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Intro to Psychopharmacology - Part I: Antipsychotic Agents

Intro to Psychopharmacology - Part I: Antipsychotic Agents. Jack Foust, MD Assistant Professor, Psychiatry and Behavioral Sciences MUSC. Psychopharmacologic Agents. Antipsychotics Antiparkinsonian agents Antidepressants Mood stabilizers/Anti-manic agents Antianxiety agents.

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Intro to Psychopharmacology - Part I: Antipsychotic Agents

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  1. Intro to Psychopharmacology - Part I: Antipsychotic Agents • Jack Foust, MD • Assistant Professor, Psychiatry and Behavioral Sciences • MUSC

  2. Psychopharmacologic Agents • Antipsychotics • Antiparkinsonian agents • Antidepressants • Mood stabilizers/Anti-manic agents • Antianxiety agents

  3. Antipsychotics • Used to treat psychotic disorders, such as schizophrenia, mania, psychotic depression • Include both “typicals” (Haldol) and “atypicals” (Clozaril, Risperdal)

  4. Antipsychotics: Typical • Haloperidol (Haldol) • Fluphenazine (Prolixin) • Thioridazine (Mellaril) • Chlopromazine (Thorazine)

  5. Antipsychotics: Typical, cont. • Antidopaminergic • Anticholinergic • Antihistaminic • Anti-alpha 1

  6. Antipsychotics: Atypical • Clozapine (Clozaril) is prototype; also risperidone (Risperdal), olanzepine (Zyprexa) • Clinically display less EPS, may be more effective against negative symptoms • Balanced D2/D1 antagonism • Strong 5HT2 antagonists

  7. Side Effects of Typical Antipsychotics • Antidopaminergic effects • EPS, TD, hyperprolactinemia • Four dopamine pathways • Mesocortical (? negative symptoms) • Mesolimbic (antipsychotic) • Nigrostriatal (EPS, TD) • Tuberoinfundibular (hyperprolactinemia)

  8. Side Effects of Typical Antipsychotics, cont. • Anticholinergic effects • Dry mouth • Urinary retention • Constipation • Drowsiness • Tachycardia • Delirium/Cognitive dysfunction

  9. Side Effects of Typical Antipsychotics, cont. • Sedation (anti-H1) • Weight gain (anti - H1, ?anti-5Ht2c) • Seizures (?anti-5HT2c) • Transaminase elevation

  10. Tardive Dyskinesia • 25-year continuous exposure risk: 68% in Yale Incidence Study • Annual incidence: 5% • Risk factors • Increased age • African-American race • Dose and duration of drug exposure • Early and severe EPS

  11. Summary: Efficacy and Safety of Typical Antipsychotics • Limited efficacy against negative symptoms • Poor response with positive symptoms in many patients • Numerous side effects • Noncompliance

  12. Advantages of Typical Antipsychotics • No blood monitoring • Efficacious for positive symptoms • Parenteral and depot preparations available • Low-cost

  13. Atypicality - What is it? • Clozapine - prototype for new class of antipsychotics - “Atypical Antipsychotic” • Clinically - low/no EPS, TD; greater effect on negative symptoms • Neuropharmacologically - D2/D1 equivalence; increased 5HT2a antagonism

  14. Serotonin-Dopamine Antagonists and TD: Hypothesized “Site-Specific” Neuromechanisms Psychosis EPS and TD Limbic Cortical Caudate/Putamen A10 A9 Ventral Tegmental Area Substantia Nigra Dopamine/5HT Antagonist Conventional Antipsychotic Agents

  15. Newer Antipsychotics

  16. Antiparkinsonian Agents • Diphenhydramine (Benadryl) • Benztropine (Cogentin) • Trihexylphenidyl (Artane) • Amantadine (Symmetryl) - D2 Agonist

  17. Antiparkinsonian Agents • Used to relieve EPS caused by typical neuroleptics • Work through anticholinergic mechanisms to restore dopamine/acetylcholine balance in striatum (extrapyramidal motor system) - amantadine (Symmetryl) is an exception

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