1. Antipsychotic Drugs-Lecture Objectives Classifications of mental illness Schizophrenias (Functional psychoses & neuropathologies) Schizophreniform illness-Types I & II Antipsychotic drugs(classification, mechanism of action, pharmacological actions, uses & side effects)

2. Lecture 48-Antipsychotic Drugs-Lecture Outcomes At the end of this lecture, you should be able to: –Classify mental illness –Identify Schizophrenias as Functional psychoses & recognize the neuropathologies –Explain Schizophreniform illness-Types I & II –Classify Antipsychotic drugs & discuss the mechanism of action, pharmacological actions, uses & side effects of antipsychotic drugs

3. Psychoses-Thought Disorders Psychoses: –Mental disorders characterized by: Positive symptoms Negative symptoms –Hallucinations –Delusions

4. Antipsychotics-Overview Used in the treatment of psychoses: –Acute, & –Chronic Improve mood + behavior No excessive sedation Reversible/irreversible extrapyramidal symptoms (EPS)

5. Antipsychotics-Classification Phenothiazines –Aliphatic- Chlorpromazine –Piperidine- Mesoridazine –Piperazine- Fluphenazine Thioxanthines –Chlorprothixene Butyrophenones –Haloperidol

6. Antipsychotics-Classification (contd.) Dibenzodiazepines –Clozapine Dibenzoxazepine –Loxapine succinate Dihydroindolones –Molindone Benzisoxazole compounds –Risperidone Miscellaneous

7. Low & High-Potency Antipsychotics /Neuroleptics Low Potency Antipsychotics/Neuroleptics (Low propensity for EPS) –Phenothiazines(Aliphatic & Piperidine types) High Potency Antipsychotics/Neuroleptics (High propensity for EPS) –Phenothiazines(Piperazine type) –Butyrophenone(Haloperidol)

8. Antipsychotics-Mechanism of Action Classical/Typical Antipsychotic/neuroleptic action due to D2 receptor blockade in mesolimbic system Clozapine(Atypical Antipsychotic) blocks D4 receptors

9. Antipsychotics- Pharmacological Actions CNS Actions –↓ Hallucinations/ ↓ Delusions –Long-term treatment→Behavioural Improvement –Neuroleptic Effect

10. Antipsychotics- Pharmacological Actions(contd.) CNS Actions(contd.) –Antiemetic Action D-receptor blockade in CTZ ↑↑PTZ doses→↓VC in medulla oblongata –Alter temperature-regulating mechanism ↓ body temperature(hypothermia) ↑

11. Antipsychotics- Pharmacological Actions(contd.) Endocrine Alterations –PTZs→↓D2-receptors(in pituitary) ↓PRIH(Dopamine) action ↑ Prolactin release Galactorrhea-Amenorrhea Syndrome

12. Antipsychotics- Pharmacological Actions(contd.) Endocrine Alterations(contd.) –PTZs→↓GH release/↓ACTH release –PTZs → Abnormal Pigmentaton PTZs→↑Appetite/Weight Gain

13. Antipsychotics- Pharmacological Actions(contd.) Peripheral Actions –Anticholinergic Actions –Alpha-adrenergic blocking activity→Miosis –CPZ→potent local anesthetic –Orthostatic hypotension

14. Antipsychotics- Pharmacological Actions(contd.) Peripheral Actions(contd.) –CPZ→ ↓ ADH secretion →weak diuresis –PTZs→H1 receptor blockade –PTZs→ ↑↑ actions of Ethanol/Barbiturates/ Narcotics

15. Antipsychotics-Therapeutic Uses Psychotic disorders –Mania/Paranoid states/Schizophrenia/Psychoses associated with chronic alcoholism Prevention/Treatment of nausea & vomiting(e.g.,drug- induced) Agitated depression –Neuroleptics→tranquillize patients(acute agitation/ disruptive behaviour) Intractable hiccup→CPZ Gilles de la Tourette’s Syndrome –Haloperidol/Pimozide

16. Antipsychotics-Adverse Effects Parkinsonian effects(Iatrogenic EPS) –↓Dopaminergic = ↑Cholinergic –Neuroleptics→block dopamine receptors →↑↑cholinergic dominance→EPS –Benzhexol(Trihexyphenidyl)/Benztropine –Typical Neuroleptics with anticholinergic activity e.g., Mesoridazine/Thioridazine( ↓↓ incidence of EPS)

17. Antipsychotics-Adverse Effects (contd.) Parkinsonian effects(contd.) –Use atypical neuroleptics e.g., Clozapine/Risperidone/Sulpiride/Remoxipride/ Quetiapine/Sertindole/Olanzapine Tardive Dyskinesia –Long-term neuroleptic treatment→prolonged dopaminergic blockade→up-regulation of dopamine receptors→dyskinesias –Diazepam/Reserpine/Li +

18. Antipsychotics-Adverse Effects (contd.) CNS Depression –Drowsiness/Confusion Anticholinergic –Dry mouth/Urinary retention/Constipation Others –Orthostatic hypotension(CPZ)/Jaundice/ Endocrine alterations/Cardiac Arrhythmias/ Seizures(Clozapine)

19. Antipsychotics-Adverse Effects (contd.) Neuroleptic Malignant Syndrome –Life-threatening idiosyncratic reaction –Due to excessively rapid post-synaptic D2- receptor blockade(in hypothalamus/midbrain) –Risk is higher when high-potency neuroleptic agents are used in high doses, especially if given parenterally –Mortality from NMS is greater than 10%

20. Antipsychotics-Adverse Effects (contd.) Neuroleptic Malignant Syndrome(contd.) –Treatment Dantrolene Na Bromoergocryptine Anticholinergics Muscle relaxants Fever(cooling by physical measures)

21. Antipsychotics-Cautions & Contraindications Acute agitation due to alcohol withdrawal –Neuroleptics aggravate –Treatment-Benzodiazepines(e.g., Lorazepam)/Clonidine Cardiac Arrhythmias PTZ’s→↓seizure threshold→Epilepsy