- Phenylbutazone
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Phenylbutazone 
Systematic (IUPAC) name 4-butyl-1,2-diphenyl-pyrazolidine-3,5-dione Clinical data Trade names Butazolidine Pregnancy cat. ? Legal status ℞ Prescription only Identifiers CAS number 50-33-9 
ATC code M01AA01 M02AA01 PubChem CID 4781 DrugBank APRD00409 ChemSpider 4617 UNII GN5P7K3T8S KEGG D00510 ChEBI CHEBI:48574 
ChEMBL CHEMBL101 Chemical data Formula C19H20N2O2 Mol. mass 308.374 g/mol SMILES eMolecules & PubChem - InChI=1S/C19H20N2O2/c1-2-3-14-17-18(22)20(15-10-6-4-7-11-15)21(19(17)23)16-12-8-5-9-13-16/h4-13,17H,2-3,14H2,1H3
Key:VYMDGNCVAMGZFE-UHFFFAOYSA-N
(what is this?) (verify)Phenylbutazone, often referred to as bute,[citation needed] is a non-steroidal anti-inflammatory drug (NSAID) for the short-term treatment of pain and fever in animals. In the United States, it is no longer approved for human use.
Contents
Uses
In humans
Phenylbutazone was originally made available for use in humans for the treatment of rheumatoid arthritis and gout in 1949. However, it is no longer approved, and therefore not marketed, for any human use in the United States.[1]
In horses
Phenylbutazone is commonly used in horses for the following purposes:
- Analgesia: It is used for pain relief from infections and musculoskeletal disorders, including sprains, overuse injuries, tendinitis, arthralgias, arthritis, and laminitis. Like other NSAIDs, it acts directly on musculoskeletal tissue to control inflammation, thereby reducing secondary inflammatory damage, alleviating pain, and restoring range of motion. It does not cure musculoskeletal ailments or work well on colic pain.
- Antipyresis: It is used for reduction of fevers. Its antipyretic qualities may mask other symptoms; therefore, it should not be administered for this purpose unless a veterinarian has concluded the horse would not be able to eat or drink without its use or that the fever might hinder the horse's recovery.
History of phenylbutazone in racing
In the 1968 Kentucky Derby, Dancer's Image, the winner of the race, was disqualified after traces of phenylbutazone were discovered in a postrace urinalysis. Owned by prominent Massachusetts businessman Peter Fuller and jockeyed by Bobby Ussery, Dancer's Image remains the only horse to win the Kentucky Derby and then be disqualified. Phenylbutazone was legal on most tracks around the country in 1968, but had not yet been approved by Churchill Downs.
Controversy and speculation still surrounds the incident. In the weeks prior to the race, Peter Fuller had given previous winnings to Coretta Scott King, the widow of slain civil rights activist Martin Luther King Jr., which brought both praise and criticism. The previous year, King held a sit-in against housing discrimination which disrupted Derby week. Forty years later, Fuller still believes Dancer's Image was disqualified due to these events.[2][3]
Although after many appeals, Forward Pass was named the winner, the Kentucky Derby official website lists both Dancer's Image and Forward Pass as the winner. The website's race video commentary states that on the winner's plaque at Churchill Downs, both Dancer's Image and Forward Pass are listed as the 1968 winner of the Kentucky Derby.[4]
In dogs
Phenylbutazone is occasionally used in dogs for the longer-term management of chronic pain, particularly due to osteoarthritis. About 20% of adult dogs are affected with osteoarthritis, which makes the management of musculoskeletal pain a major component of companion animal practice. There is a very narrow margin of safety for all NSAIDs in the dog, and other NSAIDs are more commonly used (etodolac, and carprofen). Gastrointestinal-protectant drugs, such as misoprostol, cimetidine, omeprazole, ranitidine, or sucralfate, are frequently included as a part of treatment with any NSAID. Dogs receiving chronic phenylbutazone therapy should be followed with regular blood work and renal monitoring.[5]
Side effects of phenylbutazone in dogs include GI ulceration, bone marrow depression, rashes, malaise, blood dyscrasias, and diminished renal blood flow.
Dosage and administration
Phenylbutazone may be administered orally (via paste, powder or feed-in) or intravenously. It should not be given intramuscularly or injected in any place other than a vein, as it can cause tissue damage. Tissue damage and edema may also occur if the drug is injected repetitively into the same vein.
Phenylbutazone should be administered only under the advice of a veterinarian.
Side effects and disadvantages
Side effects of phenylbutazone are similar to those of other NSAIDs. Overdose or prolonged use can cause gastrointestinal (GI) ulcers, blood dyscrasia, kidney damage, oral lesions, and internal hemorrhage, especially pronounced in young, ill, or stressed horses. Effects of GI damage include edema of the legs and belly secondary to leakage of blood proteins into the intestines, resulting in decreased appetite, excessive thirst, weight loss, weakness, and in advanced stages, kidney failure and death.
Phenylbutazone should not be used in combination with blood thinners (e.g., coumadin), as it amplifies the anticoagulant effects of these drugs; with other NSAIDs (all NSAIDs are additive); or in horses with known kidney or liver problems.
Periodic blood tests are recommended when using phenylbutazone as agranulocytosis can occur.
Phenylbutazone should be used cautiously in pregnant or nursing mares, as it may be toxic to the embryo and can be transferred via the umbilical cord and by milk.
Phenylbutazone may be used in foals, but it should be used with particular caution. Premature foals, septicemic foals, foals with questionable kidney or liver function and foals with diarrhea require careful monitoring. Drugs to protect the GI tract such as omeprazole, cimetidine, and sucralfate are frequently used with phenylbutazone.
High doses of phenylbutazone may be considered a rules violation under some equestrian organizations, as the drug may remain in the bloodstream four to five days after administration.
The International Agency for Research on Cancer (IARC) places it in Group 3; i.e., "not classifiable as to its carcinogenicity to humans".
Use in horses is limited to horses which are not intended for food. Metabolites of phenylbutazone can cause aplastic anaemia in humans.[6][7]
Interactions
Other anti-inflammatory drugs that tend to cause GI ulcers, such as corticosteroids and other NSAIDs, can potentiate the bleeding risk. Combination with anticoagulant drugs, particularly coumarin derivatives, also increases the risk of bleeding. Avoid combining with other hepatotoxic drugs.
Phenylbutazone may affect blood levels and duration of action of phenytoin, valproic acid, sulfonamides, sulfonylurea antidiabetic agents, barbiturates, promethazine, rifampicin, chlorpheniramine, diphenhydramine, penicillin G.[8]
Overdose
Overdoses of phenylbutazone can cause renal failure, liver injury, bone marrow suppression, and gastric ulceration or perforation. Early signs of toxicity include loss of appetite, and depression.[8]
Chemistry
Phenylbutazone is a crystalline substance. It is obtained by condensation of diethyl n-butylmalonate with hydrazobenzene in the presence of base. In effect, this represents the formation of the heterocyclic system by simple lactamization.
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Hydrazobenzene
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Diethyl n-butylmalonate
Oxyphenbutazone, the major metabolite of phenylbutazone, differs only in the para location of one of its phenyl groups, where a hydrogen atom is replaced by a hydroxyl group (making it 4-butyl-1-(4-hydroxyphenyl)-2-phenyl-3,5-pyrazolidinedione).
References
- ^ "FDA Order Prohibits Extralabel Use of Phenylbutazone in Certain Dairy Cattle". Food and Drug Administration. 28 February 2003. http://www.fda.gov/AnimalVeterinary/NewsEvents/CVMUpdates/ucm124078.htm.
- ^ Boston Globe article about the 40th Anniversary of the Race
- ^ "Sports: Dancer's tainted image". http://www.seacoastonline.com/1999news/4_25_s1.htm. Retrieved 2007-10-07.
- ^ "Kentucky Derby 132". 2006. http://www.kentuckyderby.com/2006/derby_history/derby_charts/years/1968.html. Retrieved 2007-10-07.
- ^ "Wedgewood Pharmaceuticals-Phenylbutazol". http://www.wedgewoodpharmacy.com/monographs/phenylbutazone.asp.
- ^ Peadar Ó Scanaill. "Phenylbutazone and its availability in ireland – prudent prescribing and dispensing". Irish Veterinary Journal 63 (12): 766–8. http://www.veterinaryirelandjournal.com/Links/PDFs/CE-Large/CELA_Dec_2010.pdf.pdf.
- ^ "Ante and Post-mortem Procedures, Dispositions, Monitoring and Controls - Red Meat Species, Ostriches, Rheas and Emus". Canadian Food Inspection Agency. http://www.inspection.gc.ca/english/fssa/meavia/man/ch17/annexee.shtml.
- ^ a b "Phenylbutazol for veterinary use". Wedgewood Pharmacy. http://www.wedgewoodpharmacy.com/monographs/phenylbutazone.asp.
Anti-inflammatory products (M01A) Pyrazolidine/Butylpyrazolidines Ampyrone • Clofezone • Kebuzone • Metamizole • Mofebutazone • Oxyphenbutazone • Phenazone • Phenylbutazone • Sulfinpyrazone • Feprazone •Acetic acid derivatives
and related substancesAceclofenac • Acemetacin • Alclofenac • Bromfenac • Bumadizone • Bufexamac • Diclofenac • Difenpiramide • Etodolac • Fentiazac • Indometacin • Ketorolac • Lonazolac • Oxametacin • Proglumetacin • Sulindac • Tolmetin • Zomepirac • AmfenacOxicams Propionic acid derivatives Alminoprofen • Benoxaprofen • Dexibuprofen • Dexketoprofen • Fenbufen • Fenoprofen • Flunoxaprofen • Flurbiprofen • Ibuprofen • Ibuproxam • Indoprofen • Ketoprofen • Naproxen • Oxaprozin • Pirprofen • Suprofen • Tiaprofenic acidFenamates Coxibs Other Topical products for joint and muscular pain (M02) Anti-inflammatory preparations,
non-steroidsAcetic acid derivativesOtherBenzydamine • Etofenamate • Piroxicam • Felbinac • Bufexamac • Ketoprofen • Bendazac • Naproxen • Ibuprofen • Feprazone • Niflumic acid • Meclofenamic acid • Flurbiprofen • Suxibuzone • Indometacin • NifenazoneCapsaicin derivatives Other Tolazoline • Dimethyl sulfoxide • IdrocilamideCategories:- Non-steroidal anti-inflammatory drugs
- Equine medications
- Pyrazolidindiones
- InChI=1S/C19H20N2O2/c1-2-3-14-17-18(22)20(15-10-6-4-7-11-15)21(19(17)23)16-12-8-5-9-13-16/h4-13,17H,2-3,14H2,1H3
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