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Phenylbutazone

Phenylbutazone
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Systematic (IUPAC) name
4-butyl-1,2-diphenyl-pyrazolidine-3,5-dione
Identifiers
CAS number 50-33-9
ATC code M01AA01 M02AA01
PubChem CID 4781
DrugBank APRD00409
Chemical data
Formula Template:OrganicBox atomTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBox 
Mol. mass 308.374 g/mol
Therapeutic considerations
Pregnancy cat.  ?
Legal status Prescription only
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Phenylbutazone, often referred to as bute, is a crystalline substance having the structure shown at right.

  • Structural name: 4-butyl-1,2-diphenyl-3,5-pyrazolidinedione
  • Chemical formula: C19H20N2O2Oxyphenbutazone, 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).

Despite its name, phenylbutazone is chemically unrelated to the class of chemicals known as benzones (common examples include oxybenzone, dioxybenzone, avobenzone, and sulisobenzone), which are used as active ingredients in sunscreen formulations for protection against UVB rays.

Phenylbutazone is used as a non-steroidal anti-inflammatory drug (NSAID) for the treatment of chronic pain, including the symptoms of arthritis. Its use is limited by such severe side effects as suppression of white blood cell production and aplastic anemia.

The International Agency for Research on Cancer (IARC) places it in Group 3; i.e., "not classifiable as to its carcinogenicity to humans."

Contents

Uses of phenylbutazone in horses

Phenylbutazone is an NSAID commonly used in horses for the following purposes:

  • Analgesia: Pain relief from infections and musculoskeletal disorders including sprains, overuse injuries, tendinitis, arthralgias, arthritis, and laminitis. Like other NSAIDs, acts directly on musculoskeletal tissue to control inflammation, thereby reducing secondary inflammatory damage, alleviating pain, and restoring range of motion. Does not cure musculoskeletal ailments or work well on colic pain.
  • Antipyresis: Reduction of fevers. Antipyretic qualities may mask other symptoms; therefore, should not be administered for this purpose unless a veterinarian has concluded that 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 post-race 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.[1][2]

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.[3]

Phenylbutazone for treatment 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 there are other NSAIDs that are more commonly used (etodolac, and carprofen). GI protectant drugs such as misprostal, 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.[4]

Side Effects of phenylbutazone in dogs: GI ulceration, bone marrow depression, rashes, malaise, blood dyscrasias, 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.

The maximum oral dose recommended by manufacturers is 2 to 4 grams per 1000 pounds of body weight (4 to 9 mg/kg) per day. Manufacturers recommend that the dose be divided equally and given every 8 hours for maximum results, although most horse owners give it every 12 to 24 hours for convenience, usually giving 1 to 2 grams in the morning and at night.

Intravenously, the maximum daily dose recommended by manufacturers is 1 to 2 grams per 1000 pounds (2 to 4.5 mg/kg). The maximum dose is usually given when the course of treatment is initiated, with the dosage subsequently being titrated down.

Phenylbutazone should be administered only under the advice of a veterinarian.

Side effects and disadvantages of phenylbutazone

Side effects of phenylbutazone are similar to that of other NSAIDs. Overdose or prolonged use can cause gastrointestinal ulcers, blood dyscrasia, kidney damage, oral lesions, and internal hemorrhage, especially pronounced in young, ill, or stressed horses. Effects of gastrointestinal 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 is obtained in straight forward manner 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

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. Periodically testing the blood may catch this issue before it is too late.

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.

In humans, Phenylbutazone is very dangerous, as it can cause aplastic anemia. The medicine should be given in a paste form to avoid contact with the medicine. Never breathe powder from crushing tablets.

Drug Interactions

Avoid combining with other anti-inflammatory drugs that tend to cause GI ulcers, such as corticosteroids and other NSAIDs. Avoid combining with anticoagulant drugs particularly coumarin derivatives. 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, rifampin, chlorpheniramine, diphenhydramine, penicillin G.[5]

Overdose

Overdoses of phenylbutazone can cause renal failure, liver injury, bone marrow suppression, and gastric ulceration/perforation. Early signs of toxicity include loss of appetite, and depression.[6]

References


External links



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