Diclofenac

Class

    • Antipyretic/analgesic NSAID

Indications

    • pain

    • dysmenorrhea

    • ocular inflammation

    • osteoarthritis

    • rheumatoid arthritis

    • ankylosing spondylitis

    • actinic keratosis

Administration/Absorption

    • Completely absorbed from the gastrointestinal tract

    • Topical cream

Dosage

Distribution

Mechanism

    • 2-(2,6-dichloranilino) phenylacetic acid

    • The most potent NSAID on a broad basis

    • COX-1 and COX-2 inhibition

      • => peripheral inhibition of prostaglandin synthesis

      • Approximately 10-fold for the COX2-isoenzyme

    • Somewhat lower incidence of gastrointestinal complaints than noted with indomethacin and aspirin

    • Inhibition of leukocyte migration

    • Antipyretic effects may be due to action on the hypothalamus, resulting in peripheral dilation, increased cutaneous blood flow, and subsequent heat dissipation

    • There is some evidence that diclofenac inhibits the lipoxygenase pathways thus reducing formation of the leukotrienes

    • There is also speculation that diclofenac may inhibit phospholipase A2

Excretion

    • The action of one single dose is much longer (6 to 8 hours) than the very short half-life that the drug indicates

Side effects

Interactions

Contraindications

    • Hypersensitivity against diclofenac

    • History of allergic reactions (bronchospasm, shock, rhinitis, urticaria) following the use of Aspirin or another NSAID

  • Third-trimester pregnancy

    • Active stomach and/or duodenal ulceration or gastrointestinal bleeding

    • Inflammative intestinal disorders such as Crohn's disease or ulcerative colitis

    • Severe insufficiency of the heart (NYHA III/IV)

    • Recently, a warning has been issued by FDA not to use to treat patients recovering from heart surgery

    • Severe liver insufficiency (Child-Pugh Class C)

    • Severe renal insufficiency (creatinine clearance <30 ml/min)

    • Caution in patients with preexisting hepatic porphyria, as diclofenac may trigger attacks

    • Caution in patients with severe, active bleeding such as cerebral hemorrhage

    • NSAIDs in general should be avoided during dengue fever.