Aplicação da farmacogenómica na prática médica: exemplo do HLA-B*5701 e reacção de hipersensibilidade ao abacavir
Palavras-chave:
Farmacogenómica, HLA-B*5701, AbacavirResumo
Farmacogenómica é o estudo de variações de características
de ácido desoxirribonucleico (ADN) e ácido ribonucleico (ARN)
relacionadas com resposta a fármacos, sendo considerada central
para o desenvolvimento de estratégias de Medicina personalizada. As reacções adversas a fármacos aumentam a morbilidade,
mortalidade e os custos associados aos cuidados de saúde.
A Farmacogenómica tem o potencial de reduzir as reacções
adversas a fármacos. Na infecção pelo VIH há maior incidência
de reacções de hipersensibilidade. O abacavir é um nucleósido
inibidor da transcriptase reversa utilizado no tratamento da
infecção VIH mas apresenta reacção de hipersensibilidade em
5 a 8% dos doentes. Verificou-se associação do HLA-B*5701
com a reacção de hipersensibilidade ao abacavir, sendo que a
determinação do HLA-B*5701 pode reduzir a incidência desta
reacção de hipersensibilidade
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Referências
Bhathena A, Spear BB. Pharmacogenetics: improving drug and dose selection. Curr Opin Pharmacol. 2008;8:639-646.
Lazarou J, Pomeranz BH, Corey PN. Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies. JAMA. 1998;279:1200-1205.
Bates DW, Spell N, Cullen DJ, Burdick E, Laird N, Petersen LA et al. The costs of adverse drug events in hospitalized patients. JAMA. 1997;277:307-311.
Classen DC, Pestonik SL, EvansRS, Lloyd JF, Burke JP. Adverse drug events in hospitalized patients: excess length of stay, extra costs, and attributable mortality. JAMA. 1997;277:301-306.
WHO, The importance of pharmacovigilance – Safety Monitoring of Medicinal Products, WHO Collaborating Centre for International Drug Monitoring. WHO, 2002. (Disponível em: http://apps.who.int/medicinedocs/pdf/s4893e/s49893e.pdf)
Phillips KA, Veenstra DL, Oren E, Lee JK, Sadee W. Potential role of pharmacogenomics in reducing adverse drug reactions: a systematic review. JAMA. 2001;286:2270-2279.
Coopman SA, Johnson RA, Platt R, Stern RS. Cutaneous disease and drug reactions in HIV infection. N Engl J Med. 1993;23:1670-1674.
Phillips E, Mallal S. Drug hypersensitivity in HIV. Curr Opin Allergy Clin Immunol. 2007;7:324-330.
Phillips EJ, Mallal SA. Pharmacogenetics and the potential for the individualization of antiretroviral therapy. Curr Opin Infect Dis.2008;21:16-24.
Gatanaga H, Honda H, Oka S. Pharmacogenetic information derived from analysis of HLA alleles. Pharmacogenomics. 2008;9:207-214.
Cressey TR, Lallemant M. Pharmacogenetics of antiretroviral drugs for the treatment of HIV-infected patients: an update. Infect Genet Evol. 2007;7:333-342.
Mallal S, Phillips E, Carosi G, Molina JM, Workman C, Tomazic J, et al. HLA-B*5701 screening for hypersensitivity to abacavir. N Engl J Med.
;358:568-579.
Davis CM, Shearer WT. Diagnosis and management of HIV drug hypersensitivity. J Allergy Clin Immunol. 2008;121:826-832.
Hughes AR, Spreen WR, Mosteller M, Warren LL, Lai EH, Brothers CH et al. Pharmacogenetics of hypersensitivity to abacavir: from PGx hypothesis to confirmation to clinical utility. Pharmacogenomics J. 2008;8:1-10.
Hughes CA, Foisy MM, Dewhurst N. Abacavir hypersensitivity reaction: an update. Ann Pharmacother. 2008;42: 387-396.
Hetherington S, Hughes AR, Mosteller M, Shortino D, Baker KL, Spreen W et al. Genetic variations in HLA-B region and hypersensitivity reactions to abacavir. Lancet. 2002;359:1121-1122.
Mallal S, Nolan D, Witt C, Masel G, Martin AM, Moore C et al. Association between presence of HLA-B*5701, HLA-DR7 and HLA-DQ3 and
hypersensitivity to HIV-1 reverse-transcriptase inhibitor abacavir. Lancet. 2002;359:727-732.
Rauch A, Nolan D, Martin A, McKinnon E, Almeida C, Mallal S. Prospective genetic screening decreases the incidence of abacavir hypersensitivity reactions in the Western Australian HIV cohort. Clin Infect Dis. 2006;43:99-102.
Reeves I, Churchill D, Fisher M. Screening for HLA-B*5701 reduces the frequency of abacavir hypersensitivity reactions. Antivir Ther. 2006;11:L11.
Zucman D, de Truchis P, Majerholc C, Stegman S, Caillat-Zucman S. Prospective screening for human leukocyte antigen-B *5701 avoids abacavir hypersensitivity reaction in the ethnically mixed French HIV population. J Acquir Immune Defic Syndr. 2007;45:1-3.
Saag M, Balu R, Brachman P, Martorell C, Burman W, Stancil B et al. High sensitivity of HLA-B*5701 in whites and blacks in immunologically-confirmed cases of hypersensitivity (ABC HSR). Clin Infect Dis. 2008;46:1111-1118.
European AIDS Clinical Society (EACS). Guidelines for the clinical management and treatment of HIV infected adults in Europe. Version 2, December 2007. (Disponível em http://www.eacs.eu/guide/index .htm)
Panel on antiretroviral guidelines for adult and adolescents. Guidelines for the use of antiretroviral agents in HIV-1 infected adult and adolescents. Department of health and human services. January 10, 2011;1-166. (Disponível em:http://www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf)
RCM Ziagen®. (Disponível em http://www.ema.europa.eu/docs/pt_PT/document_library/EPAR_-_Product_Information/human/000252/
WC500050343.PDF
Wang L, McLeod H, Weinshilboum. Genomics and drug response. N EnglJ Med. 2011;364:1144-1153
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