Chapter 48

1. Chapter 48 Antipsychotics

2. Drug Overview • First Generation • Phenothiazines • Aliphatic: chlorpromazine • piperazine: fluphenazine, prochlorperazine, others • piperidine: mesoridazine, thioridazine • Thioxanthenes: thiothixene • Phenylbutylpiperadines • butyrophenone: haloperidol

3. Drug Overview • Second Generation • Dibenzepins • Dibenzodiazepines: clozapine, risperidone • Benzisoxazoles • Thienobenzodiazepines: olanzapine • Dibenzothiazepines: quetiapine, ziprasidone • Quinolinones • Dopamine system stabilizer: aripiprazole

4. Indications • Management of psychotic disorders • Antiemetic • Management of bipolar disorders, conduct disorders, tetanus • Generalized anxiety disorder • Depression • Tourette’s syndrome • Schizoaffective disorder • Psychosis • Mania

5. Indications • Psychiatrists Usually Treat Psychosis • PCPs See Patients with Other Medical Problems and Must Be Familiar with Antipsychotic Agents • These Drugs Are Commonly Used in Geriatrics

6. Mechanism of Action • Exact Mechanism Unknown • Thought to Work by Blocking Postsynaptic Dopamine Receptors in Various Areas of the Brain • Slow Down the Thought Processes So the Patient May Regain Reality Without Changing Intellectual Functioning • See Table 48-4

7. Mechanism of Action • First Generation • Potent antagonists of D2-dopamine receptors, more than D1 receptors • Effects on cholinergic, α1-adrenergic, and histamine receptors • Classified as high or low potency • High potency • Low potency

8. Mechanism of Action • Second Generation • Bind dopamine, including D1, D2, D4, and D5 receptors, with selectivity for limbic dopamine receptors • Increased affinity for serotonin receptors compared with D2 receptors • Bind acetylcholine at α-adrenergic receptors and muscarinic, histamine H1, and nicotinic receptors • Decreased ability to induce EPS • Increased incidence of hyperglycemia, obesity, and DM in patients taking second-generation drugs • Especially olanzapine

9. Treatment Principles • Standardized Guidelines • Veterans Administration guidelines for management of persons with psychoses • Evidence-Based Recommendations • Psychosis: Antipsychotic medications are effective for acute schizophrenia and schizoaffective disorder • Second-generation medications have a lower incidence of EPS and are preferred

10. Treatment Principles • Evidence-Based Recommendations (cont’d) • Clozapine is more effective than other agents for aggressive behaviors and management of suicidality • Black box warning for leukopenia • Dementia: Olanzapine and risperidone show modest evidence for efficacy; associated with increased risk of cardiovascular events, including stroke and TIA

11. Treatment Principles • Cardinal Points of Treatment • Psychosis • Typical and atypical antipsychotic agents equally efficacious • Atypicals generally preferred first line for long-term treatment • Patient response is individualized • Response or lack of response to one drug does not predict the response of another drug • Therapeutic effect is measured by the patient’s increase in functional abilities and decrease in psychotic symptoms

12. Treatment Principles • Cardinal Points of Treatment • Psychosis (cont’d) • Generally takes 3 weeks to achieve full therapeutic benefit • Initially responsive patients may relapse • Dosage is gradually increased to achieve therapeutic effect while minimizing side effects • Once therapeutic effect is reached, decrease dosage for long-term maintenance • Drug holidays are not recommended

13. Treatment Principles • Cardinal Points of Treatment • Psychosis (cont’d) • Formulation is determined by the patient’s willingness to take the medication • First-generation antipsychotics tend to have a greater effect on decreasing positive symptoms • Second-generation medications may be more effective against negative symptoms

14. Treatment Principles • Cardinal Points of Treatment (cont’d) • Symptom management in geriatric patients • American Psychiatric Association guidelines • Nonpharmacologic management is initial approach • Use of psychotropics in geriatric dementia is common practice, but they do not have FDA approval for this use • Risperidone and olanzapine increased risk of development of heart disease and stroke

15. Treatment Principles • Cardinal Points of Treatment • Symptom management in geriatric patients (cont’d) • Psychotropics are useful in treating symptoms of dementia • Agitation • Hyperactivity • Hallucination • Suspiciousness • Hostility • Uncooperativeness

16. Treatment Principles • Cardinal Points of Treatment • Symptom management in geriatric patients (cont’d) • Antipsychotics are used for the long-term management of behavioral/psychologic symptoms of dementia and delirium resistant to behavioral therapy

17. How to Monitor • General • LFTs, CBC, cholesterol • clozapine • Weekly CBC with differential • Assess for Extrapyramidal Symptoms at Each Encounter • Monitor Blood Glucose Monthly for Onset of DM • Follow Weight

18. Patient Variables • Geriatrics • Pediatrics • Pregnancy and Lactation • Race • Gender

19. Patient Education • Hypotension • Drowsiness • Risk of EPS and Irreversible TD • Photosensitivity • Dry Mouth • Smoking • Alcohol • Missed Doses • Take with Food • Avoid Antacids Within 1 Hour of Dose

20. chlorpromazine (Thorazine) • Contraindications • Warnings • Precautions • Pharmacokinetics • Adverse Effects • Drug Interactions • Overdosage

21. clozapine (Clozaril) • Indications • Contraindications • Warnings

22. risperidone (Risperdal) • Contraindications • Warnings • Precautions • Adverse Effects • Drug Interactions