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Diclofenac
- indication:For the acute and chronic treatment of signs and symptoms of osteoarthritis and rheumatoid arthritis.
- pharmacologypharmacology:
- mechanism: The antiinflammatory effects of diclofenac are believed to be due to inhibition of both leukocyte migration and the enzyme cylooxygenase (COX-1 and COX-2), leading to the peripheral inhibition of prostaglandin synthesis. As prostaglandins sensitize pain receptors, inhibition of their synthesis is responsible for the analgesic effects of diclofenac. Antipyretic effects may be due to action on the hypothalamus, resulting in peripheral dilation, increased cutaneous blood flow, and subsequent heat dissipation.
- toxicity: Symptoms of overdose include loss of consciousness, increased intracranial pressure, and aspiration pneumonitis. LD<sub>50</sub>=390mg/kg (orally in mice)
- absorprion: Completely absorbed from the gastrointestinal tract.
- halflife: 2 hours
- roouteelimination: Diclofenac is eliminated through metabolism and subsequent urinary and biliary excretion of the glucuronide and the sulfate conjugates of the metabolites. Little or no free unchanged diclofenac is excreted in the urine. Approximately 65% of the dose is excreted in the urine and approximately 35% in the bile as conjugates of unchanged diclofenac plus metabolites.
- volumedistribution: * 1.3 L/kg
- clearance: * oral cl=622 mL/min [healthy] * renal cl <1 mL/min [healthy]