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  • Depending on chemical class, neuroleptics cause varying degrees of CNS depression, anticholinergic symptoms, cardiac toxicity, and movement abnormalities.
  • Movement disturbances, known as extrapyramidal symptoms (EPS), include acute dystonic reactions, Parkinson dyskinesias, akathisia, and tardive dyskinesia. Many EPS reactions respond to administration of an anticholinergic agent such as diphenhydramine or benztropine mesylate.
  • Cardiac conduction disturbances, most notably a prolonged QT interval, are significant complications associated with thioridazine and haloperidol.
  • Neuroleptic malignant syndrome (NMS) is a life-threatening condition associated with chronic medication therapy and acute drug overdose characterized by hyperthermia, skeletal muscle rigidity, and altered mental status.
  • Newer “atypical neuroleptics” offer therapeutic advantages of lowered incidences of EPS and NMS. Toxicity from these agents may include blood dyscrasias, CNS and respiratory depression, hypotension, and reflex tachycardia.

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Neuroleptics or phenothiazines are a group of major tranquilizers or antipsychotic drugs that are designed to treat schizophrenia and other psychiatric disorders.

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There are several classes of typical neuroleptics (Table 118–1),1 all of which have the same basic three-ringed structure. Although all classes exhibit similar therapeutic and adverse effects, modification of the basic structure results in variable degrees of toxicity.2 Neuroleptics include broadly diverse chemical classes. These entities differ in the degree to which they cause anticholinergic, cardiovascular, or EPS reactions.

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Table Graphic Jump Location
Table 118-1. Common Typical Neuroleptics 
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Neuroleptics act by blocking dopaminergic, α-adrenergic, muscarinic, histaminic, and serotonergic neuroreceptors. Blockade of the dopamine receptors results in the desired behavior modification, but also produces extrapyramidal side effects, such as dystonic reactions. α-adrenergic blockade produces peripheral vasodilation and orthostatic hypotension. Muscarinic blockade results in anticholinergic properties such as sedation, tachycardia, flushed or dry skin, urinary retention, and delayed GI motility. Neuroleptics also cause a membrane-depressant action or quinidinelike effect that alters myocardial contractility, and can result in conduction defects. Although the mechanism of toxicity in neuroleptics resembles that of tricyclic antidepressants, serious cardiac dysrhythmias, refractory hypotension, respiratory depression, and seizures are uncommon.3

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Clinical Presentation

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Acute dystonia is an unpredictable side effect of neuroleptics that occurs in approximately 10% of overdoses. It can also occur as an idiosyncratic reaction following a single therapeutic dose of a neuroleptic. Dystonic reactions are characterized by slurred speech, dysarthria, confusion, dysphagia, hypertonicity, tremors, and muscle restlessness. Other reactions or dyskinesias include oculogyric crisis (upward gaze), torticollis (neck twisting), facial grimacing, opisthotonos, and tortipelvic gait disturbances. Symptoms usually begin within the first 5 to 30 hours after ingestion. Dystonic reactions are relatively common in infants and adolescents.

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Of the neuroleptics, prochlorperazine most often ...

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