Anti-inflammatory Analgesics

Research has intensified in an effort to find new nonsteroidal anti-inflammatory drugs (NSAIDs). Long-term therapy with the corticosteroids is often accompanied by various side effects. Bfforts to discover new agents have been limited, for the mo.st part, to structural analogues of active com- 

A significant stimulus to this search was the observation that prostaglandins play a major role in the inflammatory processes. Drugs such as a.spirin and indomcthacin inhibit prostaglandin synthesis in several tissues. Furthermore, almost all classes of NSAIDs strongly inhibit the conversion ofarachidonic acid into pnistaglandin This 

The search for specific inhibitors of cyclooxygenase has opened a new area of research in this field. This cnr.ynic occurs in two forms, cyclooxygenase I (COX-I) and cyclooxygenase 2 (COX-2). COX-1 is a constitutive cn/yme and plays a role in the production of essential prostaglandins. Inhibition of this cn/.yme by all the older, nonsclective NSAIDs is priinurily responsible for a number of their side effects. The COX-2 enzyme is induced in response to the release of several proinflammatory mediators, leading to the inflammatory response and pain. Thus, there was an active search for specific inhibitors of the COX-2 cn/.yme. This has been successful with the approval of three COX-2 inhibitors. discus.sud below. 

Even with the significant advances achieved in the discovery of new and more specific NSAIDs. they all have aceiling cffc ct on their ability to relieve all pain. It is becoming common practice to use combinations of the opioid drugs with NSAIDs to treat severe and intractable pain. These drugs are considered below in their various chemical categories. 

The phannacology of the salicylates and related compounds has been reviewed extensively by Smith. Salicylates. in general, exert their antipyretic action in febrile patients by increasing heat elimination of the body via the mobilization of water and consequent dilution of the blood. This brings about perspiration, causing cutaneous dilatation. 

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ATC M01A N02B S01B Use anti-inflammatory, analgesic,... 

The anti-inflammatory, analgesic, and antimicrobial activities of pyrimi-dotriazinedione derivatives have been investigated (80KFZ39). 

From a series of 5,6-diphenylpyridazines prepared in Italy [91], chloro derivatives of type (20, R = 4-Me2NC6H4, 4-MeOC6H4) have been found to be anti-inflammatory, analgesic and antipyretic agents superior to phenylbutazone when tested in mice or rats. 

Indomethacin (Indocin) Nonsteroidal anti-inflammatory analgesic antipyretic Neutrapenia... 

Patrick Faustino Division of Anti-Inflammatory, Analgesic and Ophthalmic Drug Products, FDA, R 310,9021 Corporate Boulevard, Rockville, Maryland 2085, USA... 

This series of anti-inflammatory, analgesic, and fever-reducing compounds (ibuprofen, naproxene, ketoprofen, fenprofen) can be equally identified as both propionic acid derivatives as well as phenylpropionic acid derivatives. The mechanism of their action is not conclusively known however, it has been suggested that it is also connected with the suppression of prostaglandin synthetase activity. 

Beta-blockers interact with a large number of other medications. The combination of beta-blockers with calcium antagonists should be avoided, given the risk for hypotension and cardiac arrhythmias. Cimetidine, hydralazine, and alcohol all increase blood levels of beta-blockers, whereas rifampicin decreases their concentrations. Beta-blockers may increase blood levels of phenothiazines and other neuroleptics, clonidine, phen-ytoin, anesthetics, lidocaine, epinephrine, monoamine oxidase inhibitors and other antidepressants, benzodiazepines, and thyroxine. Beta-blockers decrease the effects of insulin and oral hypoglycemic agents. Smoking, oral contraceptives, carbamazepine, and nonsteroidal anti-inflammatory analgesics decrease the effects of beta-blockers (Coffey, 1990). 

Piroxicam is a new NSAID and has anti-inflammatory, analgesic and antipyretic activity. It provides effective and long-lasting relief of pain and stiffness. Its convenient once daily dosage provides round the clock relief of symptoms. 

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