Indomethacin

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DRUGS
Indomethacin

Indomethacin is a nonsteroidal anti-inflammatory drug (NSAID). Indomethacin works by reducing hormones that cause inflammation and pain in the body. It is used to treat moderate to severe osteoarthritis, rheumatoid arthritis, gouty arthritis, or ankylosing spondylitis. It is also used to treat shoulder pain caused by bursitis or tendinitis.

Introduction

Indomethacin is a nonsteroidal anti-inflammatory drug (NSAID). Indomethacin works by reducing hormones that cause inflammation and pain in the body. It is used to treat moderate to severe osteoarthritis, rheumatoid arthritis, gouty arthritis, or ankylosing spondylitis. It is also used to treat shoulder pain caused by bursitis or tendinitis.

Pharmacological Class: NSAID 

Indications

  • Rheumatoid arthritis
  • Osteoarthritis
  • Ankylosing spondylitis
  • Acute musculoskeletal disorders
  • Degenerative joint disease of the hip
  • low-back pain
  • Acute gouty arthritis.

Pharamcological Action

Indomethacin is a prostaglandin G/H synthase (also known as cyclooxygenase or COX) inhibitor that acts on both prostaglandin G/H synthase 1 and 2 (COX-1 and -2). Prostaglandin G/H synthase catalyzes the conversion of arachidonic acid to a number of prostaglandins involved in fever, pain, swelling, inflammation, and platelet aggregation. Indomethacin antagonizes COX by binding to the upper portion of the active site, preventing its substrate, arachidonic acid, from entering the active site. 

Dosage

Adult dose: 50 to 200 mg orally in divided doses with food

Pediatric dose: 1 mg/kg orally with 8 hour frequency

Note: Drug should not be given to pediatrics, pregnant mothers, patients suffering from liver malfunction, and neonates.

Pharmacokinetics

Oral absorption of Indomethacin is found to be 50% ±50. Volume of distribution is found to be 1 l/kg and plasma protein binding is 90-99%. Presystemic metabolism is noted to be 45.5% ±4.5 and metabolism is reported hepatic (extensive). Renal Excretion accounts for 60% and plasma half life is 1-16 hr.

Contraindications

  • Contraindicated in patients with history of peptic ulcer or active peptic ulcer.
  • A recurrent history of gastro-intestinal lesions
  • Patients who have nasal polyps associated with angioneurotic oedema
  • Patients who have experienced acute asthmatic attacks

Drug Interactions

  • Indomethacin bind reversibly at the active site of platelet cyclogenase and thus competitively inhibit this enzyme but because this binding is reversible so it cause temporary rather than sustained depression of thromboxane formation and thus antagonize the anti-platelet and cardio protective effect of low-dose aspirin
  • Indomethacin alters the antihypertensive effects of atenolol by inhibiting synthesis of renal prostaglandins results in unopposed pressor activity producing hypertension
  • Indomethacin may diminish the antihypertensive effect of captopril
  • Diminishes the diuretic effect of furosemide

Side effects

Common (affecting between 1 in10 to 1 in 100)

  • Upset stomach
  • Nausea & vomiting
  • Diarrhea
  • Constipation
  • Headache
  • Dizziness
  • Drowsiness
  • Ringing in your ears.

Uncommon (affecting 1 in 100 to 1 in 1000)

  • Pale skin
  • Fast heartbeat
  • Unusual bleeding or bruising
  • Back pain
  • Blurred vision or other problems with sight
  • Rash
  • Unexplained weight gain

Very rare (affecting less than 1 in 10,000)

  • Difficulty breathing or swallowing
  • Yellowing of the skin or eyes
  • Difficult or painful urination
  • Flu like symptoms

Precautions

  • Should be used with caution in patients with intrinsic coagulation defects and those on anticoagulant therapy.
  • Should be used with caution in patients with compromised cardiac function, hypertension other condition predisposing to fluid retention.
  • Should be used with extra care in the presence of existing controlled infection
  • The drug should not be prescribed in the children less than 14 years unless possible toxicity and lack of benefit from other drug justifies the risk.

Clinic Evidence

  • Twenty patients with definite or classical rheumatoid arthritis entered and completed a sequential study of placebo for 1 week, oral indomethacin 25 mg 3 times a day for 3 weeks, and oral indomethacin 25 mg 3 times a day plus 100 mg indomethacin suppository at night for 3 weeks. Twelve of the patients had previously been classified as responders and eight as nonresponders to indomethacin by an independent assessor. At the end of each period patient were assessed by a blind observer for duration of morning stiffness, pain score, digital joint size, grip strength, articular index, analgesic tablet usage, and the patient's own overall global assessment and comparative global assessment. In 8 of the 9 tests used responders improved on indomethacin in comparison with placebo, while nonresponders did not improve.

References

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