该病例报告研究了氯氮平/去甲氯氮平比率与便秘和麻痹性肠梗阻的发生之间的可能相关性。我们介绍了一名42岁的患者,该患者被诊断患有分裂情感障碍,正在接受氯氮平治疗。尽管用氯氮平强化治疗,氟哌啶醇,丙戊酸和双周电惊厥治疗超过一年,花哨的精神病症状和波动的情绪波动持续存在。因此,丙戊酸被卡马西平取代,几种CYP450酶的有效诱导剂。为了维持氯氮平的血浆水平,氟伏沙明,CYP1A2抑制剂,在此转换之前以25mg的剂量引入。加完卡马西平后,氯氮平水平显著下降,需要将氟伏沙明剂量增加至50mg。五周后,患者被送往综合医院,诊断为麻痹性肠梗阻。用灌肠剂治疗被证明是有效的。药物浓度分析显示,入院前几周,去甲氯氮平水平增加了2.5倍。导致反向氯氮平/去甲氯氮平的比例。用氯氮平治疗,卡马西平和氟伏沙明继续治疗,因为患者显示卡马西平的临床改善。同时,开始了强化泻药方案.两周后,该患者因怀疑麻痹性肠梗阻和粪便呕吐而再次入院,再次显示反向氯氮平/去甲氯氮平比率。我们讨论了该患者发生麻痹性肠梗阻的潜在机制,包括氯氮平和去甲氯氮平对毒蕈碱M3受体的拮抗作用,以及去甲氯氮平对δ阿片受体的激动作用。该病例强调了氯氮平/去甲氯氮平比率和绝对去甲氯氮平水平作为氯氮平治疗患者便秘和麻痹性肠梗阻的危险因素的潜在意义。
This
case report examines the possible correlation between the clozapine/norclozapine ratio and the occurrence of constipation and paralytic ileus. We present the
case of a 42-year-old patient diagnosed with schizoaffective disorder undergoing clozapine therapy. Despite intensive treatment with clozapine, haloperidol, valproic acid and biweekly electroconvulsive therapy sessions for over a year, florid psychotic symptoms and fluctuating mood swings persisted. Therefore, valproic acid was replaced by
carbamazepine, a potent inducer of several CYP450-enzymes. To maintain clozapine plasma levels, fluvoxamine, a CYP1A2-inhibitor, was introduced at a dose of 25 mg before this switch. After addition of carbamazepine, there was a significant decline in clozapine levels, necessitating an increase in fluvoxamine dosage to 50 mg. Five weeks later the patient was admitted to a general hospital with a diagnosis of paralytic ileus. Treatment with enemas proved effective. Drug concentration analysis revealed a 2.5-fold increase in norclozapine levels in the weeks preceding hospital admission, resulting in an inverted clozapine/norclozapine ratio. Treatment with clozapine, carbamazepine and fluvoxamine was continued as the patient demonstrated clinical improvement on
carbamazepine. Concurrently, an intensive laxative regimen was initiated. Two weeks later, the patient was readmitted to the general hospital due to suspected paralytic ileus and faecal vomiting, once again displaying an inverted clozapine/norclozapine ratio. We discuss potential mechanisms contributing to the occurrence of the paralytic ileus in this patient, including the antagonism of muscarinic M3 receptors by both clozapine and norclozapine, as well as the agonism of delta-opioid receptors by norclozapine. This
case highlights the potential significance of both the clozapine/norclozapine ratio and absolute norclozapine levels as risk factors for constipation and paralytic ileus in patients on clozapine therapy.