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Phenylbutazone
Phenylbutazone 629
Stability and Storage Store in a tightly sealed container, protected from light, and at room temperature.
Small Animal Dosage Dogs and Cats • 0.02-0.1 mg/kg IV.
Large Animal Dosage • No doses have been reported for large animals.
Regulatory Information Withdrawal times are not established for animals that produce food. For extralabel use withdrawal interval estimates, contact FARAD at 1-888-USFARAD (1-888-873-2723). RCI Classification: 3
Phenylbutazone fen-ill-byoo’tah-zone
Trade and other names: Butazolidin, PBZ, and generic brands Functional classification: Nonsteroidal anti-inflammatory drug
Pharmacology and Mechanism of Action Phenylbutazone and other NSAIDs produce analgesic and anti-inflammatory effects by inhibiting the synthesis of prostaglandins. The enzyme inhibited by NSAIDs is the cyclooxygenase (COX) enzyme. The COX enzyme exists in two isoforms: COX-1 and COX-2. COX-1 is primarily responsible for synthesis of prostaglandins important for maintaining a healthy gastrointestinal tract, renal function, platelet function, and other normal functions. COX-2 is induced and responsible for synthesizing prostaglandins that are important mediators of pain, inflammation, and fever. However, it is known that there is some crossover of COX-1 and COX-2 effects in some situations, and COX-2 activity is important for some biological effects. Phenylbutazone, using in vitro assays, is a nonselective inhibitor of COX-1 and COX-2. It has a halflife of 36-65 days in cattle, 5 hours in horses, and 4-6 hours in dogs.
Indications and Clinical Uses Many equine experts believe that phenylbutazone is the most cost-effective treatment for osteoarthritis in horses. The major use of phenylbutazone is in horses for musculoskeletal pain and inflammation, arthritis, soft tissue injury, and racing injuries. It is approved in both dogs and horses. The duration of action in horses after a single administration is approximately 24 hours. Phenylbutazone is approved for use in dogs (and cats in Europe); however, the use in small animals is not common because of the availability of other drugs.
Precautionary Information Adverse Reactions and Side Effects Although adverse effects have been documented in horses, after 30 years of experience, most equine clinicians have observed good safety with phenylbutazone. Earlier studies that demonstrated common adverse effects may have been exaggerated because the studies were performed in ponies, which is a breed more sensitive than horses. Likewise, draft horses appear to be more sensitive to adverse effects.
630 Phenylbutazone Among the adverse effects in horses are gastrointestinal ulcers. Gastric ulcers are more likely as the dose increases and in animals undergoing extensive training. Horses may also develop right dorsal colitis and hypoproteinemia, especially at high doses. Phenylbutazone has been associated with kidney injury. In horses that are dehydrated or have renal compromise, phenylbutazone can cause ischemia and renal papillary necrosis. In experimental horses, phenylbutazone (4.4 mg/kg q12h for 14 days) decreased proteoglycan synthesis in articular cartilage. However, this effect on articular cartilage with clinical use has not been a documented problem. Phenylbutazone is rarely used in people because it has caused bone marrow depression, including aplastic anemia. This effect also has been observed in animals. Phenylbutazone is generally well tolerated in dogs, but there are no data for cats. In these animals, adverse effects possible are gastrointestinal toxicity such as gastritis and gastric ulcers. Contraindications and Precautions Do not administer injectable formulation intramuscularly. Do not administer to animals prone to gastrointestinal ulcers or to animals with kidney disease that may become dehydrated. Do not administer with other ulcerogenic drugs, such as corticosteroids. Drug Interactions The use with other NSAIDs or with corticosteroids should be done cautiously because of the risk of gastrointestinal injury. Corticosteroids have been shown to exacerbate the gastrointestinal adverse effects. Phenylbutazone has been used in some horses in combination with flunixin meglumine (NSAID “stacking”), but this combination may increase risk of hypoalbuminemia and decreased total serum protein. Phenylbutazone will interfere with the action of furosemide in horses. Some NSAIDs also may interfere with the action of angiotensin-converting enzyme (ACE) inhibitors.
Instructions for Use Doses are based primarily on manufacturer’s recommendations and clinical experience. Although a range of 4.4-8.8 mg/kg per day has been administered to horses, studies have not shown an advantage for the higher dose, and the higher dose of 8.8 mg/kg per day is more likely to cause gastrointestinal injury, hypoalbuminemia, and neutropenia. Generally, a safe starting dose in horses is 4.4 mg/kg every 12 hours IV or PO for 2-3 days. Then the dose should be tapered to 2.2-3.3 mg/kg q12h PO. Combining other NSAIDs with phenylbutazone, such as flunixin (referred to as “stacking”), may improve response when treating lameness and other musculoskeletal problems when compared to phenylbutazone alone. However, this practice must be weighed against an increased risk of gastrointestinal injury.
Patient Monitoring and Laboratory Tests Monitor CBC for signs of bone marrow toxicity with chronic use.
Formulations • Phenylbutazone is available in 100-mg, 200-mg, 400-mg and 1-g tablets (bolus); oral paste for horses; and 200-mg/mL (20%) solution for injection.
Stability and Storage Store in a tightly sealed container, protected from light, and at room temperature. Phenylbutazone is not water soluble. It should not be compounded in aqueous vehicles.
Phenylephrine Hydrochloride 631
Small Animal Dosage Dogs • 15-22 mg/kg q8-12h (44 mg/kg/day; 800 mg/dog maximum) PO or IV. Cats • 6-8 mg/kg q12h IV or PO.
Large Animal Dosage Horses • 4.4-8.8 mg/kg/day (generally 2 g to 4 g per horse) PO. Typically, a dose of 4.4 mg/kg is administered every 12 hours for the first 2-3 days, followed by a tapering dose to 2.2 mg/kg q12h. It is not recommended to use the highest dose for more than 48-96 hours. • Injection: 2.2-4.4 mg/kg/day for 48-96 hours. Give injections intravenously only, as IM injections will cause tissue irritation. Cattle • 17-25 mg/kg loading dose, then 2.5-5 mg/kg q24h or 10-14 mg/kg q48h PO or IV. (See regulatory restrictions in cattle.) Pigs • 4 mg/kg q24h IV.
Regulatory Information Phenylbutazone is prohibited from use in female dairy cattle younger than 20 months of age. Other withdrawal times have not been established for animals intended for food. However, recommended withdrawal times are 15 days in swine, 40-50 days for slaughter in cattle (oral or IV), and extended to 55 days in cattle if administered intramuscularly. Residue information for horses: Although it is possible that phenylbutazone residues can occur in horses being slaughtered for food—in jurisdictions where this is allowed—the risk to human health is very low. Some experts do not regard this as a public health issue.
Phenylephrine Hydrochloride fen-ill-ef’rin hye-droe-klor’ide
Trade and other names: Neo-Synephrine Functional classification: Vasopressor
Pharmacology and Mechanism of Action Alpha1-adreneric receptor agonist. Phenylephrine will stimulate alpha1-receptors and cause smooth muscle contraction, primarily in vascular smooth muscle, to cause vasoconstriction. It may be applied topically (e.g., mucous membranes) to constrict superficial blood vessels.
Indications and Clinical Uses Phenylephrine is used primarily in critical care patients or during anesthesia to increase peripheral resistance and increase blood pressure. Phenylephrine is also used commonly as topical vasoconstrictor (as in nasal decongestants or for ophthalmic use). It has been administered to horses with nephrosplenic entrapment because the vasoconstriction it produces may produce splenic contraction. Although the incidence of
Stability and Storage Store in a tightly sealed container, protected from light, and at room temperature.
Small Animal Dosage Dogs and Cats • 0.02-0.1 mg/kg IV.
Large Animal Dosage • No doses have been reported for large animals.
Regulatory Information Withdrawal times are not established for animals that produce food. For extralabel use withdrawal interval estimates, contact FARAD at 1-888-USFARAD (1-888-873-2723). RCI Classification: 3
Phenylbutazone fen-ill-byoo’tah-zone
Trade and other names: Butazolidin, PBZ, and generic brands Functional classification: Nonsteroidal anti-inflammatory drug
Pharmacology and Mechanism of Action Phenylbutazone and other NSAIDs produce analgesic and anti-inflammatory effects by inhibiting the synthesis of prostaglandins. The enzyme inhibited by NSAIDs is the cyclooxygenase (COX) enzyme. The COX enzyme exists in two isoforms: COX-1 and COX-2. COX-1 is primarily responsible for synthesis of prostaglandins important for maintaining a healthy gastrointestinal tract, renal function, platelet function, and other normal functions. COX-2 is induced and responsible for synthesizing prostaglandins that are important mediators of pain, inflammation, and fever. However, it is known that there is some crossover of COX-1 and COX-2 effects in some situations, and COX-2 activity is important for some biological effects. Phenylbutazone, using in vitro assays, is a nonselective inhibitor of COX-1 and COX-2. It has a halflife of 36-65 days in cattle, 5 hours in horses, and 4-6 hours in dogs.
Indications and Clinical Uses Many equine experts believe that phenylbutazone is the most cost-effective treatment for osteoarthritis in horses. The major use of phenylbutazone is in horses for musculoskeletal pain and inflammation, arthritis, soft tissue injury, and racing injuries. It is approved in both dogs and horses. The duration of action in horses after a single administration is approximately 24 hours. Phenylbutazone is approved for use in dogs (and cats in Europe); however, the use in small animals is not common because of the availability of other drugs.
Precautionary Information Adverse Reactions and Side Effects Although adverse effects have been documented in horses, after 30 years of experience, most equine clinicians have observed good safety with phenylbutazone. Earlier studies that demonstrated common adverse effects may have been exaggerated because the studies were performed in ponies, which is a breed more sensitive than horses. Likewise, draft horses appear to be more sensitive to adverse effects.
630 Phenylbutazone Among the adverse effects in horses are gastrointestinal ulcers. Gastric ulcers are more likely as the dose increases and in animals undergoing extensive training. Horses may also develop right dorsal colitis and hypoproteinemia, especially at high doses. Phenylbutazone has been associated with kidney injury. In horses that are dehydrated or have renal compromise, phenylbutazone can cause ischemia and renal papillary necrosis. In experimental horses, phenylbutazone (4.4 mg/kg q12h for 14 days) decreased proteoglycan synthesis in articular cartilage. However, this effect on articular cartilage with clinical use has not been a documented problem. Phenylbutazone is rarely used in people because it has caused bone marrow depression, including aplastic anemia. This effect also has been observed in animals. Phenylbutazone is generally well tolerated in dogs, but there are no data for cats. In these animals, adverse effects possible are gastrointestinal toxicity such as gastritis and gastric ulcers. Contraindications and Precautions Do not administer injectable formulation intramuscularly. Do not administer to animals prone to gastrointestinal ulcers or to animals with kidney disease that may become dehydrated. Do not administer with other ulcerogenic drugs, such as corticosteroids. Drug Interactions The use with other NSAIDs or with corticosteroids should be done cautiously because of the risk of gastrointestinal injury. Corticosteroids have been shown to exacerbate the gastrointestinal adverse effects. Phenylbutazone has been used in some horses in combination with flunixin meglumine (NSAID “stacking”), but this combination may increase risk of hypoalbuminemia and decreased total serum protein. Phenylbutazone will interfere with the action of furosemide in horses. Some NSAIDs also may interfere with the action of angiotensin-converting enzyme (ACE) inhibitors.
Instructions for Use Doses are based primarily on manufacturer’s recommendations and clinical experience. Although a range of 4.4-8.8 mg/kg per day has been administered to horses, studies have not shown an advantage for the higher dose, and the higher dose of 8.8 mg/kg per day is more likely to cause gastrointestinal injury, hypoalbuminemia, and neutropenia. Generally, a safe starting dose in horses is 4.4 mg/kg every 12 hours IV or PO for 2-3 days. Then the dose should be tapered to 2.2-3.3 mg/kg q12h PO. Combining other NSAIDs with phenylbutazone, such as flunixin (referred to as “stacking”), may improve response when treating lameness and other musculoskeletal problems when compared to phenylbutazone alone. However, this practice must be weighed against an increased risk of gastrointestinal injury.
Patient Monitoring and Laboratory Tests Monitor CBC for signs of bone marrow toxicity with chronic use.
Formulations • Phenylbutazone is available in 100-mg, 200-mg, 400-mg and 1-g tablets (bolus); oral paste for horses; and 200-mg/mL (20%) solution for injection.
Stability and Storage Store in a tightly sealed container, protected from light, and at room temperature. Phenylbutazone is not water soluble. It should not be compounded in aqueous vehicles.
Phenylephrine Hydrochloride 631
Small Animal Dosage Dogs • 15-22 mg/kg q8-12h (44 mg/kg/day; 800 mg/dog maximum) PO or IV. Cats • 6-8 mg/kg q12h IV or PO.
Large Animal Dosage Horses • 4.4-8.8 mg/kg/day (generally 2 g to 4 g per horse) PO. Typically, a dose of 4.4 mg/kg is administered every 12 hours for the first 2-3 days, followed by a tapering dose to 2.2 mg/kg q12h. It is not recommended to use the highest dose for more than 48-96 hours. • Injection: 2.2-4.4 mg/kg/day for 48-96 hours. Give injections intravenously only, as IM injections will cause tissue irritation. Cattle • 17-25 mg/kg loading dose, then 2.5-5 mg/kg q24h or 10-14 mg/kg q48h PO or IV. (See regulatory restrictions in cattle.) Pigs • 4 mg/kg q24h IV.
Regulatory Information Phenylbutazone is prohibited from use in female dairy cattle younger than 20 months of age. Other withdrawal times have not been established for animals intended for food. However, recommended withdrawal times are 15 days in swine, 40-50 days for slaughter in cattle (oral or IV), and extended to 55 days in cattle if administered intramuscularly. Residue information for horses: Although it is possible that phenylbutazone residues can occur in horses being slaughtered for food—in jurisdictions where this is allowed—the risk to human health is very low. Some experts do not regard this as a public health issue.
Phenylephrine Hydrochloride fen-ill-ef’rin hye-droe-klor’ide
Trade and other names: Neo-Synephrine Functional classification: Vasopressor
Pharmacology and Mechanism of Action Alpha1-adreneric receptor agonist. Phenylephrine will stimulate alpha1-receptors and cause smooth muscle contraction, primarily in vascular smooth muscle, to cause vasoconstriction. It may be applied topically (e.g., mucous membranes) to constrict superficial blood vessels.
Indications and Clinical Uses Phenylephrine is used primarily in critical care patients or during anesthesia to increase peripheral resistance and increase blood pressure. Phenylephrine is also used commonly as topical vasoconstrictor (as in nasal decongestants or for ophthalmic use). It has been administered to horses with nephrosplenic entrapment because the vasoconstriction it produces may produce splenic contraction. Although the incidence of