O Conhecimento de diferenças raciais pode evitar reações idiossincrásicas na anestesia?

Nilton Bezerra do Vale; José Delfino; Lúcio Flávio Bezerra do Vale

doi:10.1590/S0034-70942003000200013

Special Article

O Conhecimento de diferenças raciais pode evitar reações idiossincrásicas na anestesia?

Could the understanding of racial differences prevent idiosyncratic anesthetic reactions?

Nilton Bezerra do Vale; José Delfino; Lúcio Flávio Bezerra do Vale

http://dx.doi.org/10.1590/S0034-70942003000200013 Braz J Anesthesiol, vol.53, n2, p.258-277, 2003

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JUSTIFICATIVA E OBJETIVOS: No campo da variabilidade inter-étnica da resposta de drogas anestésicas e adjuvantes existem várias questões sem resposta. Estamos na iminência de sermos capazes de identificar diferenças raciais herdadas que podem prever a resposta de cada paciente aos anestésicos pelo atual desenvolvimento farmacogenético. CONTEÚDO: O conhecimento de fatores inter-étnicos que alteram a resposta à droga permitirá ao anestesiologista evitar reações idiossincrásicas: (1) Branco caucasiano - aumento do efeito diurético da dopamina; apnéia prolongada após succinilcolina ou mivacúrio; arritmias cardíacas após uso de halotano e catecolaminas na síndrome de Riley-Day; ataques agudos de porfiria após tiopental. (2) Negro americano: diferentes abordagens terapêuticas, hipertensão arterial essencial advêm da pior resposta aos anti-hipertensivos de IECA, inibidores do AT1, bloqueadores beta e à clonidina, contrastando com a melhor resposta anti-hipertensiva dos diuréticos, antagonistas de canais de cálcio e clarvedilol; ação vasodilatadora atenuada do isoproterenol (beta2) e uma maior resposta vasodilatadora à nitroglicerina sublingual; menor ação fibrinolítica do t-PA; recuperação mais lenta da anestesia venosa pela associação de remifentanil e propofol; menor glicuronidação do paracetamol e menos analgesia da codeína nos fracos metabolizadores (CYP2D6); a melanina retarda o início da analgesia epidérmica do creme anestésico EMLA; menor midríase pela adrenalina; maior broncoespasmo à metacolina em crianças asmáticas; deficit da G-6-PD nas hemácias eleva o risco de hemólise a drogas oxidativas (10% da população negra). (3) Asiáticos: alterações cinéticas tóxicas da meperidina e codeína; maior duração da ansiólise do diazepam; espasmo coronariano pela injeção de metilergonovina no pós-parto; inter-relação do receptor GABA, das desidrogenases e do comportamento de beber nipônico, contribui para sua maior sensibilidade etanólica. Isoenzimas do citocromo P450 apresentam polimorfismo genético no metabolismo de neuropsicotrópicos e a lenta acetilação da N-acetiltransferase na população equatorial (95%) aumenta a toxicidade de isoniazida e hidralazina. CONCLUSÕES: A presente revisão pretende dar algumas respostas específicas na área da idiossincrasia anestésica relacionada ao efeito da etnicidade sobre a farmacocinética, a farmacodinâmica das drogas e a segurança do paciente cirúrgico, objetivando otimizar uma neuropsicofarmacologia mais individualizada.

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COMPLICAÇÕES, COMPLICAÇÕES

Abstract

BACKGROUND AND OBJECTIVES: There are several unanswered questions about the interethnic variability in anesthetic and adjuvant drugs responses. Current pharmacogenetic developments are taking us to the verge of being able to identify inherited racial differences which could predict individual patients anesthetic response. CONTENTS: The understanding of interethnic factors affecting drug response will allow anesthesiologists to prevent idiosyncratic reactions: (1) Caucasian: increased dopamine diuretic effect; prolonged apnea following succinylcholine or mivacurium; cardiac arrhythmias after halothane and catecholamines in Riley-Day syndrome; acute porphyria episodes after thiopental. (2) Afro-American: different therapeutic approaches, essential arterial hypertension caused by the poorert response to ACEI anti-hypertensives, AT1 blockers, beta-blockers and clonidine, contrasted with the best anti-hypertensive response of diuretics, calcium channel blockers, claverdilol; attenuated isoproterenol-mediated vasodilatation (beta2) and a better vasodilating response to sublingual nitroglycerine; lower t-PA-induced thrombolytic effect; slower recovery from intravenous anesthesia with propofol and remifentanil; less glycuronide conjugation of paracetamol and less pain relief by codeine in weak metabolizers (CYP2D6); melanin slows onset of epidermal analgesia with EMLA anesthetic cream; less epinephrine-induced mydriasis; major metacholine-induced bronchocospasm in asthmatic children; G-6-PD deficit in erythrocytes increases the risk for hemolysis to oxidative drugs in 10% of the Afro-American population. (3) Asians: toxic kinetic changes of meperidine and codeine; longer diazepam-induced anxiolysis; postpartum intravenous ergonovine-induced coronary artery spasm; inter-relationships of GABA receptor, dehydrogenases and Japanese drinking behavior contribute to their higher sensitivity to alcohol. Cytochrome P450 isoenzymes show genetic polymorphisms in neuropsychotropic drugs metabolism and the slow acetylation of N-acetyltransferase in equatorial populations (95%) increases isoniazid and hydrazine toxicity. CONCLUSIONS: This review aimed at answering specific questions in the area of anesthetic idiosyncrasy related to the effect of ethnicity on drugs pharmacokinetics and pharmacodynamics, in addition to surgical patients safety by optimizing a more individualized neuropsychopharmacotherapy.

Keywords

COMPLICATIONS, COMPLICATIONS

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O Conhecimento de diferenças raciais pode evitar reações idiossincrásicas na anestesia?

Could the understanding of racial differences prevent idiosyncratic anesthetic reactions?

Nilton Bezerra do Vale; José Delfino; Lúcio Flávio Bezerra do Vale

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