化工设备培训(化工培训).pptVIP

Serotonin and 5-HT3 Receptor Pathway First recognized with high-dose metoclopramide. Development of 5-HT3 antagonists has had dramatic impact: Highly effective in acute vomiting, less effective for delayed events. Optimal use is with dexamethasone. Primary mechanism of action appears to be peripheral. Adapted from: Berger AM et al. In: Cancer: Principles and Practice of Oncology. 6th ed. Lippincott Williams Wilkins; 2001:2869-80. Gralla RJ et al J Clin Oncol 1999;17:2971-94. Antiemetic Subcommittee of the Multinational Association of Supportive Care in Cancer. Ann Oncol 1998;9:811-19. Endo T et al Toxicology 2000;153:189-201. Hesketh PJ et al Eur J Cancer 2003;39:1074-80. Substance P and Neurokinin-1 (NK1) Receptor Pathway High density of substance P/NK1 receptors located in brain regions implicated in the emetic reflex. Primary mechanism of NK1 receptor blockade action appears to be central. Effective for both acute and delayed events. Augments antiemetic activity of a 5-HT3 receptor antagonist and corticosteroid. Adapted from: Hargreaves R J Clin Psychiatry 2002;63(suppl 11):18-24. Saria A Eur J Pharmacol 1999;375:51-60. Hesketh PJ Support Care Cancer 2001;9:350-54. Conceptual Model of Acute Delayed CINV Adapted from Andrews Davis. In: Andrews PLR Sanger GJ (Eds). Emesis in Anti-Cancer Therapy: Mechanisms and Treatment. London: Arnold; 1993:147. 5-HT3-sensitive phase Prokinetic-sensitive phase Steroid-sensitive phase Disrupted gut motility Cell breakdown products Intensity of emesis Time (days) 0 1 2 3 4 5 5HT NK1-sensitive phase Pharmacogenomics Quest for individualized therapy. Identification and characterization of a large number of genetic polymorphisms(biomarkers) in drug metabolizing enzymes and drug transporters may provide substantial knowledge about the mechanisms of inter-individual differences in drug response. Pharmacogenomics Pharmacogenomics - the study of the relationship between specific DNA sequence variations and the actual effect