Equipalazone

Indications

• Rheumatoid arthritis
• Osteoarthritis
• Ankylosing spondylitis
• Gout
• Acute musculoskeletal pain
• Postoperative pain

Dosage

Children: For children, the dosage must be determined on an individual basis and should refer to the BNF for Children for specific guidance.

Adults: The usual adult dose is 200 to 400 mg daily, divided into 1 or 2 doses. In acute conditions, higher doses may be used initially, followed by a gradual reduction.

Mechanism of action

Phenylbutazone binds to and inactivates prostaglandin H synthase and prostacyclin synthase through peroxide-mediated deactivation. This reduces the production of prostaglandins, leading to decreased inflammation in surrounding tissues. By inhibiting cyclooxygenase, it blocks the conversion of arachidonic acid into various prostaglandins, which are mediators of pain and inflammation.

Pharmacodynamics

As a pyrazolone derivative, phenylbutazone exhibits its therapeutic effects primarily through its anti-inflammatory properties, which are related to its ability to decrease the production of prostaglandins. This action affects various cells, including vascular smooth muscle cells, platelets, and spinal neurons, ultimately resulting in reduced pain and inflammation.

Pharmacokinetics

Phenylbutazone is well absorbed from the gastrointestinal tract, with peak plasma concentrations typically reached within 1 to 2 hours after oral administration. It has a long half-life, allowing for once-daily dosing in some cases. The drug is extensively protein-bound, primarily to albumin, and is metabolized in the liver. Renal excretion is the main route of elimination, with both unchanged drug and metabolites being excreted in the urine.

Contra-indications

• Hypersensitivity to phenylbutazone or other pyrazolone derivatives
• Active peptic ulcer disease
• Severe hepatic or renal impairment
• History of gastrointestinal bleeding
• Severe cardiovascular disease

Adverse effects

• Gastrointestinal irritation
• Nausea
• Vomiting
• Diarrhea
• Headache
• Dizziness
• Skin rash
• Agranulocytosis
• Hepatitis
• Renal impairment

Interactions

• Warfarin: may enhance anticoagulant effects
• Methotrexate: may increase toxicity
• Other NSAIDs: increased risk of adverse effects
• Diuretics: may reduce effectiveness
• Antihypertensives: may reduce effectiveness

Precautions

• Use with caution in patients with a history of gastrointestinal disease
• Monitor liver and renal function during prolonged therapy
• Use with caution in elderly patients

Pregnancy

Use is generally not recommended due to potential risks to the fetus, especially during the third trimester.

Breast-feeding

Caution is advised as phenylbutazone may be excreted in breast milk.

Storage

Store in a cool, dry place away from light. Keep out of reach of children.

Formulations

• Tablets
• Injectable formulations

Mechanism of action

Phenylbutazone binds to and inactivates prostaglandin H synthase and prostacyclin synthase through peroxide (H2O2) mediated deactivation. The reduced production of prostaglandin leads to reduced inflammation of the surrounding tissues. The drug exhibits anti-inflammatory, analgesic, antipyretic, and mild uricosuric activity. The exact mechanisms have not been clearly established, but many of the actions appear to be associated principally with the inhibition of prostaglandin synthesis. Many nonsteriodal anti- inflammatory agents inhibit the synthesis of prostaglandins in body tissues by inhibiting cyclooxygenase, an enzyme that catalyzes the formation of prostaglandin precursors (endoperoxides) from arachidonic acid. Nonsteroidal anti-inflammatory drugs probably act by inhibiting prostaglandin synthesis. Prostaglandins prostaglandins are believed to cause vasodilaton, increased vascular permeability, and increased sensitivity of nerve endings to other inflammatory mediators. By reversibly inhibiting the enzyme cyclooxygenase, nonsteroidal anti-inflammatory drugs block the conversion of the arachidonic acid found in cell membrane phospholipids into varius prostaglandins (E2,F2,D2, thromboxane A2). Since prostaglandins appear to maintain the gastric mucosal barrier nonsteroidal anti-inflammatory drugs inhibition of prostaglandins synthesis may be the cause of the gastritis, peptic ulcerations, and gastrointestinal bleeding observed with nonsteroidal anti-inflammatory drugs. Nonsteroidal anti-inflammatory drugs cause sodium retention, especially in patients with underlying sodium-retaining states such as congestive heart failure. Although the mechanism is not entirely clear, the inhibition of prostaglandins synthesis plays a leading role. These compounds redistribute renal blood flow away from the superficial cortical glomeruli to the juxtamedullary glomeruli, which have a greater capacity to absorb sodium. Stress intensifies the effect of prostaglandins. /Nonsteroidal anti-inflammatory drugs/ Phenylbutazone exists in solution in three forms--a diketo, an enol, and a mesomeric anion form. In solution, it exists primarily in the diketo form, and conversion between the forms is slow. These transformations probably contribute to its chemical instability and the ability of the cyclooxygenase system to generate the 4-hydroxphenylbutazone metabolite by a peroxide-dependent cooxygenation reaction. This reaction has been shown to produce reactive intermediates capable of inactivating prostacyclin synthase and prostaglandin H synthase, which may account for phenylbutazone's anti-inflammatory activity. Mechanism of anti-inflammatory effects of phenylbutazone is not known. ... Inhibits biosynthesis of prostaglandins, uncouples oxidative phosphorylation, and inhibits ATP-dependent biosynthesis of mucopolysaccharide sulfates in cartilage.

Pharmacodynamics

Phenylbutazone is a synthetic, pyrazolone derivative. It is a nonhormonal anti-inflammatory, antipyretic compound useful in the management of inflammatory conditions. The apparent analgesic effect is probably related mainly to the compound's anti-inflammatory properties and arise from its ability to reduce production of prostaglandin H and prostacyclin. Prostaglandins act on a variety of cells such as vascular smooth muscle cells causing constriction or dilation, on platelets causing aggregation or disaggregation and on spinal neurons causing pain. Prostacylcin causes vascular constriction platelet disaggregation