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Нестероидные противовоспалительные препараты

план на продолжение статьи Нестероидные противовоспалительные препараты

Examples

NSAIDs can be broadly classified based on their chemical structure. NSAIDs within a group will tend to have similar characteristics and tolerability. There is little difference in clinical efficacy between the NSAIDs when used at equivalent doses. Rather, differences between compounds tended to be with regards to dosing regimens (related to half-life), route of administration, and tolerability profile. Some more common examples are given below.

Paracetamol (acetaminophen), owing to its inhibitory action on cyclooxygenase, is sometimes grouped together with the NSAIDs. Paracetamol, however, does not have any significant anti-inflammatory properties and is not a true NSAID. Though it has not been clearly elucidated, it is suspected that this lack of anti-inflammatory action may be due to the paracetamol inhibiting cyclooxygenase predominantly in the central nervous system. There is also some speculation that paracetamol acts through the inhibition of the recently discovered COX-3 isoform (see below).

Салицилаты

• Аспирин
• Метил салицилат
• Diflunisal
• Banorylate
• Faislamine
• Амоксиприн

Производные бензол-уксусной кислоты

• Диклофенак
• Индометацин
• Сулиндак

2-Arylpropionic acids (profens)

• Ибупрофен
• Кетопрофен
• Напроксен
• Carprofen
• Фенопрофен
• Кеторол

N-Arylanthranilic acids (fenamic acids)

• Mefenamic acid
• Mcelofenamate sodium

Оксикамы

• Пикроксикам
• Мелоксикам
• Лорноксикам
• Теноксикам

Коксибы

• Целекоксиб
• Рофекоксби (изъят из продажи)
• Вальдекоксиб (изъят из продажи)

Sulphonanilides

• Нимесулид

Newer NSAIDs: selective COX inhibitors

COX-2 inhibitors

The discovery of COX-2 in 1991 by Daniel L. Simmons at Brigham Young University raised the hope of developing an effective NSAID without the gastric problems characteristic of these agents. It was thought that selective inhibition of COX-2 would result in anti-inflammatory action without disrupting gastroprotective prostaglandins.

COX-1 is a constitutively expressed enzyme with a "house-keeping" role in regulating many normal physiological processes. One of these is in the stomach lining, where prostaglandins serve a protective role, preventing the stomach mucosa from being eroded by its own acid. When non-selective COX-1/COX-2 inhibitors (such as aspirin, ibuprofen, and naproxen) lower stomach prostaglandin levels, these protective effects are lost and ulcers of the stomach or duodenum and potentially internal bleeding can result. COX-2 is an enzyme facultatively expressed in inflammation, and it is inhibition of COX-2 that produces the desirable effects of NSAIDs.

The relatively selective COX-2 inhibiting oxicam, meloxicam, was the first step towards developing a true COX-2 selective inhibitor. Coxibs, the newest class of NSAIDs, can be considered as true COX-2 selective inhibitors, and include celecoxib, rofecoxib, valdecoxib, parecoxib and etoricoxib.

Controversies with COX-2 inhibitors

While it was hoped that this COX-2 selectivity would reduce gastrointestinal adverse drug reactions (ADRs), there is little conclusive evidence that this is true. The original study touted by Searle (now part of Pfizer), showing a reduced rate of ADRs for celecoxib, was later revealed to be based on preliminary data - the final data showed no significant difference in ADRs when compared with diclofenac.

Rofecoxib however, which has since been withdrawn, had been shown to produce significantly fewer gastrointestinal ADRs compared to naproxen. (Bombardier et al, 2000). This study, the VIGOR trial, raised the issue of the cardiovascular safety of the coxibs - a statistically insignificant increase in the incidence of myocardial infarctions was observed in patients on rofecoxib. Further data, from the APPROVe trial, showed a relative risk of cardiovascular events of 1.97 versus placebo - a result which resulted in the worldwide withdrawal of rofecoxib in October 2004.

COX-3 inhibitors

Simmons also co-discovered COX-3 in 2002 and analyzed this new isozyme's relation to paracetamol (acetaminophen), arguably the most widely used analgesic drug in the world. (Chandrasekharan et al, 2002). The authors postulated that inhibition of COX-3 could represent a primary central mechanism by which these drugs decrease pain and possibly fever.

The clinical ramifications and knowledge of COX isozymes are rapidly expanding and may offer significant hope for future treatments of pain, inflammation, and fever.