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the first 2 months of treatment They subside on discontinuance of the drug There is cross-sensitivity among all of the phenothiazines, and a drug from a different group should be used when allergic reactions occur Clozapine is associated with a 16% risk of agranulocytosis (higher in persons of Ashkenazi Jewish ancestry), and its use must be strictly monitored with weekly blood counts during the first 6 months of treatment, with monitoring every other week thereafter Discontinuation of the medication requires weekly monitoring of the white blood cell count for 1 month Recently, clozapine has been associated with fatal myocarditis and is contraindicated in patients with severe heart disease In addition, clozapine lowers the seizure threshold and has many side effects, including sedation, hypotension, increased liver enzyme levels, hypersalivation, respiratory arrest, weight gain, and changes in both the ECG and the EEG Photosensitivity, retinopathy, and hyperpigmentation are associated with use of fairly high dosages of chlorpromazine and thioridazine The appearance of particulate melanin deposits in the lens of the eye is related to the total dose given, and patients on long-term medication should have periodic eye examinations Teratogenicity has not been causally related to these drugs, but prudence is indicated particularly in the first trimester of pregnancy The seizure threshold is lowered, but it is safe to use these medications in epileptics who take anticonvulsants The neuroleptic malignant syndrome (NMS) is a catatonia-like state manifested by extrapyramidal signs, blood pressure changes, altered consciousness, and hyperpyrexia; it is an uncommon but serious complication of neuroleptic treatment Muscle rigidity, involuntary movements, confusion, dysarthria, and dysphagia are accompanied by pallor, cardiovascular instability, fever, pulmonary congestion, and diaphoresis and may result in stupor, coma, and death The cause may be related to a number of factors, including poor dosage control of neuroleptic medication, affective illness, decreased serum iron, dehydration, and increased sensitivity of dopamine receptor sites Lithium in combination with a neuroleptic drug may increase vulnerability, which is already increased in patients with an affective disorder In most cases, the symptoms develop within the first 2 weeks of antipsychotic drug treatment The syndrome may occur with small doses of the drugs Intramuscular administration is a risk factor Elevated creatine kinase and leukocytosis with a shift to the left.
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QTc prolongation is a side effect of many medications and suggests a possible risk for arrhythmia Among atypical neuroleptics, only ziprasidone carries a special warning regarding the risk of QTc prolongation Adapted, with permission, from American Diabetes Association: Consensus Development Conference on Antipsychotic Drugs and Obesity and Diabetes Diabetes Care 2004 Feb;27(2):596 601
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