ANTIPSYCHOTIC DRUGS Dr MEHERUNISA ASSOCIATE PROFESSOR PHARMACOLOGY CIMS

ANTI-PSYCHOTIC DRUGS Dr MEHERUNISA ASSOCIATE PROFESSOR PHARMACOLOGY CIMS

CASE SCENARIO A 45 year old male patient was brought to the casualty in agitated state. His wife complains that he is agitated, talkative and keeps on mumbling to himself and does not sleep well at night. When asked about his mumbling, he says that his wife and children are trying to poison him. He has been talking to his mother about this & believes that only she can save him. ( according to his wife , the mother passed away 20 yrs ago)

Family h/o father & mother not alive. 3 siblings. One brother is admitted to mental asylum. others normal. 2 children - both normal. Past h/o he had similar symptoms and was on treatment, but discontinued as soon as his symptoms disappeared. O/E—Well built, but poorly nourished. Poor hygiene. Weight- 50 kg. He is anxious, worried and suspicious of the interviewer. He is well oriented, but keeps on talking to himself. All systems within normal limits. Biochemical parameters – normal, ECG- normal

1) What is your diagnosis? Schizophrenia- paranoid (DSM-V-TR) DSM-V-TR Diagnostic Criteria for Schizophrenia Two (or more) of the following, each present for a significant portion of time during a 1 -month period delusions hallucinations disorganized speech grossly disorganized or catatonic behaviour negative symptoms, i. e. , affective flattening, alogia, avolition, anhedonia

Treatment was started and within 2 weeks he became less agitated and started taking interest in himself & surroundings & became more cooperative. Sleeps well at night. After 4 weeks of treatment, he began to socialise with his family and neighbours but still continues to have auditory hallucinations. Adequate dose adjustment was done. After 6 months of treatment , all his symptoms subsided. O/E – adequately nourished. Wt 63 kg. Very co-operative. Answering to all questions. Biochemistry : RBS- 180 mg %. Urine sugar +ve others –normal, ECG – normal

PSYCHIATRIC DISORDERS 2 Types - PSYCHOSIS / NEUROSIS PSYCHOSIS - Insight is absent Refuses to take treatment Schizophrenia & Mood disorders… NEUROSIS – Less serious , insight is present Anxiety, OCD, PTSD, Phobias …

2) Name the older /classical /typical /1 st generation antipsychotics. (NEUROLEPTICS) A) Phenothiazines Chlorpromazine Triflupromazine Thioridazine Mesoridazine Fluphenazine Perphenazine Trifluoperazine Aliphatic derivatives Piperidene derivatives Piperazine derivatives

B) Thioxanthenes Thiothixene Chlorprothixene Flupenthixol C) Butyrophenone Derivatives Haloperidol Droperidol Penfluridol D) Others Pimozide , Loxapine, Molindone

Clinical classification Low potent: eg. Chlorpromazine, Thioridazine Mid potent: eg. Trifluperazine, Perphenazine High potent: eg. Haloperidol, Fluphenazine, Thiothixene

3) Atypical / 2 nd generation antipsychotics Clozapine Olanzapine Risperidone Quetiapine Aripiprazole Ziprasidone Lurasidone Paliperidone Iloperidone Sertindole Asenapine Zotepin Amisulpride

4. How will you treat his present agitated state? Treatment during the acute phase focuses on alleviating the most severe psychotic symptoms. This phase usually lasts from 4 to 8 weeks. Antipsychotics and benzodiazepines can result in relatively rapid calming of patients. � Haloperidol � Fluphenazine � Olanzapine � Ziprasidone Less EPS

BZD Lorazepam (Ativan) has the advantage of reliable absorption when it is administered either orally or intramuscularly. The use of benzodiazepines may also reduce the amount of antipsychotic that is needed to control psychotic patients.

5) Name a drug that can be used immediately to control his symptoms. Mention its route and onset of action? Parenteral short acting drugs Haloperidol- 5 -10 mg intramuscular Onset of action- 30 -60 mts repeated at 4 -8 hrs for the first 24 -72 hrs. Other drugs- fluphenazine olanzapine ziprasidone Other option- BZD

6) Will you use injectable long acting depot preparation to control his symptoms in acute phase? Why? NO take months to reach a steady-state concentration and are eliminated very slowly difficult to correlate clinical effect with dosage, and it is extremely difficult to make dosage adjustments to manage side effects.

7) Name the drugs which are available as long acting preparations. Mention its indications? Fluphenazine Haloperidol Risperidone long-acting decanoate injections

8) Once his agitation & other symptoms are controlled, which drug can we use to stabilize him? Any atypical agent to control symptoms acute stage stabilization stage stable stage

9) How long should you continue the treatment for stabilisation? 6 months

10) How does this drug act? Dopamine Psychosis Mesolimbic-mesocortical- behaviour, cognition Nigrostriatal- vol movement coordination Tuberoinfundibular – suppresses prolactin secretion Medullary periventricular – eating Incertohypothalamic – copulatory behaviour D 2, 5 HT 2 A, D 4, D 1 - Antagonism

11) What are its adverse effects? 1. Cardiovascular 2. Cerebrovascular 3. Neurological – EPS 4. Metabolic 5. Blood 6. Skin eruptions 7. Ocular 8. GI & hepatic S/E

12) What is meant by SDA? Serotonin Dopamine Antagonist- second generation antipsychotics.

13) Comment on the efficacy and potency of antipsychotics. Efficacy Positive symptoms- new drugs equal to old drugs Negative symptoms- newer ones are superior Potency high (e. g. , haloperidol) low (e. g. , chlorpromazine), intermediate (e. g. , loxapine) affinity for D 2 receptor

14) What are the extrapyramidal side effects likely to occur?

REACTION FEATURES Acute dystonia Spasm of muscles of tongue, face, neck, back; may mimic seizures; not hysteria Akathisia Motor restlessness; not anxiety or "agitation" Parkinsonism Bradykinesia, rigidity, variable tremor, mask facies, shuffling gait Catatonia, stupor, fever, unstable blood pressure, Neuroleptic malignant syndrome Perioral tremor ("rabbit TIME OF MAXIMALTREATMENT RISK 1 to 5 days Antiparkinsonian agents are diagnostic and curative 5 to 60 days Reduce dose or change drug; antiparkinsonian agents, a benzodiazepines or propranolol b may help 5 to 30 days; can Antiparkinsonian agents recur even after a helpfula single dose Weeks; can persist Stop neuroleptic for days after immediately; dantrolene or myoglobinemia; can be stopping bromocriptine c may help; fatal neuroleptic antiparkinsonian agents not effective Perioral tremor (may be a After months or Antiparkinsonian agents late variant of years of treatment often helpa

15) What are the antipsychotics C/I in patients with heart disease? Prolonged QT interval- 1. Thioridazine 2. Pimozide 3. High doses of haloperidol 4. Ziprasidone Myocarditis & cardiomyopathy clozapine

16) What are the metabolic adverse effects likely to occur with antipsychotics? 1. Weight gain- max- clozapine & olanzapine Risperidone produces intermediate weight gain Quetiapine and ziprasidone produce the least weight gain. 2. Hyperglycemia , hyperlipidemia, exacerbation of existing type 1 and 2 DM, new-onset type 2 DM, and diabetic ketoacidosis.

17) Name the antipsychotic causing retinopathy. Thioridazine 18) What are its other significant adverse effects? Comment on the extrapyramidal A/E produced by this drug. Low incidence of adverse EPS increased central antimuscarinic activity Depressant effects on cardiac conduction and repolarization. Impaired ejaculation- alpha blockade, anticholinergic

19) Name the antipsychotic producing hypersalivation. Why does it cause that? how will you treat it? Clozapine Muscarnic agonism at M 4 receptors. Clonidine , anticholinergics, amitriptyline, scopolamine patch, ipratropium sublingual spray , atropine 1% solution, botulinum toxin

20) Name the longest acting antipsychotic. What are its other advantages? Aripiprazole and its active metabolite – t½ 75 and 94 hrs Adv Long t ½ partial DA agonist, enhance action at these receptors when there is a low concentration of dopamine and would block the actions of high concentrations of dopamine Min weight gain Lower EPS Produces no elevation of prolactin

21) Mention the indications & contraindications of clozapine? Treatment of refractory schizophrenia. Clozapine is the first drug to be FDA approved for an antisuicide indication in schizophrenia pts.

Contraindications to clozapine H/o myeloproliferative disorder Uncontrolled epilepsy Paralytic ileus Clozapine-induced agranulocytosis or granulocytopenia with caution patients who cannot tolerate anticholinergic effects. at risk for drug-induced orthostasis. significant renal or hepatic disease.

22)How will you monitor a patient on clozapine? Monitoring of WBC count Weekly monitoring- 6 months Every 3 weeks – next 6 months Monthly there after. Monitoring of body weight, lipid profile, blood glucose level also important.

23) Name the antipsychotic with antianxiety & antidepressant action. What are its advantages and disadvantages? Ziprasidone – antianxiety & antidepressant Adv im formulation Min metabolic A/E, EPS, sedation Disadv Short t ½ Cardiac depressant action

24)Name the atypical agent preferred in autism? What are its advantage and disadvantage ? Risperidone ADV- similar to other atypical drugs, though EPS more than the other atypical drugs DISADV- hyperprolactinemia

25) Name the only antipsychotic given sublingually. Asenapine 26) Name a 1 st generation antipsychotic with metabolic side effects. ( Wt gain, Hyperglycemia, Hypertriglyceremia) Chlorpromazine

27) Other uses of antipsychotic agents The older neuroleptics (most commonly prochlorperazine) drug-induced nausea/vomiting. Intractable hiccups - Chlorpromazine. Tourette's disorder - Pimozide, Risperidone and haloperidol. Anxiety disorders (OCD, PTSD) – Quetiapine, Risperidone Huntington’s chorea Autism – Risperidone, Aripiprazole Neuroleptic anesthesia – Droperidol + Fentanyl Menon’s Lytic cocktail regime – CPZ + Pethidine +Promethazine

THANK YOU!!!