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  • Slide 1
  • Antipsychotic Drugs Department of pharmacology
  • Slide 2
  • Classification Antipsychotic Drugs Antimanic drugs Antidepressants anxiolytics
  • Slide 3
  • Antipsychotic Drugs
  • Slide 4
  • Contents Overview Introduction of Schizophrenia Classification of antipsychotic drugs Chlorpromazine
  • Slide 5
  • Overview Antischizophrenic,neuroleptic drugs These agents are prescribed for treating schizophrenia or management of psychotic symptoms
  • Slide 6
  • Overview What is schizophrenia ? There appears to be a genetic component to schizophrenia. There is also evidence for changes in brain structure.
  • Slide 7
  • Schizophrenia schizophrenia Clinical Manifestations Characteristics-- perturbations affecting: language perception thinking volition Behavior social activity size of ventricles
  • Slide 8
  • MRIs of monozygotic twins show marked enlargement of the lateral ventricle in the twin with schizophreniz Unaffected twin Schizophrenic twin
  • Slide 9
  • Schizophrenia Syndrome overview: Typically begins in late adolescence Insidious onset. Poor outcome. Social withdrawal /perceptual distortions lead to chronic delusions /hallucinations.
  • Slide 10
  • Schizophrenia Positive Symptoms: Conceptual disorganization Delusions Hallucinations
  • Slide 11
  • Schizophrenia Negative Symptoms: Anhedonia Decreased emotional expression Impaired concentration Diminished socialization
  • Slide 12
  • The Nature of Schizophrenia Incidence is about 70% of hospital patients mental health hospital, with a strong, but not invariable, hereditary component.
  • Slide 13
  • Dopamine overactivity hypothesis (especially in left hemisphere). There is some evidence for involvement of 5-HT, and possibly other mediators, such as glutamate. The Nature of Schizophrenia
  • Slide 14
  • pathogenesis of schizophrenia Relevance of pathogenesis of schizophrenia to dopaminergic nerve in CNS:
  • Slide 15
  • Pathogenesis of schizophrenia 1.DA increases in the brain of the patient. 2.DR increases in the brain of the patient. 3.Functions of dopaminergic neurons increase.
  • Slide 16
  • pathogenesis of schizophrenia 4.Promotion of DA release induces episode of schizophrenia. 5.Blocking DR inhibit episode of schizophrenia.
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  • Slide 18
  • 1.limbic system- mesencephalic pathway emotion 2.cortico- mesencephalic pathway thinking and motion Four pathway of dopaminergic neurotransmission
  • Slide 19
  • 3.nigrostriatum pathway motion 4.hypothalamo-hypophysis pathway endocrine Four pathway of dopaminergic neurotransmission
  • Slide 20
  • Mechanism of action Antagonism of dopaminergic receptors (D 2 ) in CNS. 1.to block dopamine receptors in limbic system-mesencephalic pathway to improve emotion
  • Slide 21
  • Mechanism of action 2.to block dopamine receptor in cortico- mesencephalic pathway to restore thinking and motion therapeutic effects of drugs 1 and 2 are therapeutic effects of drugs
  • Slide 22
  • Mechanism of action the adverse effects of drugs 3.to block dopamine receptor in nigrostriatum pathway to cause extrapyramidal symptoms ----- the adverse effects of drugs
  • Slide 23
  • Mechanism of action the adverse effects of drugs 4.to bock dopamine receptor in hypothalamo-hypophysis pathway to cause endocrine dysfunction ----- the adverse effects of drugs
  • Slide 24
  • Classification of antipsychotic drugs Phenenothiazines (Chlorpromazine) Thioxanthenes (Tardan) Butyrophenones (Haloperidol) Atypicals (Clozapine)
  • Slide 25
  • Available Medications Typical medications Low potency agents - Chlorpromazine (sedation) High potency agents - Haloperidol (motor problems extrapyramidal effects) Atypical agents Clozapine - great Olanzapine - good Risperidone good Aripiprazole partial agonist
  • Slide 26
  • Typical Antipsychotics Good ability to treat hallucinations and delusions in most people within approximately 2 months
  • Slide 27
  • Typical Antipsychotics Limited effect on negative symptoms Flat affect Avolition Anhedonia Attentional impairment (Cognition)
  • Slide 28
  • Chlorpromazine
  • Slide 29
  • P harmacologic effects 1.effects on CNS (1) antipsychotic effect (2) sedation and synergism with other CNS depressives (3) antiemetic effects (4) effects on temperature-regulating mechanisms 2.altering endocrine 3.peripheral effects
  • Slide 30
  • 1.effects on CNS 1)antipsychotic effects (1)tranquilization: to make animals docile and friendly, rapidly to control manic states of psychotic patients and make them quiet (calming effect) and peaceful; to make patients feel indifferent, then induce sleep in few days.
  • Slide 31
  • 1.effects on CNS antipsychotic effects ( 2) intellect restoration, emotional quieting, reducing psychomotor excitement of the patient in few weeks. (3) to eliminate hallucination and illusion of the patient in few months.
  • Slide 32
  • (4) For normal person to induce sedation
  • Slide 33
  • Action mechanism Blocking dopamine D 2 receptor in limbic system- mesencephalic and cortico- mesencephalic pathways.
  • Slide 34
  • Dopamin receptor: two type, five subtype - DA1 (D1-like receptor): D1,D5 - DA2 (D2-like receptor): D2,D3, D4
  • Slide 35
  • D2 receptor activation motor activity aggravates schizophrenia D2 receptor blockade alleviation of schizophrenia
  • Slide 36
  • 2) sedation and synergism with other CNS depressives analgesics, sedative-hypnotics, anesthetics.
  • Slide 37
  • Pharmalogical effects 3)Antiemetic effect. - This is a results of blocking DA2 receptor. -In low doses, blocking DA2 receptor in chemoreceptor trigger zone(CTZ). -In high doses, chlorpromazine may directly depress the medulla vomiting center.
  • Slide 38
  • Pharmalogical effects 4)effect on temperature-regulating mechanism to inhibit temperature-regulating center in hypothalamus to induce poikilothermia (hypothermia, hyperthermia).
  • Slide 39
  • 4)effect on temperature-regulating mechanism in a cold climate it decrease temperature in body in a hot climate they can cause hyperthermia
  • Slide 40
  • (2) Autonomic nervous system effects a) Hypotensive effects receptor blockade, postural hypotension b) Anticholinergic effects---- Blocking M- receptor d ry mouth, constipation, blurred vision, urinary retention, etc. Pharmalogical effects
  • Slide 41
  • Endocrine system effect Increasing the lactogenic hormone. Increased levels of prolactin may lead to galactorrhea. Phenothiazines decrease FSH and ACTH. Decreasing release and secretion of pituitary growth hormone.
  • Slide 42
  • Prolactin FSH ACTH growth hormone.
  • Slide 43
  • Therapeutic uses 1. Psychotic disorders, all kind of schizophrenia.
  • Slide 44
  • Therapeutic uses 2. Nausea and vomiting.(except carsickness). ineffective for vomiting induced by stimulating vestibules of ears (motion sickness). effective for nausea and vomiting,
  • Slide 45
  • 3.Artificial hibernation* Artificial hibernation therapy can be used in serious patients with toxic infection, toxication and trauma etc. CPZ + pethidine + promethazine Artificial hibernation therapy Therapeutic uses
  • Slide 46
  • physical reduction of body temperature body temperature+ central depression(sleep) irritability to pathologic reaction; basal metabolism O 2 consumption; vasodilationto improve microcirculation to protect the important organs from damage to gain enough time for effective etiological treatment by other drugs.
  • Slide 47
  • T herapeutic uses 4.antipruritics: promethazine (H 1 blocking). 5. intractable hiccup: chlorpromazine.
  • Slide 48
  • Adverse effects 1.general adverse effects central depression, M-receptor blockage
  • Slide 49
  • 2.Extrapyramidal effects:Duo to DA receptor block: a) Parkinsonism a) Parkinsonism b) Akathisia b) Akathisia c) Acute dystonia c) Acute dystonia treated by central muscarinic antagonists treated by central muscarinic antagonists Duo to supersensitive to DA: Duo to supersensitive to DA: Tardive dyskinesia Tardive dyskinesia Adverse effects
  • Slide 50
  • acute dystonic reaction (facial grimacing and torticollis) tardive dyskinesia (sucking the lips and other involuntary facial movements). Adverse effects 2.extrapyramidal effects
  • Slide 51
  • patient display sucking of the lips and other involuntary facial movement. (The dyskinesia may persist for after discontinuation of the therapy).
  • Slide 52
  • 33.cardiovascular effects: orthostatic hypotension (First choice NA or AD?), syncope and reflex tachycardia. Adverse effects
  • Slide 53
  • 4.Inducing psychosis by drug 5.acute toxication po.

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