Morrison G B, Bastian A, Dela Rosa T, Diasio R B, Takimoto C H
NCI-Navy Medical Oncology Branch, National Cancer Institute in Bethesda, MD, USA.
Oncol Nurs Forum. 1997 Jan-Feb;24(1):83-8.
PURPOSE/OBJECTIVES: To describe the pharmacogenetic syndrome of dihydropyrimidine dehydrogenase (DPD) deficiency, which predisposes patients with cancer to potentially lethal adverse reactions following 5-fluorouracil (5-FU)-based chemotherapy.
Published articles, abstracts, and conference proceedings.
Genetic deficiencies in DPD, the rate-limiting enzyme responsible for 5-FU catabolism, may occur in 3% or more of patients with cancer putting them at increased risk for unusually severe adverse reactions (e.g., diarrhea, stomatitis, mucositis, myelosuppression, neurotoxicity) to standard doses of 5-FU. Diagnosis of DPD deficiency must be confirmed by specialized laboratory tests. The principle treatment for DPD-deficient patients with severe acute 5-FU reactions is supportive care; however, the administration of thymidine potentially may reverse severe 5-FU-induced neurologic symptoms such as encephalopathy and coma.
Early recognition of this serious pharmacogenetic syndrome may allow for the modification of future chemotherapy, thus avoiding further life-threatening toxicities.
Nurses must understand the pharmacology, mechanism of action, clinical presentation, potentially lethal risks, and traumatic psychosocial stresses experienced by DPD-deficient patients with cancer receiving 5-FU therapy in order to develop timely interventions and alternative plans of care.
目的/目标：描述二氢嘧啶脱氢酶（DPD）缺乏的药物遗传学综合征，该综合征使癌症患者在接受基于5-氟尿嘧啶（5-FU）的化疗后易发生潜在致命的不良反应。
已发表的文章、摘要和会议记录。
DPD是负责5-FU分解代谢的限速酶，其基因缺陷可能在3%或更多的癌症患者中出现，这使他们对标准剂量的5-FU发生异常严重不良反应（如腹泻、口腔炎、粘膜炎、骨髓抑制、神经毒性）的风险增加。DPD缺乏的诊断必须通过专门的实验室检测来确认。对发生严重急性5-FU反应的DPD缺乏患者的主要治疗方法是支持性护理；然而，给予胸苷可能会逆转严重的5-FU诱导的神经症状，如脑病和昏迷。
早期识别这种严重的药物遗传学综合征可能有助于调整未来的化疗方案，从而避免进一步危及生命的毒性反应。
护士必须了解接受5-FU治疗的DPD缺乏癌症患者的药理学、作用机制、临床表现、潜在致命风险以及经历的创伤性心理社会压力，以便制定及时的干预措施和替代护理计划。
