氯氮平急性中毒所致吸入性肺炎学习

1、氯氮平所致吸入性肺炎吸入性肺炎的简介 吸入性肺炎是由于上呼吸道、口咽部分泌物及食道、胃内容物误吸入下呼吸道引起的肺实质感染。吸入性肺炎的常见原因有误吸、呕吐、咽反射异常、吞咽功能障碍、咳嗽反射减弱等。氯氮平常引起吸入性肺炎 氯氮平为二苯二氮杂卓类抗精神病药，对治疗急、慢性精神分裂症，难治性精神病患者有较好的效果，且费用低廉，但副作用多。流涎是氯氮平的主要副作用之一，也是引起吸入性肺炎的主要原因。氯氮平所致吸入性肺炎的临床表现 氯氮平所致吸入性肺炎的常见症状有：发热、咳嗽、呼吸困难、有时还会出现意识障碍。 氯氮平所致吸入性肺炎的典型体征是：肺部闻及湿罗音。 实验室检查显示：白细胞计数及比值升高。

2、 影像学改变有：肺内单发或多发斑片状模糊影。氯氮平引起吸入性肺炎的机制 使用氯氮平治疗的患者中有31-54%的患者存在流涎。流涎常常出现在氯氮平治疗的早期、并且与加量过快有关。 在抗精神病药物中，氯氮平的抗胆碱能效应最强，人们预期氯氮平会导致口干，然而事实与预期相反，氯氮平常引起流涎。氯氮平引起吸入性肺炎的机制 有人认为，氯氮平可通过激动唾液腺腺泡上的胆碱能M4受体和2肾上腺素能受体，导致唾液分泌增加。 然而有研究显示，流涎的患者与正常人群相比，唾液分泌量并无增加。因此氯氮平所致流涎可能与抗多巴胺能作用导致的吞咽障碍有关。 此外，由于睡眠时喉肌处于松驰状态,吞咽反射减弱。在睡眠姿势不当时,尤其

3、是仰卧时易受涎液返流经会厌部渗入支气管,从而引起肺炎。病例讨论Mr. C, a 26 year old male with schizophrenia paranoid type and a long history of numerous psychiatric hospitalizations was admitted to our inpatient unit for treatment of difficulty sleeping, paranoia, auditory hallucinations and inability to function following non-com

4、pliance with his medication (risperidone). His medical history was unremarkable. Complete blood count, basic metabolic panel, and thyroid stimulating hormone levels were within normal limits. On our inpatient unit, he was found to be irritable, guarded, internally preoccupied, gesturing and talking

5、to himself. His pastpsychiatric history was significant for failure to respond to multiple typical and atypical antipsychotics(chlorpromazine, fluphenazine, perphenazine, quetiapine, olanzapine, aripiprazole, ziprazidone). He had partial response to risperidone described by hisoutpatient psychiatris

6、t as moderate reduction of paranoia and hallucination.Mr. C was restarted on risperidone which was titrated up to 4 mg twice a day. He remained paranoid, disorganized with auditory hallucinations telling him that he was the son of a famous singer. On day 10 of admission, haloperidol was added and ti

7、trated up to 10 mg bid. Despite being on two antipsychotics for more than 3 weeks, Mr. C didnt improve and the decision was made to discontinue risperidone, haloperidol and start clozapine. C先生是一位26岁的偏执型精神分裂症患者，曾多次住院。曾用过多种抗精神病药，包括奥氮平、喹硫平、阿立哌唑、奋乃静、氯丙嗪，疗效欠佳。C先生对利培酮反应为部分有效，入院时利培酮的剂量为4mg Bid，仍存在妄想、言行紊乱、

8、幻听。 入院第10天联合使用氟哌啶醇10mg Bid。联合用药3周后，症状无缓解，遂停用利培酮和氟哌啶醇，开始使用氯氮平治疗。病例讨论Four days after clozapine was begun (25 mg orally in the morning, 50 mg orally at bedtime), Mr. C experienced side effects from the medication, including severe drooling, sedation, headache and tachycardia. The following day, the pat

9、ient spiked a fever of 103F and developed altered mental status with difficulty breathing. He was transferred to the emergency room where findings on physical examination and radiographic evidence of an infiltrate lead to a diagnosis of pneumonia. Further investigations revealed a positive sputum cu

10、lture for peptostreptococcus, as the causative organism. 氯氮平使用到第4天，患者出现药物副反应，表现为：唾液分泌增多、镇静、头痛和心动过速，此时氯氮平的剂量为：早25mg、晚50mg。第2天，患者出现发热、呼吸困难、意识改变。体查及胸片检查提示为肺炎。痰培养显示消化道链球菌阳性。诊断为吸入性肺炎。予头孢夫辛和氟喹诺酮治疗，并停用氯氮平。经过抗生素治疗，患者的肺部感染治愈。使用氟哌啶醇20mg Bid抗精神病治疗，疗效一般，无明显药物副反应。病例讨论The commonly cited risk factors for developin

11、g aspiration pneumonia include dysphagia, esophageal dysfunction, impairment of consciousness, and increased bacterial inoculum. Sialorrhea likely contributed to aspiration pneumonia in our patient. Our patient developed hypersalivation and sedation 13 days after initiation of clozapine. This is in

12、keeping with data that shows the most significant increase in sialorrhea during the second and third weeks of clozapine titration . One day after he was noted to have profuse salivation, Mr. C developed pyrexia. The time course is highly suggestive of aspiration pneumonia, which was confirmed by chest x-ray and sputum culture. 导致吸入性肺炎的常见原因有：吞咽困难、食道功能障碍、意识障碍。在本病例中，流涎是导致吸入性肺炎的原因。氯氮平导致的唾液分泌增多往往发生在用药的第23周。这位患者是在使用氯氮平13天后出现唾液分泌增多和镇静。患者是在大量分泌唾液之后出现发热的，从时间关系说明吸入性肺炎的可能性大，另外胸片的结果和痰培养发现致病菌为消化道链球菌可证实这一推论。氯氮平所致吸入性肺炎的处理（一） 吸入性肺炎的处理：临床医生需要对氯氮平导致的吸入性肺炎保持高度警惕。吸入性肺炎是氯氮平治疗导致死亡的独立因素之一。一旦发生吸入性