Phenylbutazone

Phenylbutazone is a NSAID ("non-steroidal anti-inflammatory drugs") that has anti-inflammatory, antipyretic and analgesic effects. It is particularly effective in the treatment of ankylosing spondylitis. It is also used in rheumatoid arthritis, gout attacks and Reiter's syndrome when other better-tolerated drugs do not work adequately. In veterinary medicine, phenylbutazone is used to relieve pain and reduce fever in horses and dogs.

Phenylbutazone was first manufactured and patented by Geigy (now Novartis) in 1951.

Pharmacodynamics

Phenylbutazone is a synthetic pyrazolone derivative. The analgesic effect results from inhibition of the production of prostaglandin H and prostacyclin zu. Prostaglandins act on a variety of cells, such as vascular smooth muscle cells, platelets, and nerve cells in the spinal cord that cause pain sensation. Prostacyclin causes vasoconstriction and inhibits platelet aggregation. Phenylbutazone acts by binding and inhibiting prostaglandin H synthase and prostacyclin synthase. The decreased production of prostaglandin then results in less inflammation of surrounding tissues.

Pharmacokinetics

Phenylbutazone is almost completely absorbed in the small intestine and maximum plasma levels are reached after approximately 2 hours. The substance is present more than 95% bound to plasma proteins. The substance is metabolized in the liver and 70% is excreted by the kidney and about 30% by the biliary tract.

Interactions

Phenylbutazone is a CYP3A4 inducer and therefore may interact with a large number of drugs that are metabolized via CYP3A4. Phenylbutazone may therefore affect the blood levels and duration of action of the following drugs:

• Phenytoin
• Valproic acid
• Sulfonamides
• Sulfonylurea antidiabetics
• Barbiturates
• Promethazine
• Rifampicin
• Chlorpheniramine
• Diphenhydramine
• penicillin G

In addition, concomitant use with other anti-inflammatory drugs, such as corticosteroids and other NSAIDs, may promote increased formation of gastric ulcers and increase the risk of bleeding. Combination with anticoagulant drugs, especially coumarin derivatives, also increases the risk of bleeding.

Side effects

The following side effects may occur after taking phenylbutazone:

• Edema
• Agranulocytosis
• Increased ulcer formation
• Bleeding
• Anemia
• Renal damage

Phenylbutazone overdose can lead to renal failure, liver damage, bone marrow suppression, and gastric ulceration or perforation. Early signs of toxicity include loss of appetite and depression.

Contraindications

Phenylbutazone may have an adverse effect on the embryo and may also pass into breast milk. Therefore, use during pregnancy and lactation is not recommended.