What is Indomethacin (NSAIDs) & What is it Used For?|What are the Side Effects of Indomethacin?

Indomethacin is being prescribed as NSAIDS for treatment of inflammation and joint pain. Side effects like gastric ulcer and mucosal bleeding is more often seen following indomethacine treatment compared to most alternative second generation NSAIDs. Indomethacine is less frequently used because less side effects are observed with alternative NSAIDs. In most cases anti-ulcer medications like rhinitidine are prescribed at bed time if patient is given indomethacine treatment. The first batch of Indomethacin was manufactured in 1963. The drug was sold in 1965.

What is Indomethacin  (NSAIDs)?

How Does Indomethacin Work? : Mechanism of Action

Indomethacin is nonselective cyclooxygenase (COX) enzyme inhibitor and blocks COX 1 and 2 enzymes. Like all NSAIDs, indomethacin blocks conversion of Arachnoidic acid to prostaglandin and Thromboxane and Levuloglandin. Arachidonic acid and prostaglandins are found in almost all anatomical sites of human body. Prostaglandin protects gastric and intestinal mucosal membrane and lack of prostaglandin causes formation gastric and intestinal ulcer as well bleeding. Increase concentration of prostaglandin resets body temperature at higher level that results in fever. Prostaglandin secretion is increased when body soft tissue and bones are injured or infected. Prostaglandin initiates physiological defense known as inflammation to protect the surrounding normal tissue. NSAIDs like Indomethacin restricts the spread of inflammation into normal surrounding tissue, resets the temperature center to normal temperature and decreases pain by decrease secretion of prostaglandin.

Uses: Indomethacin is Used To Treat Following Diseases

  • Joint Pain and Arthritis- Joint pains caused by osteoarthritis, rheumatoid arthritis, ankylosing spondylitis and gout are treated with indomethacin. Indomethacin is also used to treat juvenile arthritis.
  • Soft Tissue Inflammation- Soft tissue pain caused by inflammation like tendinitis, ligamental inflammation, myalgia and muscle spasm are treated with indomethacin.
  • Nerve Pain- Nerve pain like radicular pain caused by pinch nerve, trigeminal neuralgia and pain caused by diabetic neuralgia are treated with indomethacine.
  • Headache- Headache caused by paroxysmal hemicranias, tension headache and exercise is treated with indomethacin.
  • Patent ductus arteriosus- Premature infant born with patent ductus arteriosus are treated with indomethacin to promote closure of ductus arteriosus.
  • Premature labor and menstrual pain- Indomethacine is used to delay premature labor as well as reduce amniotic fluid secretion in mother suffering with labor polyhydramnios. Prostaglandin causes contraction of uterine muscles during third trimester that results in normal or premature delivery of child. Indomethacin reduces prostaglandin secretion and prevents premature contraction of uterine muscles resulting in delay of premature labor as well as decrease in menstrual pain.
  • Headache- Migraine and tension headache are treated with indomethacin.
  • Kidney and Ureter Stone- Pain as well as inflammation caused by kidney and ureter stone.

Dosage of Indomethacin

Indomethacin dosage is restricted to 50 to 200 mg per day. In most cases symptoms are relieved with 50 to 100 mg dosage. Rarely dosage of 200 mg is used. The medication is prescribed for 10 to 15 days.

Duration of Action of Indomethacin

The peak concentration of Indomethacin is observed in 2 to 3 hours. Most of the drug is absorbed in 4 hours and over 90% medication is available, thus therapeutic dosage required is low. In most cases 50 mg of Indomethacin gives optimum pain relief and rapidly reduces inflammation.

Side Effects Caused by Indomethacin

  • Abdominal pain- Abdominal pain is caused by gastric or intestinal ulcer.
  • Bleeding disorder- Inhibition of cyclooxygenase enzyme decreases secretion of enzyme thromboxane A2. Lack of thromboxane A2 enzyme impairs function of platelet aggregation that results in systemic bleeding tendency because of prolonged bleeding time. Abrasion or minor trauma of skin or joint causes subcutaneous (bruises) or intraarticular bleeding. Similarly, mucosal ulcer also bleeds for prolonged period of time.
  • Vomiting- Indomethacin causes nausea and vomiting. The vomiting in few cases shows coffee color vomitus because of intestinal bleeding.
  • Diarrhea- Diarrhea is rare but may be associated with loose dark stool contains blood.
  • Central Nervous System- Dizziness and drowsiness are often seen if treatment is continued for prolong period. Numbness of extremities and Vertigo is rare but rarely observed in few cases.
  • Skin Rash- Allergies to indomethacin NSAIDs causes skin rash.
  • Bronchospasm- Retention of fluid and anaphylactic reaction to indomethacin causes edematous airway and bronchospasm secondary to spasm of bronchial smooth muscles. The condition often is life threatening and may need to visit ER in least possible time.
  • Hypertension- Retention of fluid and systemic vasoconstriction because of lack of prostaglandin causes hypertension in few cases.
  • Constipation- Constipation is observed in few cases because of hard stool as well as decrease intestinal contraction.
  • Tinnitus- Indomethacin and most NSAIDs causes reversible damage of outer hair cells as well as central auditory neurons. In addition, in few cases cochlear injuries causes hearing loss which in few cases become permanent.
  • Dizziness and drowsiness- Prolong intake of indomethacin in large dosage can cause symptoms like dizziness and drowsiness that may follow confusion, disorientation and restlessness.

Indomethacin is Avoided in Patient Suffering with Following Disease

  • Peptic ulcer
  • Nasal polyp
  • Liver diseases
  • Kidney disease- nephrotic syndrome and renal failure
  • Bruises because of bleeding tendency
  • Psychiatric diseases- symptoms of diseases like bipolar disorder or depression gets worst.
  • Epilepsy
  • Hypertension
  • Drug interactions- avoided if patient is taking other type of NSAIDs or lithium medication.

References

  1. Cyclooxygenase enzymes: regulation and function.

    Curr Pharm Des. 2004;10(6):577-88., Fitzpatrick FA1.

  2. Role of indomethacin in acute pain and inflammation management: a review of the literature.

    Postgrad Med. 2014 Jul;126(4):92-7, Nalamachu S1, Wortmann R.

  3. Nonsteroidal Anti-Inflammatory Drugs and Hypertension.

    J Clin Hypertens (Greenwich). 2000 Oct;2(5):319-323., Brook RD1, Kramer MB, Blaxall BC, Bisognano JD.

  4. Ototoxicity: mechanisms of cochlear impairment and its prevention.

    Curr Med Chem. 2011;18(31):4866-71., Tabuchi K1, Nishimura B, Nakamagoe M, Hayashi K, Nakayama M, Hara A.

  5. Acute poisoning due to non-steroidal anti-inflammatory drugs. Clinical features and management.

    Vale JA, Meredith TJ., Med Toxicol. 1986 Jan-Feb;1(1):12-31.

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