* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download Chapter 16 Cholinesterase Inhibitors
Survey
Document related concepts
Drug design wikipedia , lookup
Polysubstance dependence wikipedia , lookup
Pharmacognosy wikipedia , lookup
Pharmaceutical industry wikipedia , lookup
Toxicodynamics wikipedia , lookup
Drug discovery wikipedia , lookup
Prescription costs wikipedia , lookup
Pharmacogenomics wikipedia , lookup
Psychedelic therapy wikipedia , lookup
Pharmacokinetics wikipedia , lookup
Drug interaction wikipedia , lookup
Chlorpromazine wikipedia , lookup
Neuropsychopharmacology wikipedia , lookup
Neuropharmacology wikipedia , lookup
Psychopharmacology wikipedia , lookup
Transcript
Antipsychotic Agents and Their Use in Schizophrenia 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 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 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) 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 Conventional Antipsychotic Agents I: Group Properties Classification Mechanism of action Therapeutic uses Adverse effects Physical and psychologic dependence Drug interactions Toxicity 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 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 Therapeutic Uses Schizophrenia Bipolar disorder (manic-depressive illness) Tourette’s syndrome Prevention of emesis Other applications Adverse Effects Extrapyramidal symptoms (EPS) Acute dystonia Parkinsonism Akathisia Tardive dyskinesia 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 Adverse Effects Other adverse effects (cont’d) Sedation Neuroendocrine effects Seizures Sexual dysfunction Dermatologic effects Agranulocytosis Severe dysrhythmias Physical and Psychologic Dependence Development of physical and psychologic dependence is rare Abrupt withdrawal of antipsychotics can precipitate a mild abstinence syndrome 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 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 Conventional Antipsychotic Agents II: Individual Agents Low-potency agents Medium-potency agents High-potency agents Depot preparations Low-Potency Agents Chlorpromazine (Thorazine) Therapeutic uses Pharmacokinetics Adverse effects Drug interactions Preparations, dosage, and administration • Oral therapy • Parenteral therapy Thioridazine (Mellaril) Medium-Potency Agents Loxapine (Loxitane) Molindone (Moban) Perphenazine (Trilafon) High-Potency Agents Haloperidol (Haldol) Actions and uses Pharmacokinetics Adverse effects Preparations, dosage, and administration • Oral therapy • Intramuscular therapy Other High-Potency Agents Fluphenazine (Prolixin) Trifluoperazine (Stelazine) Thiothixene (Navane) Pimozide (Orap) 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 Clozapine Mechanism of action Therapeutic use Blocks dopamine and serotonin Schizophrenia Levodopa-induced psychosis Pharmacokinetics 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 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 Other Atypical Antipsychotics Olanzapine (Zyprexa) Mechanism of action • Blocks 5-HT2 receptors • Blocks D2 receptors Pharmacokinetics Therapeutic uses • Schizophrenia • Bipolar disorder Adverse effects Other Atypical Antipsychotics Olanzapine (Zyprexa) (cont’d) Preparations, dosage, and administration • Schizophrenia dosage Oral dosage Oral formulation • Bipolar disorder dosage Other Atypical Antipsychotics Quetiapine (Seroquel) Actions and uses Pharmacokinetics Adverse effects Drug interactions Preparations, dosage, and administration • Schizophrenia dosage • Bipolar disorder dosage 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) 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 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) 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 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 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 Schizophrenia Drug Therapy Initial therapy Maintenance therapy Adjunctive drugs Benzodiazepines Antidepressants 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 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 Schizophrenia Nondrug Therapy Counseling for patient and family Behavioral therapy Vocational training