RESUMO
Imatinib mesylate (Gleevec) or Glivec), a small molecule tyrosine kinase inhibitor for the treatment of chronic myeloid leukaemia, has been said to herald the dawn of a new era of rationally designed, molecularly targeted oncotherapy. Lurking on the same new horizon, however, is the age-old spectre of drug resistance. This review sets the intoxicating clinical perspective against the more sobering laboratory evidence of such divergent mechanisms of imatinib resistance as gene amplification and stem cell quiescence. Polychemotherapy has already been considered to combat resistance, but a more innovative, as yet unformulated, approach may be advocated.
Assuntos
Antineoplásicos/uso terapêutico , Inibidores Enzimáticos/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Piperazinas/uso terapêutico , Pirimidinas/uso terapêutico , Trifosfato de Adenosina/metabolismo , Benzamidas , Resistencia a Medicamentos Antineoplásicos , Proteínas de Fusão bcr-abl , Amplificação de Genes , Genes MDR , Humanos , Mesilato de Imatinib , Células-Tronco Neoplásicas/efeitos dos fármacos , Orosomucoide/metabolismo , Piperazinas/metabolismo , Piperazinas/farmacologia , Pirimidinas/metabolismo , Pirimidinas/farmacologiaRESUMO
In a survey of 176 drug addict deaths occurring from 1987 to 1992 inclusive, in North and West London, nine were HIV positive, eight were hepatitis B positive, and two were positive for both infections; 63% were injectors. Of the 176 deaths, 115 were directly related to drug poisoning, 38 were due to complications of drug ingestion and 23 were from unrelated causes. No increase in the incidence of suicide was observed in addicts who knew that they were HIV positive.
Assuntos
Soropositividade para HIV/epidemiologia , Hepatite B/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/mortalidade , Adolescente , Adulto , Feminino , Soropositividade para HIV/complicações , Hepatite B/complicações , Humanos , Londres/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Transtornos Relacionados ao Uso de Substâncias/complicações , Transtornos Relacionados ao Uso de Substâncias/epidemiologiaRESUMO
A list of drug levels found in cases of fatal self-poisoning is presented here. These are all cases where only one drug was found and the cause of death in each case was attributed to an overdose of that particular drug. For each case a full drug screen was carried out. In general thin-layer chromatography (TLC) was used as the initial screening technique and any positive findings were then confirmed by gas liquid chromatography (GLC) and high performance liquid chromatography (HPLC). When the drug had been positively identified, the blood level was measured.