasma of all mammals. It is an essential structural component of mammalian cell membranes...
) - FenofibrateFenofibrateFenofibrate is a drug of the fibrate class. Fenofibrate was developed by Groupe Fournier SA, before it was acquired in 2005 by Solvay Pharmaceutical, a business unit owned by the Belgian corporation, Solvay S.A. In 2009 Solvay Pharmaceutical was acquired by Abbott Laboratories. It is mainly used to...
(lowers triglycerides, raises HDL) - GuaifenesinGuaifenesinGuaifenesin INN or guaiphenesin , also glyceryl guaiacolate, is an expectorant drug sold over the counter and usually taken by mouth to assist the bringing up of phlegm from the airways in acute respiratory tract infections.-History:Similar medicines derived from the guaiac tree were in use as a...
(expectorant) - LosartanLosartanLosartan is an angiotensin II receptor antagonist drug used mainly to treat high blood pressure . Losartan was the first angiotensin II receptor antagonist to be marketed. Losartan potassium is marketed by Merck & Co. Inc. under the trade name Cozaar...
- Adrenocorticotropic hormoneAdrenocorticotropic hormoneAdrenocorticotropic hormone , also known as 'corticotropin', 'Adrenocorticotrophic hormone', is a polypeptide tropic hormone produced and secreted by the anterior pituitary gland. It is an important component of the hypothalamic-pituitary-adrenal axis and is often produced in response to biological...
- CortisoneCortisoneCortisone is a steroid hormone. It is one of the main hormones released by the adrenal gland in response to stress. In chemical structure, it is a corticosteroid closely related to corticosterone. It is used to treat a variety of ailments and can be administered intravenously, orally,...
Abdominal surgery
Surgery
Surgery is an ancient medical specialty that uses operative manual and instrumental techniques on a patient to investigate and/or treat a pathological condition such as disease or injury, or to help improve bodily function or appearance.An act of performing surgery may be called a surgical...
also has a uricosuric effect, as well as the potential to precipitate an acute attack of gout.
Pharmacology
In general, uricosuric drugs act on the proximal tubuleProximal tubule
The proximal tubule is the portion of the duct system of the nephron of the kidney which leads from Bowman's capsule to the loop of Henle.-Structure and appearance:...
s in the kidney
Kidney
The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...
s, where they interfere with the absorption of uric acid from the kidney back into the blood. Several uricosurics are known to act in vitro
In vitro
In vitro refers to studies in experimental biology that are conducted using components of an organism that have been isolated from their usual biological context in order to permit a more detailed or more convenient analysis than can be done with whole organisms. Colloquially, these experiments...
by blocking the function of a protein encoded by the gene SLC22A12
SLC22A12
Solute carrier family 22 , member 12, also known as SLC22A12 and URAT1, is a protein which in humans is encoded by the SLC22A12 gene.-Function:...
, 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
In vivo
In vivo is experimentation using a whole, living organism as opposed to a partial or dead organism, or an in vitro controlled environment. Animal testing and clinical trials are two forms of in vivo research...
. Thus, uricosuric drugs may be candidates for management in a personalized medicine
Personalized medicine
Personalized medicine is a medical model emphasizing in general the customization of healthcare, with all decisions and practices being tailored to individual patients in whatever ways possible...
model.
Antiuricosurics
Antiuricosuric drugs raise serum uric acid levels and lower urine uric acid levels. These drugs include all diureticDiuretic
A diuretic provides a means of forced diuresis which elevates the rate of urination. There are several categories of diuretics. All diuretics increase the excretion of water from bodies, although each class does so in a distinct way.- Medical uses :...
s, pyrazinoate, pyrazinamide
Pyrazinamide
Pyrazinamide is a drug used to treat tuberculosis. The drug is largely bacteriostatic, but can be bacteriocidal on actively replicating tuberculosis bacteria.-Abbreviations:...
, ethambutol
Ethambutol
Ethambutol is a bacteriostatic antimycobacterial drug prescribed to treat tuberculosis. It is usually given in combination with other tuberculosis drugs, such as isoniazid, rifampicin and pyrazinamide....
, and aspirin
Aspirin
Aspirin , also known as acetylsalicylic acid , is a salicylate drug, often used as an analgesic to relieve minor aches and pains, as an antipyretic to reduce fever, and as an anti-inflammatory medication. It was discovered by Arthur Eichengrun, a chemist with the German company Bayer...
. The NSAID diclofenac
Diclofenac
Diclofenac is a non-steroidal anti-inflammatory drug taken to reduce inflammation and as an analgesic reducing pain in certain conditions....
has an antiuricosuric action, which may be partly responsible for the extraordinary toxicity
Toxicity
Toxicity is the degree to which a substance can damage a living or non-living organisms. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a substructure of the organism, such as a cell or an organ , such as the liver...
of this drug in vulture
Vulture
Vulture is the name given to two groups of convergently evolved scavenging birds, the New World Vultures including the well-known Californian and Andean Condors, and the Old World Vultures including the birds which are seen scavenging on carcasses of dead animals on African plains...
s.
Pyrazinamide, a drug indicated
Indication (medicine)
In medicine, an indication is a valid reason to use a certain test, medication, procedure, or surgery. The opposite of indication is contraindication.-Drugs:...
only for treatment of tuberculosis
Tuberculosis
Tuberculosis, MTB, or TB is a common, and in many cases lethal, infectious disease caused by various strains of mycobacteria, usually Mycobacterium tuberculosis. Tuberculosis usually attacks the lungs but can also affect other parts of the body...
, is a potent antiuricosuric and, as a consequence, has an off-label use
Off-label use
Off-label use is the practice of prescribing pharmaceuticals for an unapproved indication or in an unapproved age group, unapproved dose or unapproved form of administration...
in the diagnosis of causes of abnormal uric acid clearance. It acts on URAT1.
Antiuricosuric drugs are useful for treatment of hypouricemia
Hypouricemia
Hypouricemia is a level of uric acid in blood serum that is below normal. In humans, the normal range of this blood component has a lower threshold set variously in the range of 2 mg/dL to 4 mg/dL, while the upper threshold is 530 micromol/L for women and 619 micromol/L for men...
and perhaps also hyperuricosuria
Hyperuricosuria
Hyperuricosuria is a medical term referring to the presence of excessive amounts of uric acid in the urine. Notable direct causes of hyperuricosuria are dissolution of uric acid crystals in the kidneys or urinary bladder, and hyperuricemia...
, but are contraindicated in persons with conditions including hyperuricemia
Hyperuricemia
Hyperuricemia is a level of uric acid in the blood that is abnormally high. In humans, the upper end of the normal range is 360 µmol/L for women and 400 µmol/L for men.-Causes:...
and gout
Gout
Gout is a medical condition usually characterized by recurrent attacks of acute inflammatory arthritis—a red, tender, hot, swollen joint. The metatarsal-phalangeal joint at the base of the big toe is the most commonly affected . However, it may also present as tophi, kidney stones, or urate...
.