clozapine and Ischemia

Topics: Adult; Antipsychotic Agents; Clozapine; Humans; Intestinal Diseases; Intestines; Ischemia; Male

Inflammatory reactions play an important role in ischemia/reperfusion injury in various organs. Since histamine is closely related to inflammatory reactions and immune responses, effects of postischemic administration of histaminergic ligands on ischemia-induced liver injury were examined in rats. Animals were subjected to warm ischemia for 30 min by occlusion of the left portal vein and hepatic artery under halothane anesthesia, and liver damage was evaluated by assessing plasma concentrations of transaminases after 24 h. Warm ischemia for 30 min provoked severe liver damage after 24 h, and the plasma concentrations of alanine transaminase (ALT) and aspartate transaminase (AST) were 8600 I.U./l and 13100 I.U./l, respectively. Subcutaneous injections of histamine twice, immediately and 6 h after reperfusion (20 mg/kg, each), alleviated liver damage. The plasma concentrations of ALT and AST in the histamine group were 35% and 24% of those in the control group, respectively. Neither mepyramine (3 mg/kg x 2), an H1 antagonist, nor cimetidine (15 mg/kg x 2), an H2 antagonist, affected the outcome in histamine-treated rats. However, thioperamide (5 mg/kg x 2), an H3/H4 antagonist, completely abolished the alleviation caused by histamine. Administration of dimaprit (1-10 mg/kg x 2), an H2/H4 agonist, mimicked the protective effect of histamine, and the effect of dimaprit is reversed by thioperamide, whereas neither H1 nor H2 antagonists altered the outcome caused by dimaprit. Clozapine (15 mg/kg x 2), an H4 agonist, also mimicked the protective effect of histamine. These findings indicate that stimulation of histamine H4 receptors after ischemic events prevents development of reperfusion injury in the liver.

Topics: Alanine Transaminase; Animals; Aspartate Aminotransferases; Clozapine; Dimaprit; Dose-Response Relationship, Drug; Histamine; Ischemia; Liver; Male; Rats; Rats, Wistar; Receptors, G-Protein-Coupled; Receptors, Histamine; Receptors, Histamine H4; Reperfusion Injury; Time Factors

There have been previous reported deaths due to clozapine-induced constipation. In all these cases patients have experienced prior abdominal symptoms over a period of weeks or months.. We report the sudden death due to constipation of a healthy young male patient on clozapine without any known history of prior abdominal symptoms.. Psychiatrists need to be alert to the medical emergencies which can occur in the context of clozapine treatment and also need to make other clinicians who may have contact with their patients aware of these.

Topics: Adult; Antipsychotic Agents; Clozapine; Colon; Fatal Outcome; Fecal Impaction; Humans; Ischemia; Male; Schizophrenia; Time Factors