Indomethacin chemical structure
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Indocin

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...

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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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Inappropriate prescribing for older patients
From American Family Physician, 7/1/05 by Karl E. Miller

Less than 15 percent of the U.S. population is older than 65 years, yet this age group accounts for nearly one third of prescription drug use. Older patients also tend to have multiple chronic diseases, requiring them to take several drugs simultaneously. The risk of adverse events related to medication use increases among older patients because of age-related changes in metabolism and excretion of drugs. In 1991, criteria were published to determine the appropriateness of medications used by nursing home residents. These criteria were revised recently to include 28 medications or classes of medications considered inappropriate for use in older patients. Curtis and associates used these criteria to determine the extent of inappropriate outpatient prescribing for older patients.

The study design was a retrospective cohort analysis of outpatient prescription claims collected from the database of a large national pharmaceutical management company, which involved participants from all 50 states. Patients were included if they were 65 years or older at the start of the data collection period and had filed at least one prescription claim within the one-year study period. The authors limited their analysis to the 18 medications that the consensus panel recommended avoiding in older patients at any dosage or frequency. The main outcome measure was the number of patients taking one or more of the 18 medications. The secondary outcome measure was the number of patients taking two or more of the medications.

The data reviewed were from 1999 and identified 765,423 patients who met the inclusion criteria. Twenty-one percent (n = 162,370) filled a prescription for one or more of the medications. The most common prescription drugs that should be avoided in this age group include amitriptyline (Elavil) and doxepin (Sinequan; see the accompanying table). Of the patients who filled multiple prescriptions from this medication group, 16 percent received two prescriptions, and 4 percent received three or more. Psychotropic and neuromuscular drugs were the most commonly prescribed medication classes.

The authors concluded that, in 1999, more than one out of five older patients filled prescriptions for medications that should be avoided in this age group. Clinical and laboratory studies need to be performed to improve the quality of patient-specific alerts.

Curtis LH, et al. Inappropriate prescribing for elderly Americans in a large outpatient population. Arch Intern Med August 9/23, 2004;164:1621-5.

EDITOR'S NOTE: The issue of inappropriate prescription drug use by older patients has been identified for years in various publications, including two studies that were published 10 years ago. In a recent editorial, Steel (1) writes that although these and other studies concerning this issue have been published, "little or nothing" has been done to solve this problem. Various solutions include the development of computerized systems that could identify inappropriate prescriptions written for older patients. According to Steel, (1) if the outcome were this negative in any other setting, there would be a significant public reaction. The bottom line is that physicians and other health care professionals who see older patients and write prescriptions need to be aware of inappropriate medications and should avoid prescribing them to older patients.--K.E.M.

REFERENCE

(1.) Steel K. The time to act is now. Arch Intern Med 2004;164:1603-4.

COPYRIGHT 2005 American Academy of Family Physicians
COPYRIGHT 2005 Gale Group

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