Antipsychotic (Neuroleptic) Drugs Course Coordinator Jamaluddin Shaikh, Ph.D. School of Pharmacy, University of Nizwa Lecture-27 April 16, 2012

Psychosis Psychosis is a mental disorders characterized by one or more of the following symptoms: diminished and distorted capacity to process information and draw logical conclusions hallucinations, delusions, or marked loosening of associations aggression or violence

Antipsychotic Drugs Antipsychotic drugs lessen psychosis Prescribed for the treatment of mania, some movement disorders, and various types of nonspecific agitated behaviors However, most frequently employed in the therapy of schizophrenia Mania: state of abnormally elevated or irritable mood Agitated behaviors:

Schizophrenia A group of disorders marked by impaired behavioral function, and disturbances of thinking Characterized by delusions, hallucinations, and thinking or speech disturbances Often initially affects people during late adolescence or early adulthood and is a chronic and disabling disorder It has a strong genetic component and probably reflects some fundamental biochemical abnormality Delusions: psychiatric condition, false belief Hallucinations: a perception in the absence of stimulus

Types of Antipsychotic Drugs Classification of antipsychotic drugs are: 1. Classical 'typical' antipsychotics chlorpromazine, haloperidol 2. Recent 'atypical' antipsychotics clozapine, risperidone

Antipsychotic Drugs: Mechanism of Action Antagonists at dopamine D2 receptors, also block other monoamine receptors, especially 5-HT2 Antipsychotic potency generally runs parallel to activity on D2-receptors, but other activities may determine side-effect profile Antipsychotics take days or weeks to work, suggesting that secondary effects may be more important than direct effect of D2-receptor block

Antipsychotic Drugs: Mechanism of Action EPS:The extrapyramidal system can be affected in a number of ways, which are revealed in a range of extrapyramidal symptoms (EPS), such as akinesia (inability to initiate movement) and akathisia (inability to remain motionless).

Relative Action on Various Receptors Chlorpromazine Haloperidol Clozapine Risperidone DA +++ ++++ ++ alpha Muscarinic 5-HT Histamine

Antipsychotic Drugs: Pharmacokinetics After oral administration, the neuroleptics show variable absorption Readily pass into the brain Have a large volume of distribution Bind well to plasma proteins Metabolized by the cytochrome P450 system in the liver Antipsychotic Drugs: Adverse Effects Side-effects include extrapyramidal motor disturbances and endocrine disturbances Sedation, dry mouth, blurred vision, hypotension are also common