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Psychotropic drugs. Liming Zhou ( 周黎明 ) Department of pharmacology. Classification. Antipsychotic Drugs Antimanic drugs Antidepressants anxiolytics. Antipsychotic Drugs. Contents. Overview Inreuduction of Schizophrenia Classification of antipsychotic drugs Chlorpromazine. Overview.
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Psychotropic drugs Liming Zhou (周黎明) Department of pharmacology
Classification • Antipsychotic Drugs • Antimanic drugs • Antidepressants • anxiolytics
Contents • Overview • Inreuduction of Schizophrenia • Classification of antipsychotic drugs • Chlorpromazine
Overview • Antischizophrenic,neuroleptic drugs • These agents are prescribed for treating schizophrenia or management of psychotic symptoms
Overview • What is schizophrenia ? • There appears to be a genetic component to schizophrenia. • There is also evidence for changes in brain structure.
Schizophrenia • schizophrenia • Clinical Manifestations • Characteristics-- perturbations affecting: • language • perception • thinking • volition • Behavior • social activity size of ventricles
Schizophrenia • Syndrome overview: • Typically begins in late adolescence • Insidious onset. • Poor outcome. • Social withdrawal /perceptual distortions lead to chronic delusions (错觉)/hallucinations (幻觉).
Schizophrenia • Positive Symptoms: • Conceptual disorganization • Delusions • Hallucinations
Schizophrenia Negative Symptoms: • Anhedonia (快感缺乏) • Decreased emotional expression • Impaired concentration • Diminished socialization
Classification of antipsychotic drugs • Phenenothiazines(吩噻嗪类) (Chlorpromazine) • Thioxanthenes(硫杂蒽类) (Tardan,flupenthixol) • Butyrophenones(丁酰苯类) (Haloperidol) • Atypicals )(非典型药物) (Clozapine)
Chlorpromazine (wintermine) • Pharmaciolgical effects • CNS effects 1.neuroleptic effect: hallucination and delusions(错觉)improvement
Mechanism of action Blockade dopaminergic neurotransmission -the limbic - nigrostriatal - hypothalamic system.
Dopamine Hypothesis: This idea was suggested by observation that drugs which reduced dopaminergic activity reduced acute symptoms/signs of psychoses. • Symptoms notably Decreased -- • agitation • anxiety • hallucinations
Four pathway of dopaminergic neurotransmission • 1)Mesolimbic-mesocortical pathway (one most closely related to behavior ) • 2)nigrostriatal pathway(it is involved in the coordination of voluntary movement) • 3)tuberoinfundibular pathway (inhibits prolactin secreation) • 4)medullary-periventricular pathway (the function is not clear ,may be involved eating behavior)
Dopamin receptor: two type, five subtype - DA1 (D1-like receptor): D1,D5 - DA2 (D2-like receptor): D2,D3, D4
D2 like receptors (D2, D3, D4) • Activate Gi cAMP • Block Ca++ channels • Open K+ channels • D2: putamen(壳核), olfactory tubercle(嗅结节) • D3: frontal cortex, medulla, midbrain • D4: ???
D2 receptor activation motor activity aggravates schizophrenia • D2 receptor blockade alleviation of schizophrenia
Neuroleptic effect: blocking DA2 • Side effect (extra-pyramidal symptoms.): blocking DA2
Pharmalogical effects • 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.
Pharmalogical effects • Altering temperature-regulating mechanisms. • in a cold climate it decrease temperature in body • in a hot climate they can cause hyperthermia
Pharmalogical effects • Sympathetic and parasympathetic nervous system effect: -Blocking α-adrenergic receptor Orthostatic hypotension. -Blocking M-receptor. Blurred vision Constipation Dry mouth Decreased sweating
Pharmalogical effects • Endocrine system effect • Increasing the lactogenic hormone(催乳素).Increased levels of prolactin may lead to galactorrhea (溢乳). • phenothiazines decrease FSH and ACTH. • Decreasing release and secretion of pituitary growth hormone.
Prolactin • FSH • ACTH • growth hormone.
Therapeutic uses • 1. Psychotic disorders, all kind of schizophrenia. • 2. Nausea and vomiting.(except carsickness). • 3. Decrease the temperature. • 4. Control of intractable hiccup(呃逆打嗝). • 5.Therapy gigantism(巨人症).
untoward effects • (1) Special side effect: Extrapyramidal symptoms • A. Parkinsonian syndrome: the patients display rigidity(僵化)and tremor • B. Acut dystonia: patients display facial grimacing (面部的歪扭,) torticollis(斜颈) • C.Akathisia (静坐不能) • D. tardive dyskinesia (迟发性运动障碍)
patient display sucking of the lips and other involuntary facial movement. (The dyskinesia may persist for after discontinuation of the therapy).
Untoward effects • (2)General side effect: • A. CNS depression • B. M-receptor blocking: The symptom of M- receptor blocking • C. Orthostatic hypotension
Untoward effects • (3)Inducing psychosis by drug • (4)seizure and epilepsy • (5)allergic reaction • (6)cardiovascular effect
Untoward effects • (7)Endocrine disorder: • Hyperprolactinemia--causes: For women: Amenorrhea(abnormal suppression or absence of menstrual flow), galactorrhea , infertility For men: impotence infertility,diminished libido • For children: decreasing growth.
Drug interaction: 1)Increasing CNS inhibition with ethanol, sedative-hypnotics, morphine. 2)Inhibiting the of L-Dopa (agonist of the doparmin-receptor). 3)Increase the dose with phentoin and carbamazepine.
Atypical antipsychotic drugs • Clozapine and Risperidone selectively inhibit D4 and 5-HT2-receptors. • Risperidone selectively inhibit D2 and 5-HT2-receptors. • Sulpiride selectively inhibit D2-receptors in the mesolimbic and mesocortical areas of the brain. • Sulpiride ,Clozapine and risperidone have low risk of extra-pyramidal adverse reaction.
Atypical antipsychotic drugs Sulpiride • Selectively inhibit D2-receptors in the mesolimbic and mesocortical areas of the brain. • Producing low extra-pyramidal adverse reaction.
Antimanic drug • Lithium carbonate
Pharmacodynamics Possible mechanisms of action: -effects on electrolyte/ion transport neurotransmitter -neurotransmitter release modulation influence on second messengers. Lithium salts how to affect second messengers?(learning by yourself)
Antidepressants • Overview • Classification • TCA Antidepressants
Overview • Depression is an alteration of mood characterized by sadness, worry, and anxiety. • The patient may suffer from losses of weight, libido, and enthusiasm.
Depression Clinical depression is a syndrome that may include: • Sustained mood disturbances • Impaired memory and concentration • Disturbed sleep • Reduced energy level • Reduced libido • Impaired sleep.
Depression • Patient complaints suggestive of depression may include: • Pain (headaches, body aches) • A mood of apathy, anxiety, or irritability • Sexual complaints • low energy, excessive tiredness • reduced capacity for enjoyment.
Classification of Antidepressant Drugs • Five of antidepressant • Tricyclic antidepressants (TCA) • Monoamine oxidase inhibitors (MAO) • NA reuptake inhibitors • Serotonin-specific reuptake inhibitors (SSRIs) • Serotonin and NA-specific reuptake inhibitors
Most antidepressants are believed to improve by increasing NT • Catecholamine • 5-HT stores
Tricyclic antidepressant TCAs Imipramine
Pharmalogic effects • CNS -In the depressed patients , an elevation of mood occur 2-3 weeks after administration begins, the latency period can be as long as 4 weeks. -The imipramine blocks the re-uptake of serotonin and NA
Pharmalogic effects Autonomic nervous system Blocking m-receptor
Pharmalogic effects Cardovascular effect: • Hypotensin (blocking α receptor) • Tachycardia
Mechanism of TCA: • Blocking re-uptake of neurotransmitter • Norepinephrine(NA) • Serotonin(5-HT)
Clinic use • 1)Therapy depression • 2)Therapy enuresis • 3)Therapy anxiety and phobic-anxiety syndromes • 4)Obsessive-compulsive neurosis companied by depression