Grunberg S M
Division of Medical Oncology, University of Southern California Comprehensive Cancer Center, Los Angeles 90033.
Blood Rev. 1989 Dec;3(4):216-21. doi: 10.1016/0268-960x(89)90029-5.
Nausea and vomiting are the most feared toxicities of chemotherapy. Afferent impulses from the chemoreceptor trigger zone, peripheral sites, the cerebral cortex, or the vestibular center can initiate the emetic reflex. Antiemetic protection therefore requires interruption of appropriate emetogenic pathways. Since the chemoreceptor trigger zone contains numerous dopaminergic neurons, antidopaminergic agents including phenothiazines and metoclopramide have gained importance as antiemetics. However standard dose phenothiazines have limited efficacy while high dose metoclopramide may have excessive toxicity in the non-cisplatin setting. Recent advances have therefore centered on development of new classes of antiemetics. Corticosteroids have excellent activity alone or in combination with other antiemetic agents. Cannabinoids have recently been introduced into commercial use as antiemetics with particular activity against non-cisplatin chemotherapy. Benzodiazepines are active against anticipatory nausea and vomiting and are also used in combination antiemetic regimens. Although the vestibular center seems to have a lesser influence on chemotherapy-induced nausea and vomiting, vestibular blocking agents such as scopolamine may have a potential role as adjunctive antiemetics. Finally, appreciation of the role of serotonin (5-HT3) receptors in both peripheral and central emetic pathways may lead to a new class of antiserotonergic antiemetic agents.
恶心和呕吐是化疗最令人恐惧的毒性反应。来自化学感受器触发区、外周部位、大脑皮层或前庭中枢的传入冲动可引发呕吐反射。因此，止吐保护需要中断适当的致吐途径。由于化学感受器触发区含有大量多巴胺能神经元，包括吩噻嗪类和甲氧氯普胺在内的抗多巴胺能药物已成为重要的止吐药。然而，标准剂量的吩噻嗪类药物疗效有限，而高剂量的甲氧氯普胺在非顺铂治疗环境中可能具有过度毒性。因此，最近的进展集中在新型止吐药的开发上。皮质类固醇单独使用或与其他止吐药联合使用时具有出色的活性。大麻素最近已作为止吐药投入商业使用，对非顺铂化疗具有特殊活性。苯二氮䓬类药物对预期性恶心和呕吐有效，也用于联合止吐方案。尽管前庭中枢似乎对化疗引起的恶心和呕吐影响较小，但东莨菪碱等前庭阻滞剂可能作为辅助止吐药发挥潜在作用。最后，认识到5-羟色胺（5-HT3）受体在外周和中枢呕吐途径中的作用，可能会导致一类新型的抗5-羟色胺止吐药。
