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Drugs used in the Treatment of Psychological Disorders

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  1. Drugs used in the Treatment of Psychological Disorders • Antipsychotic drugs • Antidepressant and antimanic drugs • Anxiolytics

  2. A. Antipsychotic drugs Typical antipsychotic drugs are dopamine D2 receptor antagonists • Phenothiazines(吩噻嗪类) • Chlorpromazine 氯丙嗪 • Other phenothiazines • perphenazine 奋乃静;fluphenazine 氟奋乃静 • trifluoperazine 三氟拉嗪;thioridazine 硫利达嗪 • Thioxanthenes (硫杂蒽类) • Chlorprothixene氯普噻吨(泰尔登) • Butyrophenones(丁酰苯类) • Haloperidol 氟哌啶醇 • Droperidol 氟哌利多(氟哌啶)

  3. Others • Penfluridol五氟利多Longer duration of action, taking once weekly • Sulpride舒必利selectively acts on mesolimbic D2 receptors • few extrapyramidal reactions • Clozapine氯氮平Blocking D4 and 5-HT receptors • Risperidone利培酮Blocking D2and 5-HT2 receptors Actions of some secondary generation drugs

  4. A. Antipsychotic drugs • Phenothiazines(吩噻嗪类) Chlorpromazine 氯丙嗪

  5. A. Antipsychotic drugs • 1. Pharmacological effects • (1) Central effects • Blocking central D2 dopamine receptors

  6. A. Antipsychotic drugs • Dopaminergic pathways in the CNS • A. mesolimbic and mesocortical pathways • related to psychological activities and the therapeutic effects of drugs • B. nigrostriatal pathway • related to extrapyramidal function and the adverse effects of drugs • C. tuberoinfundibular pathway • related to hypothalamus endocrine effects of the drugs

  7. mesocortical and mesolimbic system Dopaminergic pathway related to psychological activities

  8. 中脑-皮层通路 黑质-纹状体通路 结节-漏斗通路 Most of antipsychotic drugs are DA receptor antagonists acting on DA pathways in the brain

  9. A. Antipsychotic drugs • a) Antipsychotic effects (neuroleptic effects) • for treatment of schizophrenia • controlling excitation and then hallucinations (weeks to months) • b) Antiemetic effects • inhibiting chemoreceptor trigger zone (CTZ) dopaminergic function

  10. A. Antipsychotic drugs • c) Poikilothermic effects • hypothermic anesthesia • artificial hibernation • d) Extrapyramidal effects • primary adverse effects • e) Potentiating the effects of central depressants • sedative-hypnotics, analgesics, general anesthetics, ethanol

  11. A. Antipsychotic drugs • (2) Autonomic nervous system effects • a) Hypotensive effects •  receptor blockade, postural hypotension • b) Anticholinergic effects • dry mouth, constipation, blurred vision, urinary retention, ect.

  12. A. Antipsychotic drugs • (3) Endocrine effects • prolactin  • ACTH, growth hormone 

  13. A. Antipsychotic drugs • 2. Clinical uses • (1) Treatment of schizophrenia • (2) Treatments of emesis and hiccough • used foremesisandhiccough(呃逆) • but ineffective on motion sickness • (3) Hypothermic anesthesia and artificial hibernation • combined with lowering room temperature

  14. A. Antipsychotic drugs • 3. Adverse effects • (1) Side effects • central depression • peripheral effects:postural hypotension, dry mouth, and other effects resulting from muscarinic and  receptor blockade

  15. A. Antipsychotic drugs • (2) Extrapyramidal effects • Duo to DA receptor block: • a) Parkinsonism • b) Akathisia • c) Acute dystonia • attenuated by central muscarinic antagonists • Duo to supersensitive to DA: • Tardive dyskinesia(迟发性运动障碍)

  16. 中脑-皮层通路 黑质-纹状体通路 结节-漏斗通路 Most of antipsychotic drugs are DA receptor antagonists acting on DA pathways in the brain

  17. A. Antipsychotic drugs • (3) Other central reactions • neuroleptic maglinant syndrome (神经阻滞药恶性综合征) • psychotic reactions • epilepsy and convulsion: lowering seizure threshold • (4) Allergic and hemological reactions • skin reactions, leukopenia, obstructive jaundice, liver damage

  18. A. Antipsychotic drugs • (5) CVS reactions • arrhythmia • hypotension: treated by receptor agonists • sudden death (elderly with CVS diseases) • (6) Endocrine reactions • hyperplasia of mammary glands (乳腺增生), galactorrhea (溢乳), amenorrhea (闭经), • child growth retard

  19. A. Antipsychotic drugs • (6) Acute intoxication • severe CNS depression, coma, severe hypotension • (7) Contraindications • epilepsy • coma • elderly with CVS disorders • severe hepatic and renal dysfunction

  20. A. Antipsychotic drugs • Other phenothiazines • perphenazine 奋乃静 • fluphenazine 氟奋乃静 • trifluoperazine 三氟拉嗪 • thioridazine 硫利达嗪 • more potent therapeutic effects and extrapyramidal effects

  21. A. Antipsychotic drugs • Thioxanthenes (硫杂蒽类) • Chlorprothixene氯普噻吨(泰尔登) • Used for the patients with symptoms of depression and anxiety

  22. A. Antipsychotic drugs • Butyrophenones(丁酰苯类) • Haloperidol 氟哌啶醇 • Droperidol 氟哌利多(氟哌啶) • Combined with fentanyl:neuroleptanalgesia(神经安定 [镇痛] 麻醉术)

  23. A. Antipsychotic drugs • Others • Penfluridol 五氟利多 • Longer duration of action, taking once weekly • Sulpride 舒必利 • selectively acts on mesolimbic D2 receptors • few extrapyramidal reactions • Clozapine 氯氮平 • Blocking D4 and 5-HT receptors • Risperidone利培酮 • Blocking D2and 5-HT2 receptors

  24. Disorders of Mood Disorders of mood (affective disorders情感障碍) are extremely common in medical practice. The severity of these conditions covers an extraordinarily broad range, from normal grief reactions and dysthymia to severe, incapacitating illness that may result in death. Emotion(情绪)refers to transient responses to environmental, internal, and cognitive stimuli, while mood(心境)refers to the predominant emotional state over time.

  25. Disorders of Mood The symptoms of depression are intense feelings of sadness, hopelessness, despair, and inability to experience pleasure in usual activity. Mania is characterized by the opposite behavior, that is, enthusiasm, rapid thought and speech patterns, and extreme self-confidence and impaired judgment. Anxiety, a state characterized by arousal, vigilance, physiologic preparedness, and negative subjective states, may share certain critical circuits with fear.

  26. Limbic lobe – Region for modulating emotion

  27. Orbital and medial perfrontal cortex Dorsolateral perfrontal cortex Hippocampus and amygdala Anterior cingulate gyrus Limbic regions involved in emotion and mood

  28. B. Antimanic Drugs • Lithium carbonate • Carbamazepine • Chlorpromazine • Other related antiepileptic and antipsychotic drugs

  29. B. Antimanic Drugs Lithium carbonate 碳酸锂 • 1. Pharmacological effects and clinical uses • Mood-stabilizing agent • (1) Inhibiting NE and DA release • (2) Interfering phosphatidylinositol (PI) metabolism

  30. B. Antimanic Drugs • 2. Adverse effects • Related to the serum concentration of Li+ • 0.8 – 1.5 mmol/L:therapeutic level • 1.6 – 2.0 mmol/L:GI reactions • > 2.0 mmol/L:CNS toxicity • Monitoring serum concentration of Li+ if possible

  31. B. Antimanic Drugs • (1) Side effects • Nausea, vomiting, abdominal pain, diarrhea, sedation, finger tremor, polyuria, etc. • (2) Acute intoxication • Mental confusion, coma, hyperreflexia, gross tremor, dysarthria, seizures, etc. • (3) Others • Benign thyroid enlargement, renal damage

  32. C. Antidepressant Drugs Enhancement of monoamine (5-HT, NE) transmitter function Inhibition of monoamine reuptake Inhibition of monoamine degradation

  33. Monoamine hypothesis(单胺假说) 5-HT  — genetic basis of depression & mania NE  — depression NE  — mania Modulation of monoamines in the synaptic space and/or the related post-synaptic receptors is of therapeutic importance

  34. Modulation of monoamines (NE and 5-HT) in the synaptic space and/or the related post-synaptic receptors is of therapeutic importance

  35. Long-term adaptations to antidepressant treatment

  36. Model of the neurotrophic hypothesis of antidepressant treatments and stress-related disorders

  37. Serotonin (5-HT) system related to depression

  38. Norepinephrine system related to depression

  39. C. Antidepressant Drugs Imipramine 丙咪嗪(米帕明) Tricyclic structure

  40. C. Antidepressant Drugs • 1. Pharmacological effects • (1) Central effects • Inhibiting reuptake of monoamine transmitters • Improving patient’s mood after 2 weeks • Sedative effects in normal subjects • (2) Autonomic effects • Muscarinic blocking effects • (3) Cardiovascular effects • Hypotension, tachycardia, arrhythmia

  41. C. Antidepressant Drugs • 2. Clinical uses • (1) Depression • Endogenous, melancholic, etc. • (2) Enuresis(遗尿) • (3) Anxiety and panic disorder

  42. C. Antidepressant Drugs • 3. Adverse effects • (1) Antimuscarinic effects • dry mouth, constipation, intraocular pressure increase, blurred vision, urinary retention, ect. • Contraindicated in prostatauxe and glaucoma • (2) CNS reactions • Confusion or delirium, depression-mania (bipolar patients) • (3) CVS reactions • Postural hypotension, sinus tachycardia, potential of arrhythmia

  43. C. Antidepressant Drugs • 4. Drug interactions • (1) Plasma protein binding • displacement by phenytoin, aspirin, scopolamine, phenothiazines, ect. • (2) MAO inhibitors • potentiating the effects of TCA, • contraindicated for combination with MAOIs • (3) Potentiating the effects of CNS depressant drugs

  44. C. Antidepressant Drugs Interaction of TCA with other types of drugs