IMPACTO DOS POLIMORFISMOS DE CYPs NA METABOLIZAÇÃO DE ANTIPSICÓTICOS TÍPICOS
UMA REVISÃO SISTEMÁTICA
Palavras-chave:
farmacogenética, psicose, antipsicóticos típicos, CYP2D6, polimorfismo, haloperidol
Resumo
Os polimorfismos de isoenzimas do Citocromo P450, especificamente a CYP2D6 e CYP3A4, são um ponto de interesse para a Farmacogenética e impactam na metabolização de antipsicóticos típicos. Essas mutações formam quatro fenótipos de metabolização que influenciam diretamente na segurança e eficácia do tratamento com antipsicóticos típicos. Nesta revisão sistemática de literatura foram selecionados sete estudos que corroboram para achados anteriores quanto a Metabolizadores Lentos e Intermediários apresentarem maiores riscos de desenvolverem efeitos adversos. Quanto a Metabolizadores Ultrarrápidos, estes podem estar expostos a toxicidade dos metabólitos dos antipsicóticos típicos, devido ao rápido aumento destes no organismo. Doses muito baixas de fármacos como o Haloperidol são ineficazes, portanto, subterapêuticas. Conclui-se que a farmacogenética é de grande importância para a segurança do paciente e eficácia da terapia com antipsicóticos típicos.
Referências
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GOMES, C. G.; TONIAZZO, P. B.; SPANEMBERG, L. Abordagem e manejo inicial do paciente psicótico na emergência. Acta méd. (Porto Alegre), 2014.
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SYCHEV, D. A. et al. Genotyping and phenotyping of CYP2D6 and CYP3A iso-enzymes in patients with alcohol use disorder: correlation with haloperidol plasma concentration. Drug metabolism and personalized therapy, v. 32, n. 3, 2017.
SYCHEV, D. A.; BURASHNIKOVA, I. S.; KAZAKOV, R. E. 1846G>A polymorphism of CYP2D6 gene and extrapyramidal side effects during antipsychotic therapy among Russians and Tatars: a pilot study. Drug metabolism and personalized the-rapy, v. 31, n. 4, p. 205–212, 2016.
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TROGRLIĆ, Z. et al. Pharmacogenomic response of low dose haloperidol in critically ill adults with delirium. Journal of critical care, v. 57, p. 203–207, 2020.
BRANDL, E. J.; KENNEDY, J. L.; MÜLLER, D. J. Pharmacogenetics of antipsychot-ics. Canadian journal of psychiatry. Revue canadienne de psychiatrie, v. 59, n. 2, p. 76–88, 2014.
CLINTON, J. E. et al. Haloperidol for sedation of disruptive emergency patients. Annals of emergency medicine, v. 16, n. 3, p. 319–322, 1987.
GASSÓ, P. et al. Relationship between CYP2D6 genotype and haloperidol pharma-cokinetics and extrapyramidal symptoms in healthy volunteers. Pharmacogeno-mics, v. 14, n. 13, p. 1551–1563, 2013.
GOMES, C. G.; TONIAZZO, P. B.; SPANEMBERG, L. Abordagem e manejo inicial do paciente psicótico na emergência. Acta méd. (Porto Alegre), 2014.
ICD-11 for mortality and morbidity statistics. Disponível em:
KANE, Megan. CYP2D6 Overview: Allele and Phenotype Frequencies. 2021 Oct 15. In: Pratt VM, Scott SA, Pirmohamed M, et al., editors. Medical Genetics Summaries [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2012-. Disponível em: https://www.ncbi.nlm.nih.gov/books/NBK574601/
KOOLA, M. M. et al. Association of tardive dyskinesia with variation in CYP2D6: Is there a role for active metabolites? Journal of psychopharmacology (Oxford, En-gland), v. 28, n. 7, p. 665–670, 2014.
LINS, Samuel Lincoln Bezerra. Psicose: diagnóstico, conceitos e reforma psiquiátri-ca. Mental, Barbacena, v. 5, n. 8, p. 39-52, jun. 2007. Disponível em
MARTIN, F. J. et al. Ensembl 2023. Nucleic acids research, v. 51, n. D1, p. D933–D941, 2022.
MELTZER, H. Y. Update on typical and atypical antipsychotic drugs. Annual review of medicine, v. 64, n. 1, p. 393–406, 2013.
MEYER, U. A. Pharmacogenetics – five decades of therapeutic lessons from genetic diversity. Nature reviews. Genetics, v. 5, n. 9, p. 669–676, 2004.
MOREIRA, F. A.; GUIMARÃES, F. S. MECANISMOS DE AÇÃO DOS ANTIPSICÓTI-COS: HIPÓTESES DOPAMINÉRGICAS. Medicina (Ribeirao Preto Online), v. 40, n. 1, p. 63–71, 2007.
PARKHOMENKO, A. A. et al. Correlation of 1846G>A polymorphism of CYP2D6 ge-ne with haloperidol efficacy and safety in patients with alcoholic hallucino-ses. Psychopharmacology bulletin, v. 52, n. 3, p. 58–67, 2022.
RAVYN, D. et al. CYP450 Pharmacogenetic treatment strategies for antipsychotics: A review of the evidence. Schizophrenia research, v. 149, n. 1–3, p. 1–14, 2013.
RITTER, James M. Rang & Dale Farmacologia. Rio de Janeiro: Grupo GEN, 2020. E-book. ISBN 9788595157255. Disponível em: https://integrada.minhabiblioteca.com.br/#/books/9788595157255/. Acesso em: 21 nov. 2023.
SCORDO, M. G. et al. CYP2D6 genotype and antipsychotic-induced extrapyramidal side effects in schizophrenic patients. European journal of clinical pharmacology, v. 56, n. 9–10, p. 679–683, 2000.
STANDAERT, D. G.; WALSH, R. R. Farmacologia da Neurotransmissão Dopaminér-gica. Em: GOLAN, D. E. et al. (Eds.). Princípios de Farmacologia - A Base Fisiopa-tológica da Farmacologia. Rio de Janeiro: Guanabara Koogan, 2021. p. 188–204.
SYCHEV, D. A. et al. The correlation between CYP2D6 isoenzyme activity and ha-loperidol efficacy and safety profile in patients with alcohol addiction during the exacerbation of the addiction. Pharmacogenomics and personalized medicine, v. 9, p. 89–95, 2016.
SYCHEV, D. A. et al. Genotyping and phenotyping of CYP2D6 and CYP3A iso-enzymes in patients with alcohol use disorder: correlation with haloperidol plasma concentration. Drug metabolism and personalized therapy, v. 32, n. 3, 2017.
SYCHEV, D. A.; BURASHNIKOVA, I. S.; KAZAKOV, R. E. 1846G>A polymorphism of CYP2D6 gene and extrapyramidal side effects during antipsychotic therapy among Russians and Tatars: a pilot study. Drug metabolism and personalized the-rapy, v. 31, n. 4, p. 205–212, 2016.
TAKEUCHI, H.; MORI, Y.; TSUTSUMI, Y. Pathophysiology, prognosis and treatment of tardive dyskinesia. Therapeutic advances in psychopharmacology, v. 12, p. 1– 20, 2022.
TROGRLIĆ, Z. et al. Pharmacogenomic response of low dose haloperidol in critically ill adults with delirium. Journal of critical care, v. 57, p. 203–207, 2020.
Publicado
2024-10-28
Seção
Biomedicina
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