NSAID agents

Therapeutic uses Phenylbutazone is prescribed chiefly in shortterm therapy of acute gout and in acute rheumatoid arthritis when other NSAID agents have failed. The usefulness of phenylbutazone is limited by its toxicity. Aspirin and newer NSAIDs are superior to phenylbutazone in most applications. 

NSAID agents can usefully be divided by chemical groups because there is some consistency of pharmacology within these groups. 

Fenoprofen is a NSAID agent, which decreases inflammation, pain, and fever, probably through inhibition of cyclooxygenase activity and prostaglandin synthesis. It is indicated in the symptomatic relief for rheumatoid arthritis, osteoarthritis, and mild to moderate pain. 

Busch U, HeinzelG,NaijesH. Effect of food on pharmacokinetics of meloxicarn, anew non steroidal anti-inflammatory drug (NSAID). Agents Actions (1991) 32, 52-3. 

This is the equimolecular salt of phenylbutazone and piperazine (the pro-drug of phenylbutazone), to which two patients developed a contact allergy one from suppositories (Brando and Foussereau 1982), the other from tablets (Dorado Bris et al. 1992) containing this non-steroidal anti-inflammatory (NSAID) agent. In the first case, piperazine was the only other substance tested and a positive reaction occurred in the second patient, both ingredients of pyrazinobutazone produced positive patch-test results. 

A new generation of antiinflammatory agents having immunosuppressive activity has been developed. The appearance of preclinical and clinical reports suggest that these are near entry to the pharmaceutical market. For example, tenidap (CP-66,248) (12) has been demonstrated to inhibit IL-1 production from human peripheral blood monocytes in culture (55). Clinically, IL-1 in synovial fluids of arthritic patients was reduced following treatment with tenidap. Patients with rheumatoid or osteoarthritis, when treated with tenidap, showed clinical improvement (57,58). In addition to its immunological effects, tenidap also has an antiinflammatory profile similar to the classical NSAIDs (59). Other synthetic inhibitors of IL-1 production are SKF 86002 (20) andE-5110 (21) (55). 

Nonsteroidal Antiinflammatory Drugs. Nonsteroidal antiinflammatory dmgs (NSAIDs) include, among the numerous agents of this class, aspirin (acetylsaflcyhc acid), the arylacetic acids indomethacin and sulindac, and the arylpropionic acids, (5)-(147) and (R)-(148) ibuprofen, (5)-(149) and (R)- (150), flurbiprofen naproxen (41), and fenoprofen (see Analgesics, antipyretics, and antiinflammatory agents Salicylic acid and related compounds). 

The most common NSAID is aspirin, or acctylsalicvlic acid, whose use goes back to the late 1800s. It had been known from before the time of Hippocrates in 400 bc that fevers could be lowered by chewing the bark of willow trees. The active agent in willow bark was found in 1827 to be an aromatic compound called salicin, which could be converted by reaction with water into sal- icy I alcohol and then oxidized to give salicylic acid. Salicylic acid... 

Indomethacin treatment is associated with a high incidence (30%) of side effects typical for those seen with other NSAIDs (see above). Gastrointestinal side effects, in particular, are more frequently observed after indomethacin than after administration of other NSAIDs. The market share of indomethacin ( 5%) is therefore low compared to that for other non-steroidal anti-rheumatic agents. 

Oxicams, e.g. piroxicam, tenoxicam, meloxicam and lornoxicam are non-specific inhibitors of COX. Like diclofenac, meloxicam inhibits COX-2 ten times more potently than COX-1. This property can be exploited clinically with doses up to 7.5 mg per day, but at higher doses COX-1-inhibition becomes clinically relevant. Since the dose of meloxicam commonly used is 15 mg daily, this agent cannot be regarded as a COX-2-selective NS AID and considerable caution needs to be exercised when making comparisons between the actions of meloxicam and those of other conventional NSAIDs. The average daily dose in anti-rheumatic therapy is 20 mg for piroxicam and tenoxicam, 7.5-15 mg for meloxicam and 12-16 mg for lornoxicam. Oxicams have long elimination half-lives (lornoxicam 3-5 h, meloxicam - 20 h, piroxicam 40 h and tenoxicam 70 h). 

The indications for these agents are in principle identical to those of the non-selective NSAIDs although the substances have not yet received approval for the whole spectrum of indications of the conventional NSAIDs. Because they lack COX-1-inhibiting properties, COX-2-selective inhibitors show fewer side effects than conventional NSAIDs. However, they are not free of side effects because COX-2 has physiological functions that are blocked by the COX-2 inhibitors. The most frequently observed side effects are infections of the upper respiratory tract, diarrhoea, dyspepsia, abdominal discomfort and headache. Peripheral oedema is as frequent as with conventional NSAIDs. The frequency of gastrointestinal complications is approximately half that observed with conventional NSAIDs. 

Drug allergies rival food allergies in respect to frequency. Among the most frequent causes, antibiotics, NSAIDs, but also radiocontrasts and various other agents administered during the perioperative period are the most common causes [1]. 

Contrary to other elicitors of non-immune anaphylactic reactions (radiocontrast media, neuromuscular blocking agents, non-steroidal anti-inflammatory drugs (NSAIDs)) where there are at least hypothetical concepts regarding the pathomecha-nism of these reactions via increased mediator release (e.g. histamine release, shift in arachidonic acid metabolism from prostaglandins towards leukotrienes, etc.) [26], there is almost no literature regarding the pathomechanism of these reactions after LA application. 

NSAIDs or acetaminophen may be used as adjunctive agents in the appropriate patient... 

With the availability of NSAIDs with COX-2 selectivity, clinicians postulated that these agents would avoid the need to add an additional prophylactic agent to therapy in patients with PUD risk factors. However, selective COX-2 inhibitors have not been shown to be any more effective than the combination of a PPI and a non-selective NSAID in reducing the incidence of ulcers, and questions remain regarding their long-term cardiovascular safety. 

Longer-term studies evaluating the cardiovascular risks associated with the use of COX-2 inhibitors have found a higher incidence of cardiovascular mortality with the use of these agents compared to traditional NSAIDs.29,33,34 This prompted the withdrawal of both rofecoxib and valdecoxib from the market and the inclusion of a black box warning in... 

Determine if drug therapy may be contributing to ARF. Consider not only drugs that can directly cause ARF (e.g., aminoglycosides, amphotericin B, NSAIDs, cyclosporine, tacrolimus, ACE inhibitors, and ARBs), but also drugs that can predispose a patient to nephrotoxicity or prerenal ARF (i.e., diuretics and anti hypertensive agents). 

Aspirin, non-acetylated salicylates, and other NSAIDs have analgesic, antipyretic, and anti-inflammatory actions. These agents inhibit cyclooxygenase (COX-1 and COX-2) enzymes, thereby preventing prostaglandin synthesis, which results in reduced nociceptor sensitization and an increased pain threshold. NSAIDs are the preferred agents for mild to moderate pain in situations that are mediated by prostaglandins (e.g., rheumatoid... 

NSAIDs are classified as non-selective (they inhibit COX-1 and COX-2) or selective (they inhibit only COX-2) based on degree of cyclooxygenase inhibition. COX-2 inhibition is responsible for anti-inflammatory effects, while COX-1 inhibition contributes to increased GI and renal toxicity associated with non-selective agents. Since the antiplatelet effect of non-selective NSAIDs is reversible, concurrent use may reduce the... 

The role of NSAIDs and opioids in chronic non-malignant pain has been discussed however, a review of adjuvant agents... 

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