■多巴胺(D)2,3-受体拮抗剂(RAs)是第一种用于预防化疗引起的恶心和呕吐(CINV)的止吐药。
■八个D2,3-RA,氨磺必利,多潘立酮,氟哌利多,氟哌啶醇,甲氧氯普胺,甲哌嗪,综述了奥氮平和丙氯拉嗪的药代动力学,药效学,止吐作用和副作用。
■自从引入D2,3-RA以来,止吐药如皮质类固醇,已经开发了5-羟色胺(5-HT)3-RAs和神经激肽(NK)1-RAs。经典的D2,3-RA被推荐用于预防低呕吐风险化疗的CINV,但不作为中度或高度(HEC)呕吐风险化疗的止吐方案的固定组成部分。D2,3-RA也用于突破性恶心和呕吐的患者。应该强调,大多数这些药物对多巴胺受体没有选择性。多受体靶向剂,奥氮平,作为四药止吐方案的一部分,推荐用于预防HEC诱导的CINV,包括一个5-HT3-RA,地塞米松和NK1-RA。奥氮平是预防化疗引起的恶心的最有效药物。副作用在各种D2,3-RA中不同。甲哌嗪和多潘立酮具有低风险的锥体外系副作用。多潘立酮和甲氧氯普胺是促动力的,而美哌嗪延迟胃排空,氟哌啶醇不影响胃动力。许多D2,3-RA会增加QTc间期延长的风险;其他副作用包括镇静和直立性低血压。
UNASSIGNED: Dopamine (D)2,3-receptor antagonists (RAs) were the first antiemetics used in the prophylaxis of chemotherapy-induced nausea and vomiting (CINV).
UNASSIGNED: Eight D2,3-RAs, amisulpride, domperidone, droperidol, haloperidol, metoclopramide, metopimazine, olanzapine and prochlorperazine are reviewed focusing on pharmacokinetics, pharmacodynamics, antiemetic effect and side effects.
UNASSIGNED: Since the introduction of D2,3-RAs, antiemetics such as corticosteroids, 5-hydroxytryptamine (5-HT)3-RAs and neurokinin (NK)1-RAs have been developed. The classical D2,3-RAs are recommended in the prophylaxis of CINV from low emetic risk chemotherapy, but not as a fixed component of an antiemetic regimen for moderately or highly (HEC) emetic risk chemotherapy. D2,3-RAs are also used in patients with breakthrough nausea and vomiting. It should be emphasized, that most of these drugs are not selective for dopamine receptors.The multi-receptor targeting agent, olanzapine, is recommended in the prophylaxis of HEC-induced CINV as part of a four-drug antiemetic regimen, including a 5-HT3-RA, dexamethasone and a NK1-RA. Olanzapine is the most effective agent to prevent chemotherapy-induced nausea.Side effects differ among various D2,3-RAs. Metopimazine and domperidone possess a low risk of extrapyramidal side effects. Domperidone and metoclopramide are prokinetics, whereas metopimazine delays gastric emptying and haloperidol does not influence gastric motility. Many D2,3-RAs increase the risk of prolonged QTc interval; other side effects include sedation and orthostatic hypotension.