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 موضوع كامل عن الphenyl butazone

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مُساهمةموضوع: موضوع كامل عن الphenyl butazone   الخميس نوفمبر 05, 2009 12:07 am

موضوع كامل عن الphenyl butazone
PHENYLBUTAZONE
Chemistry - A synthetic pyrazolone derivative related chemically to aminopyrine, phenylbutazone
occurs as a white to off-white, odorless crystalline powder that has a pKa of 4.5. It is very slightly
soluble in water and 1 gram will dissolve in 28 ml of alcohol. It is tasteless at first, but has a slightly
bitter after-taste.
Storage/Stability/Compatibility - Oral products should be stored in tight, child-resistant containers
if possible. The injectable product should be stored in a cool place (46 - 56¡ F) or kept refrigerated.
Pharmacology - Phenylbutazone has analgesic, anti-inflammatory, antipyrexic, and mild uricosuric
properties. The proposed mechanism of action is by the inhibition of cyclooxygenase, thereby
reducing prostaglandin synthesis. Other pharmacologic actions phenylbutazone may induce include
reduced renal blood flow and decreased glomerular filtration rate, decreased platelet aggregation,
and gastric mucosal damage.
Pharmacokinetics - Following oral administration, phenylbutazone is absorbed from both the
stomach and small intestine. The drug is distributed throughout the body with highest levels attained
in the liver, heart, lungs, kidneys, and blood. Plasma protein binding in horses exceeds 99%.
Both phenylbutazone and oxyphenbutazone cross the placenta and are excreted into milk.
The serum half-life in the horse ranges from 3.5-6 hours, and like aspirin is dose-dependent.
Therapeutic efficacy however, may last for more than 24 hours however, probably due to the irreversible
binding of phenylbutazone to cyclooxygenase. In horses and other species, phenylbutazone
is nearly completely metabolized, primarily to oxphenbutazone (active) and gamma-hydroxyphenylbutazone.
Oxyphenbutazone has been detected in horse urine for up to 48 hours after a
single dose. Phenylbutazone is more rapidly excreted into alkaline than into acidic urine .
Other serum half-lives reported for animals are: Cattle » 40 - 55 hrs; Dogs » 2.5 - 6 hrs; Swine »
2 - 6 hrs.; Rabbits » 3 hrs..
Uses/Indications - One manufacturer lists the following as the indications for phenylbutazone:
ÒFor the relief of inflammatory conditions associated with the musculoskeletal system in dogs and
horses.Ó (Package Insert; Butazolidin¨ Ñ Coopers). It has been used primarily for the treatment
of lameness in horses and occasionally as an analgesic/anti-inflammatory, antipyrexic in dogs,
cattle, and swine.
Contraindications/Precautions - Phenylbutazone is contraindicated in patients with a history of,
or preexisting hematologic or bone marrow abnormalities, preexisting GI ulcers, and in food
producing animals or lactating dairy cattle. Cautious use in both foals and ponies is recommended
because of increased incidences of hypoproteinemia and GI ulceration. Foals with a heavy parasite
burden or that are undernourished may be more susceptible to development of adverse effects.
Phenylbutazone may cause decreased renal blood flow and sodium and water retention, and
should be used cautiously in animals with preexisting renal disease or CHF.
Because phenylbutazone may mask symptoms of lameness in horses for several days following
therapy, it can be used by unethical individuals to disguise lameness for ÒsoundnessÓ exams.
States may have different standards regarding the use of phenylbutazone in track animals. Complete
elimination of phenylbutazone in horses may take 2 months and it can be detected in the urine for at
least 7 days following administration.
Although phenylbutazone has shown no direct teratogenic effects, rodent studies have demonstrated
reduced litter sizes, increased neonatal mortality, and increased stillbirth rates.
Phenylbutazone should therefore be used in pregnancy only when the potential benefits of therapy
outweigh the risks associated with it.
Phenylbutazone is contraindicated in patients demonstrating previous hypersensitivity reactions to
it, and should be used very cautiously in patients that have a history of allergies to other drugs.
Adverse Effects/Warnings - The primary concerns with phenylbutazone therapy in humans include
its bone marrow effects (agranulocytosis, aplastic anemia), renal and cardiovascular effects
(fluid retention to acute renal failure), and GI effects (dyspepsia to perforated ulcers). Other serious
concerns with phenylbutazone include, hypersensitivity reactions, neurologic, dermatologic, and
hepatic toxicities.
While phenylbutazone is apparently a safer drug to use in horses and dogs than in people, serious
adverse reactions can still occur. Toxic effects that have been reported in horses include oral and GI
erosions and ulcers, hypoalbuminemia, diarrhea, anorexia, and renal effects (azotemia, renal
papillary necrosis). Unlike humans, it does not appear that phenylbutazone causes much sodium
and water retention in horses at usual doses, but edema has been reported. In dogs however,
phenylbutazone may cause sodium and water retention, and diminished renal blood flow.
Phenylbutazone-induced blood dyscrasias have also been reported in dogs.
Do not administer injectable preparation IM or SQ, as it is very irritating (swelling, to necrosis and
sloughing). Intracarotid injections may cause CNS stimulation and
seizures.Therapy should be halted at first signs of any toxic reactions
(e.g., anorexia, oral lesions, depression,
reduced plasma proteins, increased serum creatinine or BUN, leukopenia, or anemias).
The use of sucralfate or the H2 blockers (cimetidine, ranitidine) have been suggested for use in
treating the GI effects. Misoprostol, a prostaglandin E analog, may also be useful in reducing the
gastrointestinal effects of phenylbutazone.
Overdosage - Manifestations (human) of acute overdosage with phenylbutazone include, a prompt
respiratory or metabolic acidosis with compensatory hyperventilation, seizures, coma, and acute
hypotensive crisis. In an acute overdose, symptoms of renal failure (oliguric, with proteinuria and
hematuria), liver injury (hepatomegaly and jaundice), bone marrow depression, and ulceration (and
perforation) of the GI tract may develop. Other symptoms reported in humans include: nausea,
vomiting, abdominal pain, diaphoresis, neurologic and psychiatric symptoms, edema, hypertension,
respiratory depression, and cyanosis.
Standard overdose procedures should be followed (empty gut following oral ingestion, etc.).
Supportive treatment should be instituted as necessary and intravenous diazepam used to help
control seizures. Monitor fluid therapy carefully, as phenylbutazone may cause fluid retention.
Drug Interactions - Both phenylbutazone and the active metabolite oxyphenbutazone are highly
bound to plasma proteins and may displace other highly bound drugs. This mechanism may affect
serum levels and duration of actions of phentoin, valproic acid, oral anticoagulants, other
antiinflammatory agents, sulfonamides, and the sulfonylurea antidiabetic agents.
Phenylbutazone and oxyphenbutazone can induce hepatic microsomal enzymes and increase the
metabolism of drugs affected by this system (e.g., digitoxin & phenytoin). Conversely, other
microsomal enzyme inducers (e.g., barbiturates, promethazine, rifampin, corticosteroids, or
chlorpheniramine, diphenhydramine) may decrease the plasma half-life of phenylbutazone.
Phenylbutazone may increase the plasma half-life of penicillin G or lithium. Phenylbutazone
administered concurrently with hepatotoxic drugs may increase the chances of hepatotoxicity
developing.
Phenylbutazone may antagonize the increased renal blood flow effects caused by furosemide.
Concurrent use with other NSAIDs may increase the potential for adverse reactions developing,
however many clinicians routinely use phenylbutazone concomitantly with flunixin in horses.
Laboratory Test Interference - Phenylbutazone and oxyphenbutazone may interfere with thyroid
function tests by competing with thyroxine at protein binding sites or by inhibiting thyroid
iodine uptake.
Doses -
Dogs:
a) 14 mg/kg PO tid initially (maximum of 800 mg/day regardless of weight), titrate dose to
lowest effective dose (Package Insert; Butazolidin¨ - Coopers)
b) For analgesia/phlebitis: 3-5 mg/kg PO tid; for analgesia/spinal disorders: 8-10 mg/kg
PO tid (max. 800 mg/day); for antiinflammation/arthritis: 13 mg/kg PO tid for 48 hrs,
then taper dose to lowest effective dose (max. of 800 mg/day). (Morgan 1988)
Cattle:
a) 4 mg/kg IV or orally q24h (Koritz 1986)
b) 4 - 8 mg/kg PO or 2 - 5 mg/kg IV (Howard 1986)
c) 10 - 20 mg/kg PO, then 2.5 - 5.0 mg/kg q24h or 10 mg/kg every 48 hours PO (Jenkins
1987)
Horses:
a) 4.4 - 8.8 mg/kg q24hrs PO or 3-6 mg/kg q12h IV (Do not exceed 8.8 mg/kg/day
(Jenkins 1987)
b) 1 - 2 grams IV per 454 kg (1000 lb.) horse. Injection should be made slowly and with
care. Limit IV administration to no more than 5 successive days of therapy. Follow with
oral forms if necessary; or 2 - 4 grams PO per 454kg (1000 lb.) horse. Do not exceed 4
grams/day. Use high end of dosage range initially, then titrate to lowest effective dose.
(Package Insert; Butazolidin¨ - Coopers)
c) 4.4 mg/kg PO twice on the first day, then 2.2 mg/kg PO bid for 4 days, then 2.2 mg/kg
PO once daily or every other day. (Taylor et al. 1983)
Swine:
a) 4 mg/kg IV or orally q24h (Koritz 1986)
b) 4 - 8 mg/kg PO or 2 - 5 mg/kg IV (Howard 1986)
Monitoring Parameters - 1) Analgesic/anti-inflammatory/antipyrexic effect 2) Regular complete
blood counts with chronic therapy (especially in dogs). The manufacturer recommends weekly
CBCÕs early in therapy, and biweekly with chronic therapy 3) Urinalysis &/or renal function
parameters (serum creatinine/BUN) with chronic therapy 4) Plasma protein determinations,
especially in ponies, foals, and debilitated animals.Client
Information/FDA Approval Status - Do not administer injectable
preparation IM or SQ.
Approved for use in dogs and horses not intended for food. While phenylbutazone is not approved
for use in cattle, it is used. A general guideline for meat withdrawal times are: one dose=30
days, 2 doses=35 days, and 3 doses=40 days. Phenylbutazone is a veterinary prescription drug.
Dosage Forms/Preparations (Veterinary) -
Phenylbutazone Tablets 100 mg, 400 mg, 1 gram tablets; 2 gram boluses, 4 gram boluses ;
Butazolidin¨ (Schering); also available generically
Phenylbutazone Paste Oral syringes containing 6 grams or 12 grams/syringe; Butazolidin¨
Paste (Schering); Phenylzone¨ Paste (Luitpold)
Phenylbutazone Oral Gel: Each 30 grams of gel contains 4 grams phenylbutazone, 30 grams (of
gel) per syringe; Butatron¨ (Rhone Merieux)
Phenylbutazone Micro-encapsulated powder; Equipalazone¨ (Steri-Vet); 1 gm packets, 60Õs
Phenylbutazone Injection 200 mg/ml; 100 ml vials; Butazolidin¨ (Schering); generic








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موضوع كامل عن الphenyl butazone
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