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chlorpromazine(Antipsychotic Drug)
 

chlorpromazine(Antipsychotic Drug)

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

    • Chlorpromazine.(Antipsychotic drug)
      SyedSunny-Uz-Zaman.
      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.
      Cont….
    • 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.
      Cont….
    • 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.
      Cont…
    • 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.
      Dip
      Rabby.
      Tushar.
      Ramim
      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