Classification of CNS drugs
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1 Classification of CNS drugs Sedative-hypnotics Epilepsy and convulsion Parkinson disease Analgesics Central stimulants Antipsychotic drugs depression-mania Dementia Neurological (general and special) Psychological
2 Part 7 Sedative-Hypnotic Drugs Benzodiazepines Barbiturates Others
3 Sedatives ( 镇 静 药 ): 能 缓 和 激 动, 消 除 躁 动, 恢 复 安 静 情 绪 的 药 物 Hypnotics ( 催 眠 药 ): 能 促 进 和 维 持 近 似 生 理 睡 眠 的 药 物 中 枢 抑 制 药 多 数 随 剂 量 增 加 而 出 现 镇 静 催 眠 等 中 枢 抑 制 作 用, 故 合 称 为 镇 静 催 眠 药 (sedative-hypnotics)
4 Enhanced alertness Circadian rhythms of physiological functions: different functions in the waking and sleeping
5 Phases of the sleeping
6 A. Benzodiazepines Diazepam 地 西 泮 ( 安 定 ) CH3 N O Cl N
7 A. Benzodiazepines 1. Pharmacological effects and clinical uses (1) Antianxiety at small doses acting on limbic system (2) Sedative-hypnotic effects at relatively larger doses, no anesthetic effect; not remarkably affect on REM used for insomnia and preanesthetic medication
8 (3) Antiepileptic and anticonvulsant effects convulsion due various causes; status epilepticus (i.v.) (4) Centrally acting muscle relaxant effect relaxing the spasticity of skeletal muscle, probably by increasing presynaptic inhibition in the spinal cord. used for the treatment of skeletal muscle spasms caused by central or peripheral diseases. (5) Others A. Benzodiazepines amnesia ( 短 暂 性 记 忆 缺 失, i.v.) respiratory and CVS effects
9 A. Benzodiazepines 2. Mechanisms of actions (1) Sites of action: mainly acts on limbic system and midbrain reticular formation. (2) Interaction with GABA A receptor Benzodiazepines bind to specific, high affinity sites on the cell membrane, which are separate from but adjacent to the receptor for -aminobutyric acid (GABA). The binding of benzodiazepines enhances the affinity of GABA receptor for this neurotransmitter, resulting in a more frequent opening of adjacent chloride channels. - coagonist This in turn results in enhanced hyperpolarization( 超 极 化 )and further inhibition of neuronal firing.
10 Modulation mode of the central inhibitory transmitter GABA and the action sites of drugs
11 GABA BDZs Action of the central inhibitory transmitter GABA on Cl - influx and the action sites of benzodiazepines (BDZs)
12 The ascending arousal system, from the rostral pons through the thalamus and hypothalamus, modulates arousal and consciousness - Targets of sedative-hypnotics
13 ACh NE DA 5-HT
14 Centrally acting muscle relaxant effect: increasing presynaptic inhibition in the spinal cord
15 Centrally acting muscle relaxant effect: increasing presynaptic inhibition in the spinal cord
16 A. Benzodiazepines 3. Adverse effects (1) Central depression Most common: drowsiness and confusion (potentiated by ethanol or other central depressants) Ataxia; cognitive impairment Antagonized by BZ receptor antagonist flumazenil ( 氟 马 西 尼 ) (2) Tolerance and dependence Withdrawal syndrome: central excitation
17 A. Benzodiazepines (3) Others local pain, respiratory and CVS reactions (i.v.) teratogenic effects (4) Contraindications Myasthenia gravis Infants < 6 months Pregnancy and lactation mothers Elderly, heart/lung/liver/kidney dysfunction Fine motor coordination
18 A. Benzodiazepines Other benzodiazepines According to the metabolisms Long-acting: 艹 diazepam, chlordiazepoxide ( 氯 氮 卓 ), flurazepam ( 氟 西 泮 ) Intermediate-acting: Nitrozepam ( 硝 西 泮 ), flunitrozepam ( 氯 硝 西 泮 ), oxazepam ( 奥 沙 西 泮 ), estazolam ( 艾 司 唑 仑 ) Short-acting:triazolam ( 三 唑 仑 )
19 B. Barbiturates Phenobarbital 苯 巴 比 妥 O C NH NH CO CO C C2H5 C6H5
20 B. Barbiturates 1. ADME Inducing hepatic enzymes Alkalining urine: excretion 2. Pharmacological effects and clinical uses (1) Sedative-hypnotic effects (2) Preanesthetic medication (3) Antiepileptic and anticonvulsant effects
21 B. Barbiturates 3. Adverse effects (1) Central depression: including after effect (2) Tolerance and dependence: long-term uses (3) Acute poisoning supporting therapies alkalizing urine hemodialysis
22 C. Others Chloral hydrate 水 合 氯 醛 Sedative-hypnotic effects Anticonvulsant effect: usually used in children Hydroxyzine 羟 嗪 ( 安 泰 乐 ) Meprobamate 甲 丙 氨 酯 ( 眠 而 通 ) Buspirone 丁 螺 环 酮 Methaqualone 甲 喹 酮 ( 安 眠 酮 )
23 C. Others Antihistamines 抗 组 胺 药 Ethanol 乙 醇 Melatonin 褪 黑 素
24 Part 8 Central stimulants Psychomotor stimulants Respiratory center stimulants
25 A D. Psychomotor Central stimulants stimulants Psychomotor stimulants (mainly acting on cerebral cortex) Xanthines: caffeine 咖 啡 因 Related drugs Respiratory center stimulants Direct stimulation Indirect stimulation (reflex)
26 A Psychomotor stimulants Caffeine 咖 啡 因 O H 3 C N N CH 3 O N CH 3 N
27 A Psychomotor stimulants 1. Pharmacological effects (1) Central stimulation (2) CVS effects: cardiac stimulation, dilatation of vessels (3) Relaxing smooth muscles: airways, GI (4) Other effects: Gastric acid secretion, diuretic effect (5) Mechanisms of action:inhibiting PDE- camp ; antagonizing A 1 adenosine receptor & GABA receptor
28 A Psychomotor stimulants 2. Clinical uses Central depression Adjuvant of migraine and antipyretic-analgesic drugs 3. Adverse effects Central excitation Convulsion (overdose)
29 A Psychomotor stimulants Methylphenidate 哌 甲 酯 ( 利 他 灵 ) used for central depression caused by drugs or diseases; mild depression; child hyperactivity; enuresis; etc. Meclofenoxate 甲 氯 芬 酯 ( 氯 酯 醒 ) Adjuvant of central depressive diseases; enuresis; etc.
30 B Respiratory center stimulants Nikethamide 尼 可 刹 米 O C N C2H5 N C2H5
31 B Respiratory center stimulants 1. Pharmacological effects Direct (respiratory centre) and indirect (reflex via chemoreceptor) stimulation 2. Clinical uses Respiratory failure 3. Adverse effects Elevation of BP, tachycardia, tremor, convulsion
32 B Respiratory center stimulants Dimefline 二 甲 弗 林 ( 回 苏 灵 ) Direct stimulation Lobeline 洛 贝 林 ( 山 梗 菜 碱 ) Indirect stimulation
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