Part 8. Anti-psychiatric disorders

( 抗精神失常药 )

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Outline1.Concept of mental disorders: Mental disorder = Psychiatric disorder(1)Morbidity ( 发病率 )of mental disorder in our country: 16 million 1982: 12.67 ‰, 70’: 3.20 ‰, 1993: 13.47 ‰, 80’: 9.33 ‰, 2000: 15.56 ‰. 90’: 10.67 ‰, in Guangdong: 16.36 ‰, in Beijing: 34.34 ‰, in Shanghai: 38.46 ‰. 2006/3/27: in Zhejiang, 17.3 ‰.

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(2)Etiology of mental disorder ▲ Genetic factor( 遗传因素 ): monovular twins: 61%~70%, binovular twins: 10%~13%. ▲ Diathetic factor( 素质因素 ): ▲ Social psychogenic factor ( 社会心理因素 ): ▲ Age and sex( 年龄和性别 )

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(3)Classification of mental disorders (ICD-10, CCMD-2R)

Schizophrenia√ ( 精神分裂症 ) Psychosis Mania√ ( 精神病 ) ( 燥狂症 ) Depression√ Mental ( 抑郁症 )disorders Anxiety ( 焦虑症 ) Neurosis Hysteria ( 神经官能症 ) ( 癔症 ) Neurasthenia ( 神经衰弱 )

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Other mental disorders: 脑器质性精神障碍 , 感染性精神障碍 , 中毒性精神障碍 , 心因性精神障碍 , 老年期精神障碍 , 儿童少年精神障碍 , 酒与药物滥用相关精神障碍 , 人格障碍 , 精神发育迟缓 , 等 .

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2. Classification of drugs treated mental disorders:

(1)Anti-schizophrenic drugs( 抗精神分裂症药 )

=Anti-psychotic drugs( 抗精神病药 )

(2)Anti-manic drugs( 抗躁狂症 )

(3)Anti-depressant( 抗抑郁症药 )

(4)Anti-anxiety drugs( 抗焦虑症药 )

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Part 1. Anti-psychotic drugs: Ⅰ. Concept of Schizophrenia ( 精神分裂

症 )

Ⅱ. Distribution of D2 receptor in CNS Ⅲ. Specific drugs: Chlorpromazine( 氯丙嗪 ) Chlorprothixene( 氯普噻吨 ) Haloperidol( 氟哌啶醇 ) Penfluridol( 五氟利多 ) Sulpirine( 舒必利 ) Clozapine( 氯氮平 )

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Ⅰ. Concept of Schizophrenia: Schizophrenia ( 精神分裂症 ) is the most

common kind of psychosis, more than 50% of psychosis.

Schizophrenia frequently occurring in puberty ( 青春期 ), fall ill rarely after 40 years old.

The causes of illness are not clear, probably owing to genetic factors and environmental factors together.

Schizophrenia can be divided into 2 types: TypeⅠ and Type .Ⅱ

hallucination( 幻觉 ), delusion( 妄想 )8

Pathophysiology of Schizophrenia: Functional disorder of CNS

neurotransmitter and receptors, especially CNS transmitter Dopamine increased.

Experimental study showed that the symptoms of schizophrenia exacerbated when Dopamine in CNS increased, and the symptoms of schizophrenia abated when Dopamine in CNS decreased.

There are 4 subtypes of dopamine receptor in CNS, they are D1, D2, D3, D4 receptor.

The most effective anti-schizophrenia drugs are blocking agents of D2 receptor.

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Ⅱ. Distribution of D2 receptor in CNS

(1)Meso-cortical pathway( 中脑 - 皮质通路 ): 与精神理智及行为活动有关 ;

(2)Meso-limbic pathway( 中脑 - 边缘系统通路 ): 与情绪情感活动有关 ;

(3)Nigro-striatal pathway( 黑质 - 纹状体通路 ): 与锥体外系的运动功能有关 ;

(4)Tubero-infundibular pathway( 结节 -漏斗通路 ): 与垂体内分泌功能有关 .

There are 4 neural pathways of dopaminergic nerve in CNS:

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In addition, D2 receptors distributed at the postsynaptic membrane of:

①Chemoreceptor trigger zone(CTZ) of the medulla oblongata( 延脑的催吐化学感受区 ); ②Heat-regulating center of hypo-thalamus( 下丘脑体温调节中枢 )

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The effects of anti-schizophrenia drugs blocking D2 receptor of some regions are therapeutic effect;

The effects of anti-schizophrenia drugs blocking D2 receptor of other regions are adverse reaction, such as extrapyramidal symptoms( 锥体外系症状 ).

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Ⅲ. Specific drugs: Chlorpromazine( 氯丙嗪 , wintermin,

冬眠灵 ) 1. Pharmacological effects : Effects of Chlorpromazine include CNS

effects & Peripheral effects. CNS effects: block D2 receptor of CNS, those

effects are therapeutic effect or adverse reaction.

Peripheral effects: block receptor and M receptor of periphery, mainly cause adverse reaction.

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(1)CNS effects: ①Anti-psychotic effects: Chlorpromazine block D2 receptor of Meso-cortical pathway ( 中脑 - 皮质通路 ) and Meso-limbic pathway ( 中脑 - 边缘系统通路 ), to inhibit the mental activity of psychosis patients selectively.

There are markedly curative effects in acute psychosis of unknown etiology, including acute idiopathic psychosis ( 特发性精神病 ) and acute exacerbations of schizophrenia ( 精神分裂急性发作 ). It is also effective to mania ( 躁狂症 ).14

②Anti-emetic effects( 镇吐作用 ) to block D2 receptor of CTZ ( 催吐化学感受区 ) of the medulla oblongata ( 延髓 ), it can be used to treat emesis ( 呕吐 ). ③Affecting body heat regulation( 影响体温调节作用 ) to block D2 receptor of heat-regulating center ( 体温调节中枢 ). This action is different to anti-pyretics ( 解热药 ). 15

④Extra-pyramidal ( 锥体外系 ) effects Owing to blocking D2 receptor of Nigro-striatal pathway ( 黑质 - 纹状体通路 ).

if taking chlorpromazine for long time, the functions of cholinergic nerve of CNS will be predominant:

Extra-pyramidal symptoms: Parkinson’s syndrome( 帕金森综合征 ) Acute myodystonia( 急性肌张力不全 ) Akathisia( 静坐不能 ) Tardive dyskinesia( 迟发性运动障碍 )16

(2)Endocrine system

Chlorpromazine blocking D2 receptor of tubero-infundibular pathway ( 结节 -漏斗通路 ), to affect functions of hypothalamus ( 下丘脑 ) endocrine. `

—— Adverse reaction: menstrual ( 月经 ) disorder, feminization and lactation ( 女性化症状 ), exacerbation of breast cancer.

—— Clinical use: to treat gigantism ( 巨人症 ), owing to reduce the secretion of pituitary ( 垂体 ) growth hormone. 17

(3)Automatic nervous system ①-receptor blockade: Vasodilatation, Blood pressure . Owing to tolerance, not be used to treat hypertension. Orthostatic hypotension( 体位性低血压 )

②M-receptor blockade: ADRs: dry in the mouth( 口干 ), constipation( 便秘 ), blurred vision( 视力模糊 ), etc.

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2. Clinical uses: (1)to treat psychosis ★ Various type schizophrenia ( 精神分裂 ). including acute and chronic patients, especially acute type. ★Mania ( 躁狂 ). ★ Other psychosis with exciting, tension and delusion.

But Chlorpromazine is ineffective for depression ( 抑郁 ). The condition of some patients with depression will exacerbate after taking chlorpromazine. 19

(2)Emesis ( 呕吐 ) and intractable hiccough ( 顽固性呃逆 ) to treat various causative emesis, including emesis result of gastroenteritis, cancer, radiation disease, uremia ( 尿毒症 ) and drug induced emesis. But, it is in-effective to emesis of car sickness and sea sickness. beside anti-emetic effect, also used to intractable hiccough( 顽固性呃逆 ). Mechanism of anti-emetic effect: Small dose: blocking D2 receptor in CTZ of the medulla oblongata ( 延髓催吐化学感受区 ); Large dose: directly inhibiting emetic center ( 呕吐中枢 ).

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(3)Poikilothermic effects( 变温作用 ) ★ Hypothermic anesthesia( 低温麻醉 ) when anesthesia, injected Chlorpromazine with physical cooling(ice bath), Body temperature

Hypothermic anesthesia( 低温麻醉 ): ≤ 30 . 15~20 ℃ min, Deep hypothermic anesthesia( 深低温麻醉 ): ≤ 18 . 45~60 ℃ min,

★ Artificial hibernation( 人工冬眠 ) Chlorpromazine(Wintermin, 冬眠灵 ) +Dolantin( 度冷丁 )+Phenergan( 异丙嗪 )

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3. Adverse reaction (1)Extra-pyramidal effects ( 锥体外系 ) Can be treated with central anti-cholinergic agents —— Artane( 安坦 ), or

Scopolamine( 东莨菪碱 ), but can not be treated with L-dopa. (2)Allergy: Skin rash, dermatitis, leukopenia ( 白细胞减少 ), and obstructive jaundice ( 黄疸 ), etc. (3)Others: M and receptor blockade, and orthostatic hypotension ( 体位性低血压 ).

Contraindication: Epilepsy ( 癫痫 ), glaucoma, cardiovascular disorders, severe hepatic damage, etc.

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Chlorprothixene( 氯普噻吨 ,Tardan, 泰尔登 )

Its anti-schizophrenic ( 精神分裂 ) effects is weaker, but with marked anti-depression and anti-anxiety ( 抗焦虑 ) effects.

Clinical uses: used to schizophrenia with anxiety and anxiety-depression. 23

Haloperidol( 氟哌啶醇 ) Its anti-schizophrenic effects and extra-pyramidal effects are stronger, and with stronger effects of anti-mania( 抗躁狂 ), anti-hallucination( 抗幻觉 ), and anti-delusion( 抗妄想 ).

Clinical uses: 1. To treat schizophrenia with exciting, hallucination and delusion, 2. To treat mania as well.

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Penfluridol( 五氟利多 ) longer-acting anti-psychotic effects, by po. 1 time / 1 week.

to treat chronic patients for long-term.

  Sulpirine( 舒必利 ) ADR and extra-pyramidal effects are less,

to treat acute and chronic schizophrenia for long-term, and effective to depression.

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Clozapine( 氯氮平 ) 1. Effects and characteristics: It is a new type of anti-psychotic drug, its anti-psychotic effect is high potency. It can not block D2 receptor, but can block D4 receptor. Its CNS anti-cholinergic effect is stronger, therefore, there is not extra-pyramidal effect almost. 2. Adverse reaction: WBC (granulocytoponia)

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Part 2. Anti-manic andanti-depressant drugs

Mania( 躁狂症 ):

Depression( 抑郁症 ):

——Affective psychosis( 情感性精神病 )

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Pathophysiology of Mania and Depression:

5-HT (5 - 羟色胺 ) in the brain is the basis of Mania-depression,

when 5-HT , NA : Mania

when 5-HT , NA : Depression

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Ⅰ. Anti-manic drugs Antiepileptic drug——Carbamazepine ( 卡马西平 ),

Antipsychotic drug——Chlorpromazine ( 氯丙嗪 ) and Haloperidol ( 氟哌啶醇 ), there are marked anti-manic effects.

Let’s introduce another anti-manic drug now:

Lithium Carbonate( 碳酸锂 )

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Lithium Carbonate( 碳酸锂 ) 1. Pharmacological effects: therapeutic dose(1~2g/day, po) to normal subjects: no affection; to manic patients: marked curative effect. Mechanisms of anti-manic effects:　 　　 inhibiting the release of NA and DA, promoting NA and DA reuptake, to decrease the concentration of the neurotransmitters in the synaptic cleft ( 突触间隙 ).

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2. Clinical uses: (1)Mania( 躁狂症 ) (2)Manic-depressive psychosis( 躁狂抑

郁症 ) —— mood-stabilizing( 情绪稳定药 ).

(3)Manic symptoms of schizophrenia ( 有躁狂症状的精神分裂症 ).

3. Adverse reaction: GI reaction and CNS reaction

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Relationship of blood concentration(Cp) and drug reaction Cp drug reaction0.8~1.2 mEq/L Therapeutic concentration1.6~2.0 mEq/L GI reaction, include: nausea, emesis, diarrhea, etc. ＞ 2.0 mEq / L CNS toxicity, include: hypermyotonia( 肌张力增高 ), ataxia( 共济失调 ), disturbance of consciousness( 意识障碍 ), coma( 昏迷 ). blood concentration monitoring, to control dosage. 32

Ⅱ. Antidepressants A. Tri-cyclic agents(TCAs, 三环类药物 ):

Imipamine ( 米帕明 , 丙咪嗪 )

1. Pharmacological effects: (1)CNS effects(Anti-depressant effects): to normal subjects: sleepiness, light headache, slight fall in blood pressure, and certain anti-cholinergic effects.

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to depressed patients: It can elevate mood markedly, mental stimulation—— marked anti-depressive effect.

The effect is different to CNS stimulants(such as caffeine), therefore, the mental stimulant effect of imipamine ( 米帕明 ) is selective.

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(2)Cardiovascular effects: ①direct action: inhibiting heart, —— cardiac contractility , BP : ②indirect action: inhibiting NA reuptake of sympa-thetic nervous ending of heart, NA in synaptic cleft, activating 1 receptor of heart. —— ectopic cardiac rhythm and arrhythmia ( 心率失常 ).

(3)M-cholinergic blockade　　——　Adverse reaction

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Mechanisms of antidepressanteffects: Experiments show that TCAs ( 三环类药物 ) can block the reuptake of NA and 5-HT, to increase the concentration of NA and 5-HT in the synaptic cleft ( 突触间隙 ), to promote the transmission function of synapse, to exert anti-depressive effects.

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2. Clinical uses: (1)All depression The curative effects are well to endogenous( 内源性 ), reactive, and involutional( 更年期 ) depression . Depressive state of schizophrenia, the curative effect is bad. (2)Enuresis( 遗尿症 ) (3)Anxiety and Phobia( 恐惧症 )

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3. Adverse reaction: (1)M-cholinergic blockade: Thirsty, constipation ( 便秘 ), blurred vision. (2)Cardiovascular effects: Hypotension, tachycardia ( 心动过速 ), arrhythmia. (3)Allergy.

Other tricyclic drugs ( 三环类药物 ): Amitriptyline( 阿米替林 ), Clomipramine ( 氯米帕明 ), Doxepin( 多塞平 , 多虑平 ), etc.

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B. NA reuptake inhibitors ( 摄取抑制剂 ): The drugs of this kind can selectively inhibit NA reuptake, increase the concentration of NA in synaptic cleft of CNS.

The curative effects of the drugs take place faster and ADRs are less.

Such as Desipramine( 地昔帕明 ), Maprotiline( 马普替林 ), Nortriptyline ( 去甲替林 ), Protroptyline( 普罗替林 ), Amoapine( 阿莫沙平 ), etc.

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C. 5-HT reuptake inhibitor: The drugs of this kind can selectively inhibit 5-HT reuptake, increase the concentration of 5-HT in synaptic cleft of CNS. Those drugs are effective to the patients whose 5-HT decreased in brain. Such as Fluoxetine( 氟西汀 ), Paro-xetine( 帕罗西汀 ), Sertraline(舍曲林 ), etc.

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D. Other antidepressants There are many other anti-depressants mechanism, such as tryptophan ( 色氨酸 ), it is the pro-amino acid of 5-HT, can be used to treat some intractable(难治性的 ) depressant patients at abroad.

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Part 9. Analgesics( 镇痛药 )

 

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Outline

★ Classification of analgesics: 1. Opioid analgesics( 阿片类镇痛药 )

 2. Antipyretic, analgesic, and anti-inflammatory drugs( 解热镇痛抗炎药 )

(1)Opium alkaloids( 阿片生物碱类 )(2)Synthetic opioid analgesics( 人工

合成的阿片类镇痛药类 )

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 (A)Opium alkaloids: Morphine(吗啡 ), Codeine(可待因 )(B)Synthetic opioid analgesics: Pethidine( 哌替啶 ), etc.(C)Non-opioid analgesics: Rotundin(罗通定 )(D)Antagonist of opium receptors: Naloxone(纳洛酮 ), etc.

Contents

Part 9. Analgesics

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(A)Opium alkaloids: Opium alkaloids extracted from opium ( 阿片 );

Opium( 阿片 ) came from poppy(罂粟 ).

Analgesics

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Opium as therapeutic drugs, it is called “ 阿片” ;

as dope( 毒品 ), it is called “鸦片” , “大烟” 或 “烟土” .

There are more than 20 alkaloids in opium, the alkaloids account for 25% of opium.

Morphine(吗啡 ) is 10% of opium, Codeine(可待因 ) is 0.5% of opium.

Analgesics

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Morphine(吗啡 )

O

N CH3

HO

HO

Morphine(吗啡 )

Opioid alkaloids

Sertürner(German) extracted from opium in 1806. “Morphine” came from Greece “morpheus” ––––Greek god of dream (梦之神 ).

O

N CH3

OCOH3C

H3C OCO

Heroin(海洛因 )

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1. Pharmacological effects: (1)CNS effects: ①Analgesia ( 镇痛 ) and sedation ( 镇静 ):

(a)Analgesia: effective to various pain, including “sharp pain”(锐痛 ) and ‘‘Dull pain”(钝痛 );

(b)Sedation; (c)Improving mood: euphoria(欣快感 ).

Morphine

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Mechanisms of analgesic effects: Morphine and opioids can activate opium receptor of different regions in CNS to effect analgesia. There are 4 subtypes of opium receptor in CNS at least: receptor, 与脊髓以上水平的镇痛 , 以及缩瞳、呼 吸抑制、改善情绪、欣快感和精神依赖性有关 ; receptor, 与脊髓以上水平的镇痛 , 缩瞳 , 欣快感有关 , 还与胃肠道平滑肌兴奋 , 张力提高和活动减少有关 ; receptor, 与脊髓水平的镇痛有关 , 并使病人烦躁不安 ;

Morphine

receptor, 与镇痛无关 , 兴奋可引起幻觉 , 焦虑和 烦躁不安 .  50

Endogenous ligand of opium receptor:

There are more than 20 kinds of endogenous opioid peptides, such as:

Endorphin( 内啡肽 ), , receptor Enkephalin( 脑啡肽 ), receptor Dynorphin(强啡肽 ), receptor —— endogenous ligand.

Morphine with affinity and intrinsic activity to opium receptor.

MorphinMorphinee

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Peripheral mechanisms of pain

Brain

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sensory neuron receiving neuron

SP

SP SP CNS

E SP

E E

opium receptor

　　　　　　　　　　　　　　　　　　　　　　neuron contained enkephalin ( 脑啡

肽 )

Morphine

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②Respiratory depression The therapeutic doses of morphine

slightly inhibit respiratory center, to decrease sensitivity to CO2, to slow down respiratory frequency, the large doses markedly inhibit respiratory center.

▲ stimulating receptor, to depress respiratory center.

▲ at least in part by virtue of direct effect on the brainstem respiratory centers.

③Cough suppression to depress coughing center.

Morphine

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④Myosis (缩瞳 ): Morphine and other receptor agonists can cause constriction of the pupil by an excitatory action on the parasympathetic nerve (副交感神经 ) innervating (支配 ) the pupil.

when morphine intoxication: pin-point pupils(针尖样瞳孔 )

⑤Emesis ( 呕吐 ): stimulating CTZ.

Morphine

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(2)Peripheral effects: ①Gastrointestinal effects Morphine can stimulate receptor of

smooth muscle(circular muscle), and diminish gland secretions.

▲Anti-diarrhea and constipation: owing to decrease of gland secretion and

propulsive peristalsis(推进性蠕动 ) ; and owing to CNS depression. ▲Pressure in biliary tract (胆道 ) :  inducing biliary colic (胆绞痛 ).

Morphine

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②Cardiovascular effects: ▲ Peripheral small vessels dilatation ● promoting histamine release, dilating

peripheral small vessels, including arteriolar and venous dilatation.

● stimulating opium receptor of nucleus of solitary tract(孤束核 ) in CNS, tone of vasomotor centers ( 血管舒缩中心 ) , BP.

orthostatic hypotension( 体位性低血压 ) and syncope(晕厥 ).

Morphine

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▲ Cerebral vasodilatation ( 脑血管扩张 ) Respiratory depression, CO2, cerebral

blood dilatation intracranial pressure (颅内压 ) ,

therefore, contraindication for the patients of craniocerebral injury (颅脑外伤 ).

③Other effects ▲Ureteral (输尿管 ) and vesical sphincter

(膀胱括约肌 ) tension: urinary retention ( 尿潴留 ) ▲Bronchoconstriction: because of releasing histamine, to contract

smooth muscle of bronchus directly / large dose.

Morphine

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(3)Immunosuppression: ①inhibiting cellular immunity Morphine can depress the activity of NK cell, inhibit T cell proliferation by ConA, inhibit phagocytic function etc.

②depressing humoral immunity Morphine can affect the synthesis and release of cytokines( 细胞因子 ), such as:

IL(interleukin, 白细胞介素 ): IL-1, IL-2, IL-10;

TNF(tumor necrosis factor, 肿瘤坏死因子 ): TNF-, TNF-, etc.

Morphine

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2. Clinical uses: (1)Analgesia ( 镇痛 ): Fast and potency, effective for various pain(except biliary colic 胆绞痛 ).

Because it is very easy to addiction, ①Only treat to acute megalgia( 急性剧痛 ), such as severe wound, large area of burn, etc.

The aim is to prevent painful shock, but contraindication for shock.

②Treat to pain of later period of cancer also.

Morphine

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(2)Cardiac asthma ( 心源性哮喘 ) (acute ventricular ( 心室 ) failure): Mechanism of therapeutic effects: ①Vasodilatation: Peripheral resistance , and returned blood

volume , heart load . ②Sedation ( 镇静 ) and euphoria (兴奋 ): Alleviating frighten and worry, oxygen

consumption , alleviating anoxia (缺氧 ) of patients.

③Respiratory inhibition: Small dose of morphine slightly inhibit

respiratory center, decrease sensitivity to CO2, let frequency of respiration change from fast and short to slow and deep.

Morphine

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(3)Antidiarrhea(止泻 ): 　 Effective to acute and chronic functional

diarrhea(non-infective). Tincture of opium( 阿片酊 : 1% morphine, 3

% alcohol) or compound tincture of camphor(复方樟脑酊 , 含 5% 的阿片酊 ).

now most in use: Compound diphenoxylate(复方地芬诺酯 , 复方苯乙哌啶 ): content diphenoxylate 2.5 mg, atropine 0.025mg / tablet, 1~2#, po, tid.

(4)Antitussive(止咳 ):

Morphine

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3. Characteristics of ADME: (1)Oral administration(po): ①easy absorption, but fast pass elimination is marked, bioavailability is low(25%);

②therefore, administration by subcutaneous injection(sc) ( 皮下注射 ).

(2)Transportation: ①Morphine is difficultly pass through BBB, but heroin(海洛因 , 二乙酰吗啡 ) very easily pass through BBB;

②easily pass through placenta; ③Morphine is a basic drug, can diffuse from blood to stomach, therefore, can detoxify by gastric lavage (洗胃排毒 ).

Morphine

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4. Adverse reaction: (1)General adverse reactions: Vertigo (眩晕 ), somnolence (睡意 ), slight respiratory inhibition, nausea,

vomiting, constipation, immunosuppression, orthostatic hypotension, retention of urine, biliary colic, etc. (2)Acute toxicity: Acute intoxication/overdose: hypotension, coma ( 昏迷 ), serious respiratory depression, and pin-point pupil.

Acute toxicity can be antagonized by antagonist——Naloxone (纳洛酮 ) or Naltrexone (纳曲酮 ).

Morphine

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(3)Serious adverse reaction: Tolerance, dependence and addiction. Dependence and addiction is the most serious adverse reaction of morphine.

Dependence can be divided into physical dependence and mental dependence.

Physical dependence is a state that develops as a result of the tolerance.

Mental dependence is a state that develops as a result of euphoria (欣快感 ).

Withdrawal syndrome of morphine —— abstinence syndrome(戒断症状 ).

Morphine

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O

N CH3

HO

H3CO

Codeine(可待因 )

Other opioid alkaloids:

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Codeine(可待因 ,  Methylmorphine, 甲基吗啡 )

Its analgesic ( 镇痛 ) effect is 1/10~1/12 of morphine, the antitussive ( 镇咳 ) effect is 1/4 of morphine, therefore, its antitussive is relatively stronger. And its addiction is relatively less. It is mainly used to treat the dry cough (without sputum).  

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(B)Synthetic opioid analgesics

Addiction of opium alkaloids is stronger, therefore, to synthesize opioid analgesics, the addiction is relatively less,

such as: Pethidine ( 哌替啶 ), Fentanyl (芬太尼 ), Methadone (美沙酮 ), Pentazocine (喷他佐辛 ), etc.

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Synthetic opioid analgesics

Pethidine( 哌替啶 , Meperidine, Dolantin, 度冷丁 )

N

O

CH3

O

C2H5 C

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O

N CH3

HO

HO

N

O

CH3

O

C2H5 C

Pethidine

morphine

天然阿片类镇痛药吗啡与人工合成镇痛药哌替啶结构的比较 :

一个叔氮原子 ;

与叔氮相隔两个碳原子的季碳 ;

与季碳相连的苯环 .

Pethidine

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1. Pharmacological effects: The same to morphine, but weaker than

morphine. Potency of analgesic effect is 1/7 ~ 1/10 of

morphine; Analgesic term is shorter than morphine,

about 2~4 hr, the analgesic term of morphine is about 4~6 hr.

Less addiction. The difference to morphine, pethidine has

no effects againt cough and diarrhea.

Pethidine

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2. Clinical uses: (1)Analgesia:　　 Use to treat vary acute severe pain, such

as fracture, burn, pain of cut after operation, and pain of later cancer.

To colic of viscera ( 内脏绞痛 ), such as biliary colic, colic of kidney, ought to administrate with spamolysics together, such as Nitroglycerin(硝酸甘油 ) or Atropine.

Not use to the pain of childbirth. Not use to chronic pain also, because of

avoiding addiction.

Pethidine

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(2)Preanesthetic medication and artificial hibernation ( 人工冬眠 ):

①dispel tension (消除紧张情绪 ), frightened mood of patients before operation, and reduce the dosage of general anesthetics.　② with chlorpromazine(wintermin, 氯丙嗪 ) and promethazine(异丙嗪 ) together compose mixture of hibernation( 人工冬眠合剂 ).

(3)Cardiac asthma: It can be used to treat cardiac asthma replacing morphine.

 

Pethidine

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3. Adverse reactions: (1)Addiction: As morphine, it is easy to addiction too, therefore, it should be strictly controlled to use. (2)Central exciting effect: Normeperidine( 去甲哌啶 ) is the metabolic product of pethadine, with marked central exciting effect, and its t1/2(15~ 20 h) is longer than pethadine(t1/2, 3 h), therefore, it can’t be used for long time.

Pethidine

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 Fentanyl(芬太尼 )

Potent and short-acting of analgesia, the analgesic effect is 100 times than morphine.

im. to take effect in 15 min, maintain 1~2 h, addiction less.

Clinical use: (1)various acute megalgia (剧痛 ); (2)Compatibility with droperidol( 氟哌利多 ), neuroleptic analgesia( 神经松弛镇痛 ), be used to redress wound of large area in burn patients.

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Methadone(美沙酮 ) Potency of analgesic effect is the same as morphine, its effective time is the same as morphine too.

Merits of methadone: (1) Effective by po; (2) Addiction is less than morphine, and appear slower than morphine.

Its abstinence syndrome is lighter, and easier to be treated, therefore, methadone as a surrogate(代用品 ) is used to abstain (戒除 ) addiction in USA .

Abstinence syndrome in 24~48 h after withdraw drug, 3rd day upward to peak, 6~7 weeks later disappear.

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Pentazocine(喷他佐辛 , 镇痛新 ) Analgesic effect is weaker than morphine, about 1/3 of Morphine, but stronger than pethidine, about 3 times of pethidine, there are no addiction almost.

Pentazocine is - and -receptor agonist, -receptor antagonist.

Only use pentazocine, the analgesic effect come from excite -receptor;

Use it with morphine, pentazocine will weaken the analgesic effect of morphine because of blocking -receptor.

Owing to activating -receptor, to cause hallucination ( 幻觉 ), large dose will cause mental disorder, so that it is not encouraged now. 77

Attention The types and nature of pain are the basis of clinical diagnosis.

To severe pain that is not diagnosed clearly, such as acute abdomen( 急腹痛 ), should rapidly find out the causes of illness first, then treat patients with analgesics, in order to avoid covering up the states of illness owing to analgesics, to miss diagnosis of illness and treatment in time.

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(C)Non-opioid analgesics:Rotundin(罗通定 )

Rotundin is levorotatory tetrahydro-palmatine(左旋四氢巴马丁 ), a composition extracted from the stem tuber of a herb named 延胡索 . In addition to analgesic effect, there are sedation ( 镇静 ) and hypnosis ( 催眠 ).

Characteristics of rotundin: 1. Analgesic action is stronger than aspirin and weaker than pethadine.

Used in chronic continuous dull pain, such as headache, dysmenorrhea( 月经痛 ), effective to the pain of GI too.

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2. Used in sedation and hypnosis also, especially suited to insomnia ( 失眠 ) caused by pain.

3. No addiction, no tolerance: Rotundin can be used for long-term.

4. There is no respiratory inhibition in therapeutic dose. 

Adverse reaction: less Occasionally dizziness, weary, nausea, etc.

Rotundin

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(D)Antagonist of opium receptorsNaloxone(纳洛酮 ) & Natrexone(纳曲酮 )

They are antagonist of opium receptor, can block 4 types of opium receptor, itself has no pharmacological effect.

Clinical uses: 1. To treat intoxication of opioid overdose, can eliminate respiratory inhibition in 1~2 minutes, increase respiratory frequency; also be used to treat various respiratory inhibition.

2. Tool agent for study in laboratory; 3. To stimulate addiction breaking up.

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应颂敏应颂敏yings@zju.edu.cnyings@zju.edu.cn 8282

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