Brazilian Journal of Anesthesiology
https://app.periodikos.com.br/journal/rba/article/doi/10.1590/S0034-70942004000300017
Brazilian Journal of Anesthesiology
Review Article

Analgésicos inibidores específicos da ciclooxigenase-2: avanços terapêuticos

Specific cyclooxygenase-2 inhibitor analgesics: therapeutic advances

Wilson Andrade Carvalho; Rosemary Duarte Sales Carvalho; Fabrício Rios-Santos

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Resumo

JUSTIFICATIVA E OBJETIVOS: Os antiinflamatórios não-esteroidais (AINE) estão entre as drogas mais prescritas e usadas no mundo, incluindo a utilização em Anestesiologia. O propósito desta revisão é discutir alguns aspectos atuais da bioquímica da ciclooxigenase, que vem servindo de base para o desenvolvimento dos novos AINE. CONTEÚDO: Estas drogas exercem suas ações principalmente através da inibição da ciclooxigenase (COX), a enzima chave que catalisa a conversão de ácido araquidônico em prostaglandinas e tromboxanos. Pelo menos duas isoformas da COX já foram identificadas, a COX-1, que é constitutivamente expressa na maioria dos tecidos, e a COX-2, que é uma forma induzível da enzima localizada principalmente nas células e tecidos envolvidos em processos inflamatórios. Com a descoberta da COX-2 e a determinação de sua estrutura, foi possível desenvolver drogas mais seletivas que reduzem a inflamação sem afetar a COX-1, protetora do estômago e rins, dando origem a uma nova geração de compostos antiinflamatórios denominados de inibidores específicos da COX-2. CONCLUSÕES: Embora estes compostos de última geração apresentem menor toxicidade para o trato gastrintestinal, outros efeitos adversos graves têm sido observados, incluindo insuficiência renal e efeitos cardiovasculares, como o infarto agudo do miocárdio e a trombose. A despeito destes efeitos colaterais, estes novos fármacos estão sendo testados em outras condições clínicas, principalmente no tratamento preventivo do câncer e da doença de Alzheimer.

Palavras-chave

ANTIINFLAMATÓRIOS, DOR, DOR

Abstract

BACKGROUND AND OBJECTIVES: Nonsteroidal Anti-inflammatory Drugs (NSAIDs) are among the most widely prescribed drugs, including for Anesthesiology. This review aimed at discussing some current cycloxygenase biochemical aspects, which have provided the basis for the development of new analgesic and anti-inflammatory drugs. CONTENTS: These drugs primarily act by inhibiting cycloxygenase (COX), which is the key-enzyme catalyzing the conversion of arachidonic acid into prostaglandins and thromboxane. At least two COX isoforms have already been identified: COX-1, which is constitutively expressed in most tissues, and the inducible enzyme COX-2, which is primarily found in inflammatory cells and tissues. The discovery of COX-2 has enabled the development of more selective drugs to decrease inflammation without affecting COX-1 that protects stomach and kidneys and giving origin to a new generation of anti-inflammatory compounds called specific COX-2 inhibitors. CONCLUSIONS: Although there is significantly lower gastrointestinal toxicity in patients treated with selective COX-2 inhibitors, other severe adverse effects have been observed, including renal failure and cardiovascular effects, such as myocardial infarction acute and thrombosis. Despite these potential side effects, these new drugs are being tested in different clinical conditions, especially in cancer prevention and Alzheimer's disease.

Keywords

ANTI-INFLAMMATORY, PAIN, PAIN

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