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chlorpromazine(Antipsychotic Drug)

chlorpromazine(Antipsychotic Drug)



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I think its very helpful for early medical student for building their concept clear.

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    chlorpromazine(Antipsychotic Drug) chlorpromazine(Antipsychotic Drug) Presentation Transcript

    • Chlorpromazine.(Antipsychotic drug)
      Rangpur Community Medical College,Rangpur,Bangladesh.4thyear Medical Student.
    • Chlorpromazine.
      Anti-psychotic Drug.(Phenothiazine Derivatives)
    • Drug terminology.
      Typical(First generation) antipsychotic.
      Major tranquilizer- a misnomer.
      Neuroleptics-prominent neurological side effects (EPS).
      Fig: Chlorpromazine
    • Psychosis & Schizophrenia.
      John Nash.(1928) SydBarret (1946-2006)
      Nobel Prize Winner in 1994 Rock star.
      in mathematics.
    • Psychosis & Schizophrenia.
      Psychosis : “Cluster of disorders characterized by hallucination and / or loss of contact with reality.”
      Psychosis disorders : i) Schizophrenia.ii) Schizoaffective disorder.iii) Delusional disorder.
      Schizophrenia : “Neurological disease that affects a person’s perception,thinking,language,emotionand social behavior.”
    • Psychosis & Schizophrenia.
      Symptoms may be classified as :
      Positive – “attention getter” symptoms i.e. hallucinations, delusions, bizarre behavior, disorganized speech
      Negative– “crippling” symptoms i.e. apathy, lack of motivation, anhedonia
      Cognitive - i.e. difficulty with attention, memory, and problem solving
      Disorganized– i.e. disorganized speech, inappropriate affect
    • Structure Activity Relationship.
      Chemical structure of chlorpromazine.(C17H19ClN2S)
    • Structure Activity Relationship.
      The phenothiazinestructure from the basic nucleus of chlorpromazine.
      Substitution at position (2) imparts antipsychotic activity
      Substitution on the nitrogen at position(10) alters potency and adverse effects; the principal substitutions are: aliphatic, piperidine and piperazine.
    • Pharmacokinetics.
      Absorption: Readily absorbed from the GI tract.Bioavailability varies
      due to first-pass metabolism by liver.
      Volume distribution: 20 L/Kg
      Protein binding : >90% to plasma proteins,primarilyalbumin.
    • Pharmacokinetics.
      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.
    • Pharmacokinetics.
      Route of elimination : Kidney, 37% in urine.
      Half life :Approximately 30hours.
      Route of administration: 1.Oral.2.parental.3.Rectal.
    • Pharmacokinetics.
    • Dopaminergic Pathways.
      Mesocortical-mesolimbic pathway.
      Nigrostriatal pathway.
      Tuberoinfundibular pathway.
      Medullaryperiventicular pathway.
      Incerto hypothalamic pathway.
    • Dopamine blockade effects.
      Limbic and frontal cortical regions: antipsychotic effect.
      Basal ganglia: Extrapyramidal side effects (EPS).
      Hypothalamic-pituitary axis: hyperprolactinemia.
    • Mechanism of Action.
      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.
    • Fig: Mechanism of action of chlorpromazine.
      • Receptor affinity: i) Dopamin receptor.(D1,D2 )ii) Adrenergic receptor.(α1 )iii) Muscarinic receptor. (M2
    • Pharmacological Effects.
      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.
    • Pharmacological Effects.
      4. Others:i) Increased appetite. ii) Hypothermia. iii) Sedation.
      On periphery : These effects are not produced by D2 receptor blocking.
      1. Antimuscarinic effects:i) Dry mouth. ii) Dry eye. iii) Dry skin.
      2.Antiadrenergic effects :i) postural hypertension. ii) Difficulty in ejaculation.
    • Pharmacological Effects.
      3. Hypersensitivity reaction :i) Agranulocytosis. ii) Skin rash. iii) Aplasticanaemia.
    • Indications.
    • Indications.
      Psychoses : 1.Management of schizophrenia. 2. As antiemetic. 3. Psychotic depression.(Along with anti-depressant) 4. As sedative. 5.Disturbed behavior in patients.
      Others : 1.Anxiety. 2. To potentiate hyponotics,analgesics& anaesthetics.
    • Contraindication.
      Hypersensitive to this drug.
      CNS depression.
      Bone marrow depression.
      Parkinson disease.
      Sever hypotension.
      Hepatic impairment.
      Elderly patients.
      Dementia patients.
      In leukopenia.
    • Adverse Effects.
    • Limitations in treatment with chlorpromazine.
      No decrease in negative symptoms .
      Patients often unable to function in society .
      Require medication – disease is not cured .
      Drop in number of institutionalized patients .
      No substitute support system provided .
    • Acknowledgement.
      Dr. AnupRahman Sir.
      Prof.Dr. EhsanulBarri Sir.
      Dr. Joan Heller Brown, PhD
      Special Thanks.
      And all of my friends for giving me the courage to make that path to step ahead.
      Ref: -www.drugbank.ca - www.en.wikipedia.org - www.iucr.org