chlorpromazine(Antipsychotic Drug)
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chlorpromazine(Antipsychotic Drug)



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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: - -