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Anti psychotic drugs

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Anti psychotic drugs

  1. 1. ANTI-PSYCHOTIC DRUGS Dr.RENJU.S.RAVI
  2. 2. 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)
  3. 3.  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
  4. 4.  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
  5. 5.  Treatment was started and within 2 weeks he became less agitated and started taking interest in himself & surroundings & became more co- operative. 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
  6. 6. 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 …
  7. 7.  2) Name the older /classical /typical /1st generation antipsychotics. (NEUROLEPTICS)  A) Phenothiazines  Chlorpromazine  Triflupromazine  Thioridazine  Mesoridazine  Fluphenazine  Perphenazine  Trifluoperazine Aliphatic derivatives Piperazine derivatives Piperidene derivatives
  8. 8.  B) Thioxanthenes  Thiothixene  Chlorprothixene  Flupenthixol  C) Butyrophenone Derivatives  Haloperidol  Droperidol  Penfluridol D) Others  Pimozide ,Loxapine, Molindone
  9. 9. Clinical classification  Low potent: eg .Chlorpromazine, Thioridazine  Mid potent: eg. Trifluperazine, Perphenazine  High potent: eg .Haloperidol, Fluphenazine, Thiothixene
  10. 10.  3) Atypical / 2nd generation antipsychotics  Clozapine  Olanzapine  Risperidone  Quetiapine  Aripiprazole  Ziprasidone  Lurasidone  Paliperidone  Iloperidone  Sertindole  Asenapine  Zotepin  Amisulpride
  11. 11. 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
  12. 12. 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.
  13. 13. 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
  14. 14.  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.
  15. 15.  7) Name the drugs which are available as long acting preparations. Mention its indications?  Fluphenazine  Haloperidol long-acting decanoate injections  Risperidone
  16. 16.  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
  17. 17.  9) How long should you continue the treatment for stabilisation?  6 months
  18. 18. 10) How does this drug act?  Mesolimbic-mesocortical- behaviour, cognition  Nigrostriatal- vol movement coordination  Tuberoinfundibular – suppresses prolactin secretion  Medullary periventricular – eating  Incertohypothalamic – copulatory behaviour  D2, 5HT2A,D4,D1 - Antagonism Dopamine Psychosis
  19. 19.  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
  20. 20.  12) What is meant by SDA?  Serotonin Dopamine Antagonist- second generation antipsychotics.
  21. 21. 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 D2 receptor
  22. 22.  14) What are the extrapyramidal side effects likely to occur?
  23. 23. REACTION FEATURES TIME OF MAXIMAL RISK TREATMENT Acute dystonia Spasm of muscles of tongue, face, neck, back; may mimic seizures; not hysteria 1 to 5 days Antiparkinsonian agents are diagnostic and curative Akathisia Motor restlessness; not anxiety or "agitation" 5 to 60 days Reduce dose or change drug; antiparkinsonian agents,a benzodiazepines or propranolol b may help Parkinsonism Bradykinesia, rigidity, variable tremor, mask facies, shuffling gait 5 to 30 days; can recur even after a single dose Antiparkinsonian agents helpfula Neuroleptic malignant syndrome Catatonia, stupor, fever, unstable blood pressure, myoglobinemia; can be fatal Weeks; can persist for days after stopping neuroleptic Stop neuroleptic immediately; dantrolene or bromocriptine c may help; antiparkinsonian agents not effective Perioral tremor ("rabbit syndrome") Perioral tremor (may be a late variant of parkinsonism) After months or years of treatment Antiparkinsonian agents often helpa Tardive dyskinesia Oral-facial dyskinesia; widespread choreoathetosis or dystonia After months or years of treatment (worse on Prevention crucial; treatment unsatisfactory
  24. 24.  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
  25. 25. 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.
  26. 26.  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
  27. 27.  19) Name the antipsychotic producing hypersalivation. Why does it cause that? how will you treat it?  Clozapine  Muscarnic agonism at M4 receptors.  Clonidine , anticholinergics, amitriptyline,scopolamine patch, ipratropium sublingual spray ,atropine 1% solution, botulinum toxin
  28. 28.  20) Name the longest acting antipsychotic. What are its other advantages?  Aripiprazole 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
  29. 29.  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.
  30. 30. 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.
  31. 31. 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.
  32. 32.  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
  33. 33.  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
  34. 34.  25) Name the only antipsychotic given sublingually.  Asenapine  26) Name a 1st generation antipsychotic with metabolic side effects. ( Wt gain, Hyperglycemia,Hypertriglyceremia)  Chlorpromazine
  35. 35. 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
  36. 36. THANK YOU!!!

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