Anti-inflammatory agent indomethacine

In humans, the principal metabolic pathway of the anti-inflammatory agent indomethacin (4.92) proceeds through O-demethylation to yield 4.94,... 

J, Walter PB, Tomer KB, Barrett JC, Mason RP. Biomarkers of oxidative stress study 111. Effects of the nonsteroidal anti-inflammatory agents indomethacin and meclofenamic acid on measurements of oxidative products of lipids in CCI4 poisoning. Free Radic. Biol. Med. 2005 38 711. 

In addition to the agents in this section, sulindac and indomethacin (see Nonsteroidal Anti-inflammatory Agents monograph) and phenylbutazone and oxyphenbutazone (see individual monographs) are indicated for the treatment of gout. 

Many interactions with lithium have been described. Thiazide and loop diuretics decrease lithium excretion predisposing to serious lithium toxicity. Also non-steroidal anti-inflammatory agents, especially indomethacin can increase the risks for lithium toxicity due to decreased renal excretion. 

Colchicine (an alkaloid obtained from meadow saffron or autumn crocus) may be used both diagnostically to ascertain the presence of gout and prophylactically to prevent its further occurrence. Usually, 0.5-mg oral doses of colchicine are given hourly until either the therapeutic effects appear or the side effects develop. In addition to colchicine, phenylbutazone, indomethacin, adrenocorticotropic hormone (ACTH), and steroidal anti-inflammatory agents may be used to treat the acute attack of gout. 

Great care should be exercised in prescribing colchicine for elderly patients, and for those with cardiac, renal, hepatic, or gastrointestinal disease. In these patients and in those who do not tolerate or respond to colchicine, indomethacin or another nonsteroidal anti-inflammatory agents (NSAID) is preferred. 

Indomethacin, cyclooxygenase, and hypertension Arthritis and hypertension frequently coexist, and certain nonsteroidal anti-inflammatory agents antagonize the action... 

Indomethacin is a non-steroidal, anti-inflammatory agent with anti-pyretic and analgesic properties discovered and developed by the Merck Sharp and Dohme Research Laboratories(1). 

Experimental and clinical observations indicate that non-steroidal anti-inflammatory agents (NSAIDs, see p. 403) such as aspirin and indomethacin are effective in controlling diarrhea. This antidiarrheal action is probably due to inhibition of prostaglandin synthesis. Bismuth subsalicylate (pepto-bismol), used for traveler s diarrhea, decreases fluid secretion in the bowel its action may be due to its salicylate component. 

Non-Steroidal Anti-Inflammatory Agents (NASID), like indomethacin and acetyl-salicylic acid (aspirin), induce gastric lesions in man and in experimental animals by inhibition of gastric cyclooxygenase (COX) resulting in less formation of prostacyclin, the predominant prostanoid produced in the gastric mucosa. 

There are two major groups of synthetic compounds which have cannabin-oid activity, but which differ chemically from the tricyclic THC-like canna-binoids the bicyclic cannabinoids, exemplified by compound CP55940 (23), and the (aminoalkyl)indoles exemplified by pravadoline (24a). A detailed SAR analysis of these groups of compounds is beyond the scope of this review. The bicyclic cannabinoids and derivatives have been reviewed previously [105] recent publications deal mainly with related tricyclic non-classical cannabinoids [106] and with the (aminoalkyl)indoles [92, 107]. It is of interest to note that while the bicyclic cannabinoids were originally prepared as simplified cannabinoids, the cannabinoid-type activity of the (ami-noalkyl)indoles was discovered by serendipity. These compounds were synthesized in a project aimed at the discovery of novel nonsteroidal anti-inflammatory agents presumably based on the indomethacin structure. However, while they did not possess anti-inflammatory properties, they were found to be antinociceptive, and to inhibit the electrically evoked contractions in a mouse vas deferens muscle preparation. This led to binding experi-... 

Nonsteroidal anti-inflammatory agents salicylates Indomethacin Clomiphene... 

Pain killers and anti-inflammatory agents may also cause a problem. Watch out for acetaminophen (Tylenol), naproxen (OTC Aleve or Rx Naprosyn), and ibuprofen (Advil, Motrin). The prescription-only anti-inflammatory drugs diclofenac (Voltaren) and indomethacin (Indocin) can also increase blood pressure. 

Recently, we have reported the in vivo and in vitro anti-inflammatory activity of two saikosaponins isolated from B. rigidum, budlejasaponin IV and sandrosaponin I, in order to establish the possible real value of these kinds of compounds as anti-inflammatory agents [44]. We showed that saikosaponins inhibited the mouse ear edema induced by topical administration of phorbol myristate acetate (PMA). Saikosaponins, at a dose of 1 mg/ear, significantly inhibited swelling and were as potent as the reference drug indomethacin at 3 mg/ear. These findings were supported by vascular permeability analysis [Table 10 and Fig. (4)]. 

FIGURE 36.37 Anti-inflammatory agents representing the aroylpropi- FIGURE 36.38 The hexenoic analog of indomethacin as a bioprecursor... 

As with indomethacin analogs, the in vivo biological activity of several a-methylphenylacetic acids is invariably associated with the dextro rotatory isomer of the sinister absolute configuration. Thus the stereo-specificity of the a-carbon atom of these anti-inflammatory agents appears to be identical with that of plant growth hormones. 

Nonsteroidal anti-inflammatory agents such as indomethacin also have been used for tocolysis. The mechanism of action is to inhibit cervical prostaglandin activity. The drug is first given orally or rectally in a dose of 50 to 100 mg, followed by an oral dose of 25 to 50 mg every 6 hours. An increased rate of premature constriction of the duems arteriosus has been noted in infants. ... 

It is now a well-known fact that nonsteroidal anti-inflammatory agents such as acetylsalicylic acid, indomethacin, and ibuprofen are potent, irreversible inhibitors of fatty acid cyclooxygenase. Furthermore, significant evidence has appeared in the literature that indicates that steroidal antiinflammatory agents may prevent the release of arachidonic acid from the more complex lipids to which it is normally attached. 

Reversible inhibitors of COX 1 and COX 2, with analgesic, antipyretic, and antiinflammatory actions, include ibuprofen, naproxen, indomethacin, ketorolac, and sulindac. When used as anti-inflammatory agents, they are usually no more effective than ASA, but they may be better tolerated. All have antiplatelet actions (reversible) at moderate (not low) doses and cause bleeding tendencies. 

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