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Pleural disease induced by drugs
Published in Philippe Camus, Edward C Rosenow, Drug-induced and Iatrogenic Respiratory Disease, 2010
Clozapine, an atypical antipsychotic drug, has had success in the treatment of schizophrenia that is refractory to conventional neuroleptics. Adverse effects of clozapine include seizures, sialorrhea, agranulocytosis, hepatotoxicity, pancreatitis and hyperglycaemia. There have been a few reports of clozapine-induced pleural effusions, and there has been a single report of clozapine-induced polyserositis.14 A pleural effusion appears to occur within the first 2–3 weeks of therapy. The effusions are bilateral or unilateral, usually accompanied by fever, and may be associated with haematuria and hepatocellular dysfunction. Pleural fluid analysis in a single patient revealed a neutrophil predominant exudate; pleural fluid eosinophilia has been reported on several occasions. Three cases of clozapine-induced polyserositis and three of isolated pleural effusions have been reported. In one patient, the erythrocyte sedimentation rate (ESR) was 90 mm/h without peripheral or pleural fluid eosinophilia. Pleural fluid in another patient was straw-coloured with 233 nucleated cells/μL with 74 per cent mono-nuclear cells and no eosinophilia; total protein was 2.4 g/dL with a serum/protein total ratio of 0.37, and the lactate dehydrogenase (LDH) was 88 IU/L. In the third patient, pleural fluid was straw-coloured with 1710 nucleated cells/μL, a total protein of 3.4 g/dL (protein/serum ratio of 0.52) and LDH of 149 IU/L; the patient had a moderate pericardial effusion without echocardiographic evidence of tamponade. In all reports the pleural effusions and fever resolved within 2 weeks following discontinuation of therapy. When re-challenged with the drug, the pleural effusion recurred but resolved with drug cessation.
Clozapine, ziprasidone, and sertindole-induced morphological changes in the rat heart and their relationship to antioxidant enzymes function
Published in Journal of Toxicology and Environmental Health, Part A, 2018
Aleksandra Nikolić-Kokić, Nikola Tatalović, Jelena Nestorov, Milica Mijović, Ana Mijusković, Marko Miler, Zorana Oreščanin-Dušić, Milan Nikolić, Verica Milošević, Duško Blagojević, Mihajlo Spasić, Čedo Miljević
Atypical antipsychotics AAP, also referred to as second-generation antipsychotics constitute, a group of pharmaceutical agents used to treat psychiatric conditions, primarily schizophrenia and schizophrenia-related disorders. However, in recent years these potent medications were also utilized for treatment of a broad range of symptoms and disorders, including bipolar disorder and depression as well as personality disorders and obsessive-compulsive disorder. Clozapine was the first AAP developed in 1958 and after 30 years of investigations and clinical trials, it was approved by the FDA (Crilly 2007). Currently, clozapine is considered to be one of the most effective antipsychotic drug for treatment-resistant schizophrenia (Leucht et al. 2009). Despite its effectiveness, clozapine usage is limited due to the risk of several potentially fatal adverse reactions including myocarditis and sudden death (Haas et al. 2007). Myocarditis was reported as clinically important complication observed in patients on clozapine therapy without preexisting cardiovascular diseases (Haas et al. 2007). In contrast to clozapine, ziprasidone, and sertindole are AAP that generally are considered as a low risk for development of myocarditis and heart failure (Ward et al. 2013). However, ziprasidone and sertindole were found to induce prolongation of QT interval and TdP in some patients (Naguy 2016; Nielsen et al. 2015a, 2015b)