Indometacin

Indomethacin (USAN) or indometacin (INN) is a non-steroidal anti-inflammatory drug commonly used to reduce fever, pain, stiffness, and swelling. It works by inhibiting the production of prostaglandins, molecules known to cause these symptoms. It is marketed under many trade names, including Indocin, Indocid, Indochron E-R, and Indocin-SR. more...

Chemical properties

Indomethacin is a methylated indole derivative and a member of the arylalkanoic acid class of NSAIDs.

Indications

Clinical indications for indomethacin include:

• ankylosing spondylitis
• rheumatoid arthritis
• arthritic gout
• osteoarthritis
• juvenile arthritis
• psoriatic arthritis
• Reiter's syndrome
• Paget's disease of bone
• Bartter syndrome
• pseudogout
• dysmenorrhea (menstrual cramps)
• pericarditis
• bursitis
• tendinitis
• nephrogenic diabetes insipidus (prostaglandin inhibits vasopressin's action in the kidney)
• fever and pain associated with malignant diseases (tumors, bony metastasis, lymphogranulomatosis)

Indomethacin has also been used clinically to delay premature labor, reduce amniotic fluid in polyhydramnios, and to treat patent ductus arteriosus.

Indomethacin is a potent drug with many serious side effects and should not be considered an analgesic for minor aches and pains or fever. The drug is more potent than Aspirin, but the usually tolerated doses of Indomethacin do not allow a superior efficiency compared to Aspirin. In mild to moderate pain a usual oral dose of Indomethacin proved as efficient as 600mg Aspirin.

Contraindications

• acutely existing Ulcus ventriculi and/or duodeni, or history of Ulcus
• allergy against Indomethacin, Aspirin, or other NSAIDs
• patients with nasal polyps reacting with an angioedema to other NSAIDS
• children under 2 years of age
• severe preexisting renal and liver damage
• caution : preexisting bone marrow damage (frequent blood cell counts indicated)
• caution : bleeding tendencies of unknown origin (Indomethacin inhibits platelet aggregation)
• caution : Morbus Parkinson, epilepsy, psychic disorders (Indomethacin may worsen these conditions)

Mechanism of action

Indomethacin is a nonselective inhibitor of cyclooxygenase (COX) 1 and 2, enzymes that participate in prostaglandin synthesis from arachidonic acid. Prostaglandins are hormone-like molecules normally found in the body, where they have a wide variety of effects, some of which lead to pain, fever, and inflammation.

Prostaglandins also cause uterine contractions in pregnant women. Indomethacin is an effective tocolytic agent, able to delay premature labor by reducing uterine contractions through inhibition of PG synthesis in the uterus and possibly through calcium channel blockade.

Indomethacin has 2 additional modes of actions with clinical importance:

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