基礎(chǔ)醫(yī)學(xué)各論III課件：15_神經(jīng)系統(tǒng)藥理5_2013-10-28

1、神經(jīng)系統(tǒng)藥理5 一、抗精神病藥和抗抑郁藥 二、麻醉藥,一、抗精神病藥和抗抑郁藥,Antidepressant and antimanic drugs 抗抑郁和抗躁狂藥 Anxiolytics / antianxietics 抗焦慮藥 Antipsychotic drugs 抗精神分裂藥,Disorders of mood (affective disorders 情感障礙) are extremely common in medical practice. The severity of these conditions covers an extraordinarily broad rang

2、e, from normal grief(悲傷) reactions and dysthymia(心境惡劣) to severe, incapacitating illness that may result in death. Emotion（情緒）refers to transient responses to environmental, internal, and cognitive stimuli, while mood （心境）refers to the predominant emotional state over time.,Disorders of Mood,The sym

3、ptoms 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 s

4、tate characterized by arousal, vigilance, physiologic preparedness, and negative subjective states, may share certain critical circuits with fear.,Disorders of Mood,Monoamine hypothesis of Depression （單胺假說） 5-HT genetic basis of depression Used in treatments of depression (non-sensitive to TCAs) and

5、 Parkinson disease phenelzine (苯乙肼): non-selective selegiline (司來吉蘭): also used in Parkinson disease,MAOIs and Dietary Interactions,Tyramine(酪胺) is normally metabolized by MAO Tyramine is sympathomimetic (it acutely displaces NE from terminals to activate receptors) Ingesting tyramine during MAO inh

6、ibition results in hypertension, headache, palpitations, nausea, vomiting Tyramine is present in a number of foodstuffs, such as aged cheese, red wine, etc.,A. Antidepressant Drugs,NE reuptake inhibitors (NRIs) Selective norepinephrine reuptake inhibits rapid actions weaker sedative, anticholinergic

7、 and hypotensive effects desipramine (地昔帕明) maprotiline (馬普替林) nortriptyline (去甲替林) protriptylin (普羅替林) amoxapine (阿莫沙平),A. Antidepressant Drugs,Selective 5-HT reuptake inhibitors Selective serotonin reuptake inhibits (SSRIs) weaker sedative effects with anti-anxiety effects fluoxetine (氟西汀，百憂解)：抑郁癥

8、、神經(jīng)性貪食癥 paroxetine (帕羅西汀) sertraline (舍曲林),A. Antidepressant Drugs,5-HT/NE reuptake inhibitors Mixed serotonin/norepinephrine reuptake inhibits (SNRIs) rapid action less affinity with receptors higher safety venlafaxine (文拉法辛) milnacipram (米那普侖) lofepramine (洛夫帕明),A. Antidepressant Drugs,Noradrenerg

9、ic and specific serotonergic antidepressant (NaSSA) mirtezapine (米氮平) blocking presynaptic (auto- or hetero-) 2 receptor on both norepinephrine and serotonin (5-HT) pre-synaptic axons - increasing NE and 5-HT release; stimulating postsynaptic 1 receptors on serotonergic cell bodies - increasing the

10、firing rate of serotonergic neurons potently blocking postsynaptic 5-HT2A, 5-HT2C and 5-HT3 receptors attenuating 5-HT2C-mediated anxiety The net outcome of these effects is： increased noradrenergic activity increased serotonergic activity, esp. 5-HT1A receptors,B. Antimanic Drugs,Lithium carbonate

11、Carbamazepine Chlorpromazine Other related antiepileptic and antipsychotic drugs,B. Antimanic Drugs,1. Pharmacological effects and clinical uses Mood-stabilizing agent (1) Inhibiting NE and DA release (2) Interfering phosphatidylinositol (PI) metabolism (3) Substitute for sodium in generating action

12、 potentials and in Na+-K+ exchange across the membrane.,Lithium carbonate 碳酸鋰,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,B. Antimanic Drugs,(1)

13、Side effects Nausea, vomiting, abdominal pain, diarrhea, sedation, finger tremor, polyuria, etc. (2) Acute intoxication Mental confusion, coma, hyperreflexia(反射亢進(jìn)), gross tremor, dysarthria(構(gòu)音困難), seizures, etc. (3) Others Benign thyroid enlargement, renal damage,B. Antimanic Drugs,C. Anxiolytic dru

14、gs,1. Benzodiazepines see details in Sedative-Hypnotic Drugs 2. Buspirone（丁螺環(huán)酮） 5-HT1A receptor selective partial agonist, lowering 5-HT release Fewer sedative, hypnotic, memory-deficient effects No cross tolerance to benzodiazepines, and less potential of dependence,Schizophrenia(精神分裂癥),Neurologica

15、l Disorder - impairs ability to perceive, understand Tidal Volume Ventilation; PaCO2; Hypoxia Risk,Liver toxicity,“Halothane Hepatitis” Incidence post Halothane 0.003% Symptoms fever, anorexia(胃口不好), nausea altered liver function Rare liver failure & death,Malignant hyperthermia,Hypermetabolic syndr

16、ome hyperthermia, CO2, tachycardia, cyanosis, muscle rigidity Triggered by halogenated anesthetics & depolarizing muscle relaxants Familial relationship, i.e. genetic heterogeneity mutation in Ca2+ reuptake Incidence, 1/14,000 anesthesia (0.01%) Specific Treatment Dantrolene (inhibit Ca2+ release fr

17、om the sarcoplasmic reticulum),Nitrous oxide toxicity,Bone Marrow Depression megaloblastic, inhibition of B12 dependant enzymes Peripheral neuropathy Expansion of closed air spaces bowel obstruction, pneumothorax, bullous emphysema, middle ear obstruction, pneumocephalus CNS injury adults & neonates,NITROUS OXIDE KILLS NEURONS IN THE YOUNG AND THE OLD,Developing rat brain Exposure to a combination including nitrous, isoflurane & midazolam Persistent learning deficits,Early apoptosis,Late apoptosis,control,exposed,Intravenous Anesthetics(靜脈麻醉藥),Usually activate