Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Pharmacogenomics wikipedia , lookup
Psychedelic therapy wikipedia , lookup
Pharmacokinetics wikipedia , lookup
Drug interaction wikipedia , lookup
Neuropsychopharmacology wikipedia , lookup
Neuropharmacology wikipedia , lookup
Psychopharmacology wikipedia , lookup
Chapter 31 Antipsychotic Agents and Their Use in Schizophrenia Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Antipsychotic Agents Chemically diverse group of compounds Used for diverse spectrum of psychotic disorders Schizophrenia, delusional disorders, bipolar disorders, depressive psychoses, drug-induced psychoses Also used to suppress emesis and to treat Tourette’s syndrome and Huntington’s chorea Should not be used to treat dementia in the older adult Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 2 Antipsychotic Agents First-generation antipsychotics (FGAs) or conventional antipsychotics Block receptors for dopamine in CNS Cause serious movement disorders (extrapyramidal symptoms [EPS]) Second-generation antipsychotics (SGAs) or atypical antipsychotics Produce only moderate blockade of dopamine receptors; stronger blockade for serotonin Fewer EPS Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 3 Antipsychotic Agents Top-selling medications in the United States in 2009 Total sales of $14.6 billion FGA higher risk of EPS SGA higher risk of metabolic effects (diabetes, dyslipidemia) Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 4 Clinical Presentation Disordered thinking and reduced ability to comprehend reality Three types of symptoms Positive symptoms and negative symptoms Cognitive symptoms Acute episodes Residual symptoms Long-term course Causes Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 5 Conventional Antipsychotic Agents I: Group Properties Classification Mechanism of action Therapeutic uses Adverse effects Physical and psychologic dependence Drug interactions Toxicity Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 6 Classification Classification by potency Low potency: chlorpromazine HCl (Thorazine) Medium potency: loxapine (Loxitane) High potency: haloperidol (Haldol) Chemical classification Six major chemical categories Drugs in all groups equivalent with respect to antipsychotic actions Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 7 Mechanism of Action Conventional antipsychotic drugs block a variety of receptors within and outside the CNS They block dopamine2 (D2) receptors in the mesolimbic area of the brain Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 8 Therapeutic Uses Schizophrenia Bipolar disorder (manic-depressive illness) Tourette’s syndrome Prevention of emesis Other applications Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 9 Adverse Effects Extrapyramidal symptoms (EPS) Acute dystonia Parkinsonism Akathisia Tardive dyskinesia Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 10 Adverse Effects Other adverse effects Neuroleptic malignant syndrome • Rare but serious reaction • Risk of death without treatment • Sweating, rigidity, sudden high fever, autonomic instability Anticholinergic effects • See Table 31-3. Orthostatic hypotension Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 11 Adverse Effects Other adverse effects (cont’d) Sedation Neuroendocrine effects Seizures Sexual dysfunction Dermatologic effects Agranulocytosis Severe dysrhythmias Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 12 Physical and Psychologic Dependence Development of physical and psychologic dependence is rare Abrupt withdrawal of antipsychotics can precipitate a mild abstinence syndrome Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 13 Drug Interactions Anticholinergic drugs CNS depressants Intensify the anticholinergic effect Can intensify the depressant effect Levodopa and direct dopamine receptor agonists May counteract the antipsychotic effects of neuroleptics Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 14 Toxicity Conventional antipsychotic drugs are very safe Death by overdose is extremely rare Overdose produces hypertension, CNS depression, and EPS Treatment Intravenous fluids, alpha-adrenergic agonist, gastric lavage Emetics not effective: neuroleptics block the antiemetic action Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 15 Conventional Antipsychotic Agents II: Individual Agents Low-potency agents Medium-potency agents High-potency agents Depot preparations Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 16 Low-Potency Agents Chlorpromazine (Thorazine) Therapeutic uses Pharmacokinetics Adverse effects Drug interactions Preparations, dosage, and administration • Oral therapy • Parenteral therapy Thioridazine (Mellaril) Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 17 Medium-Potency Agents Loxapine (Loxitane) Molindone (Moban) Perphenazine (Trilafon) Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 18 High-Potency Agents Haloperidol (Haldol) Actions and uses Pharmacokinetics Adverse effects Preparations, dosage, and administration • Oral therapy • Intramuscular therapy Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 19 Other High-Potency Agents Fluphenazine (Prolixin) Trifluoperazine (Stelazine) Thiothixene (Navane) Pimozide (Orap) Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 20 Atypical Antipsychotic Agents Introduced in the 1990s Less risk of EPS than FGAs Increased risk of weight gain, diabetes, and dyslipidemia Examples: clozapine and other atypical antipsychotics Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 21 Clozapine Mechanism of action Therapeutic use Blocks dopamine and serotonin Schizophrenia Levodopa-induced psychosis Pharmacokinetics Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 22 Clozapine Adverse effects and interactions Agranulocytosis Seizures Diabetes Weight gain Myocarditis Effects in older adult patients with dementia • About double the mortality rate Drug interactions Preparations, dosage, and administration Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 23 Other Atypical Antipsychotics Risperidone (Risperdal) Mechanism of action • Binds to multiple receptors Pharmacokinetics Therapeutic effects Adverse effects • Generally infrequent and mild Preparations, dosage, and administration • Schizophrenia, oral therapy • Schizophrenia, intramuscular therapy • Bipolar disorder Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 24 Other Atypical Antipsychotics Olanzapine (Zyprexa) Mechanism of action • Blocks 5-HT2 receptors • Blocks D2 receptors Pharmacokinetics Therapeutic uses • Schizophrenia • Bipolar disorder Adverse effects Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 25 Other Atypical Antipsychotics Olanzapine (Zyprexa) (cont’d) Preparations, dosage, and administration • Schizophrenia dosage Oral dosage Oral formulation • Bipolar disorder dosage Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 26 Other Atypical Antipsychotics Quetiapine (Seroquel) Actions and uses Pharmacokinetics Adverse effects Drug interactions Preparations, dosage, and administration • Schizophrenia dosage • Bipolar disorder dosage Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 27 Other Atypical Antipsychotics Ziprasidone (Geodon) Mechanism of action • Blocks multiple receptors: D2, 5-HT2, H1 Pharmacokinetics Adverse effects Drug interactions Preparations, dosage, and administration • Schizophrenia, intramuscular dosage • Bipolar disorder (see Table 31-4) Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 28 Other Atypical Antipsychotics Aripiprazole (Abilify) Contrasts with other atypical antipsychotic agents Mechanism of action • Blocks multiple receptor types Pharmacokinetics Adverse effects Drug interactions Preparations, dosage, and administration • Schizophrenia dosage • Bipolar disorder dosage Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 29 Depot Preparations Depot antipsychotics: long-acting, injectable formulations used for long-term maintenance therapy of schizophrenia No evidence that depot preparations pose an increased risk of side effects Three depot preparations available Haloperidol decanoate (Haldol Decanoate) Fluphenazine decanoate (Prolixin Decanoate) Risperidone microspheres (Risperdal Consta) Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 30 Schizophrenia Drug Therapy Three major objectives Suppression of acute episodes Prevention of acute exacerbations Maintenance of the highest possible level of functioning Drug selection Dosing Route Oral (tablets, capsules, liquids) Intramuscular Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 31 Schizophrenia Drug Therapy Most FGAs and SGAs are equally effective, except for clozapine, which is more effective than the rest FGAs: significant risk of EPS SGAs: risk of metabolic effects FGAs: cost 10 times less than SGAs Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 32 Schizophrenia Drug Therapy Dosing Highly individualized Older adult patients require relatively small doses. Size and timing likely to be changed over course of therapy Routes Oral (preferred) Intramuscular Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 33 Schizophrenia Drug Therapy Initial therapy Maintenance therapy Adjunctive drugs Benzodiazepines Antidepressants Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 34 Schizophrenia Drug Therapy Promoting adherence Ensure that the medication is taken Encourage family members to oversee medication for outpatients Provide patients with instructions Inform patients and their families that antipsychotics must be taken on a regular schedule Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 35 Schizophrenia Drug Therapy Promoting adherence (cont’d) Inform patients about side effects of treatment Assure patients that antipsychotic drug use does not lead to addiction Establish a good therapeutic relationship with patient Use an intramuscular depot preparation for longterm therapy Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 36 Schizophrenia Nondrug Therapy Counseling for patient and family Behavioral therapy Vocational training Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 37