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chlorpromazine(Antipsychotic Drug)


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chlorpromazine(Antipsychotic Drug)

  1. 1. Chlorpromazine.(Antipsychotic drug)<br />SyedSunny-Uz-Zaman.<br />Rangpur Community Medical College,Rangpur,Bangladesh.4thyear Medical Student.<br />
  2. 2. Chlorpromazine.<br />Anti-psychotic Drug.(Phenothiazine Derivatives)<br />
  3. 3. Drug terminology.<br />Typical(First generation) antipsychotic.<br />Major tranquilizer- a misnomer.<br />Neuroleptics-prominent neurological side effects (EPS).<br />Fig: Chlorpromazine<br />
  4. 4. Psychosis & Schizophrenia.<br />John Nash.(1928) SydBarret (1946-2006) <br />Nobel Prize Winner in 1994 Rock star.<br />in mathematics.<br />
  5. 5. Psychosis & Schizophrenia.<br />Psychosis : “Cluster of disorders characterized by hallucination and / or loss of contact with reality.”<br />Psychosis disorders : i) Schizophrenia.ii) Schizoaffective disorder.iii) Delusional disorder.<br />Schizophrenia : “Neurological disease that affects a person’s perception,thinking,language,emotionand social behavior.”<br />
  6. 6. Psychosis & Schizophrenia.<br />Symptoms may be classified as :<br />Positive – “attention getter” symptoms i.e. hallucinations, delusions, bizarre behavior, disorganized speech<br />Negative– “crippling” symptoms i.e. apathy, lack of motivation, anhedonia<br />Cognitive - i.e. difficulty with attention, memory, and problem solving<br />Disorganized– i.e. disorganized speech, inappropriate affect<br />
  7. 7. Structure Activity Relationship.<br />Chemical structure of chlorpromazine.(C17H19ClN2S)<br />
  8. 8. Structure Activity Relationship.<br /> The phenothiazinestructure from the basic nucleus of chlorpromazine. <br /> Substitution at position (2) imparts antipsychotic activity <br />Substitution on the nitrogen at position(10) alters potency and adverse effects; the principal substitutions are: aliphatic, piperidine and piperazine.<br />
  9. 9. Pharmacokinetics.<br />Absorption: Readily absorbed from the GI tract.Bioavailability varies <br />due to first-pass metabolism by liver. <br />Volume distribution: 20 L/Kg<br />Protein binding : >90% to plasma proteins,primarilyalbumin.<br />
  10. 10. Pharmacokinetics.<br />Metabolism : Extensively metabolized in the liver and kidney. It is extensively metabolized by cytochrome P450 isozymes CYP2D6(mainly).Hydroxylation at position 3 and 7 of the phenothaizine nucleus. In urine,20% of chlorpromazine and its metabolized are excreted unconjugated in the urine as unchanged drug. The remaining 80% consists of conjugated metabolites.Themejor metabolites are the monoglucuronide of N-dedimethylchlorpromazine and 7-hyroxychlorpromazine.Approximately,37% of the administered dose of chlorpromazine is excreted in urine.<br />
  11. 11. Pharmacokinetics.<br />Route of elimination : Kidney, 37% in urine.<br />Half life :Approximately 30hours.<br />Route of administration: 1.Oral.2.parental.3.Rectal.<br />
  12. 12. Pharmacokinetics.<br />
  13. 13. Dopaminergic Pathways.<br />Mesocortical-mesolimbic pathway.<br />Nigrostriatal pathway.<br />Tuberoinfundibular pathway.<br />Medullaryperiventicular pathway.<br />Incerto hypothalamic pathway.<br />
  14. 14.
  15. 15.
  16. 16. Dopamine blockade effects.<br />Limbic and frontal cortical regions: antipsychotic effect.<br />Basal ganglia: Extrapyramidal side effects (EPS).<br />Hypothalamic-pituitary axis: hyperprolactinemia.<br />
  17. 17. Mechanism of Action.<br />Dopamine receptor blockade in mesolimbic-mesocorticaldopaminergic system. The primary therapeutic action of phenothiazines and haloperidol appears to involve blockade of the D2-receptor, which inhibits adenylylcyclase.<br />Cont….<br />
  18. 18. Fig: Mechanism of action of chlorpromazine.<br /><ul><li> Receptor affinity: i) Dopamin receptor.(D1,D2 )ii) Adrenergic receptor.(α1 )iii) Muscarinic receptor. (M2</li></li></ul><li>Pharmacological Effects.<br />On CNS:1.Mesolimbic pathway:i) Emotional quietening. ii) Affective indifference. iii) Psychomotor slowing.2.Nigro-striated pathway: Parkinsonism.3.Tubero-infundibular pathway:i) Gynaecomastia ii) Galactorrhoea. iii) Amenorrhoea. iv) Temderness of breast. <br />Cont….<br />
  19. 19. Pharmacological Effects.<br />4. Others:i) Increased appetite. ii) Hypothermia. iii) Sedation.<br /> On periphery : These effects are not produced by D2 receptor blocking.<br />1. Antimuscarinic effects:i) Dry mouth. ii) Dry eye. iii) Dry skin.<br />2.Antiadrenergic effects :i) postural hypertension. ii) Difficulty in ejaculation.<br /> Cont…<br />
  20. 20. Pharmacological Effects.<br /> 3. Hypersensitivity reaction :i) Agranulocytosis. ii) Skin rash. iii) Aplasticanaemia.<br />
  21. 21. Indications.<br />
  22. 22. Indications.<br /> Psychoses : 1.Management of schizophrenia. 2. As antiemetic. 3. Psychotic depression.(Along with anti-depressant) 4. As sedative. 5.Disturbed behavior in patients.<br /> Others : 1.Anxiety. 2. To potentiate hyponotics,analgesics& anaesthetics.<br />
  23. 23. Contraindication.<br /> Hypersensitive to this drug.<br />CNS depression.<br />Bone marrow depression.<br /> Parkinson disease.<br /> Sever hypotension.<br /> Hepatic impairment.<br /> Elderly patients.<br /> Dementia patients.<br /> In leukopenia.<br />
  24. 24. Adverse Effects.<br />
  25. 25.
  26. 26. Limitations in treatment with chlorpromazine.<br />No decrease in negative symptoms .<br /> Patients often unable to function in society .<br />Require medication – disease is not cured .<br /> Drop in number of institutionalized patients .<br />No substitute support system provided .<br />
  27. 27. Acknowledgement.<br /> Dr. AnupRahman Sir.<br />Prof.Dr. EhsanulBarri Sir.<br /> Dr. Joan Heller Brown, PhD<br />Special Thanks.<br />Dip<br />Rabby.<br />Tushar.<br />Ramim<br />And all of my friends for giving me the courage to make that path to step ahead.<br /> Ref: - -<br />