Transcript 6-作用于神经系统的药物

Part 8.
Anti-psychiatric disorders
(抗精神失常药)
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Outline
1.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)
Mental
disorders
Schizophrenia√
(精神分裂症)
Psychosis
Mania√
(精神病)
(燥狂症)
Depression√
(抑郁症)
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 TypeⅡ.
hallucination(幻觉), delusion(妄想)
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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
There are 4 neural pathways of
dopaminergic nerve 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.
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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 hypothalamus(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).
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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 heatregulating center (体温调节中枢).
This action is different to antipyretics (解热药).
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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)
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(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.
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(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.
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(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 anticholinergic 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 hepatic22damage, etc.
Chlorprothixene(氯普噻吨,
Tardan, 泰尔登)
Its anti-schizophrenic (精神分裂)
effects is weaker, but with marked antidepression and anti-anxiety (抗焦虑)
effects.
Clinical uses:
used to schizophrenia with anxiety
and anxiety-depression.
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Haloperidol(氟哌啶醇)
Its anti-schizophrenic effects and
extra-pyramidal effects are stronger,
and with stronger effects of antimania(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 longterm.
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 extrapyramidal effect almost.
2. Adverse reaction:
WBC  (granulocytoponia)
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Part 2. Anti-manic and
anti-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 reaction
0.8~1.2 mEq/L Therapeutic concentration
1.6~2.0 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.
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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 anticholinergic effects.
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to depressed patients:
It can elevate mood markedly,
mental stimulation—— marked antidepressive 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 sympathetic 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 antidepressant
effects:
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 antidepressive 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), Paroxetine(帕罗西汀), Sertraline(舍曲林), etc.
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D. Other antidepressants
There are many other antidepressants 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)
(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)
2. Antipyretic, analgesic, and antiinflammatory drugs(解热镇痛抗炎药)
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Part 9. Analgesics
Contents
(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.
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Analgesics
(A)Opium alkaloids:
Opium alkaloids extracted from opium (阿
片);
Opium(阿片) came from poppy(罂粟).
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Analgesics
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.
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Opioid alkaloids
Morphine(吗啡)
HO
O
N
CH 3
HO
Morphine(吗啡)
H3C
OCO
H3C
OCO
Sertürner(German)
extracted from opium in
1806. “Morphine” came
O “morpheus” –
from Greece
–––Greek god of dream
(梦CH3
N
之神).
Heroin(海洛因)
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Morphine
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).
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Morphine
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;
 receptor, 与镇痛无关, 兴奋可引起幻觉, 焦虑和 烦
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躁不安.
Morphine
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.
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Brain
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Peripheral mechanisms of pain
Morphine
sensory neuron
receiving neuron
SP
SP
E
E
CNS
SP
SP
E
opium receptor
neuron contained enkephalin (脑啡肽)
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Morphine
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.
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Morphine
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.
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Morphine
(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).
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Morphine
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).
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Morphine
▲ 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
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directly / large dose.
Morphine
(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, IL10;
TNF(tumor necrosis factor, 肿瘤坏死因子):
TNF-, TNF-, etc.
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Morphine
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.
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Morphine
(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.
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Morphine
(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):
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Morphine
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). 63
Morphine
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
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Naltrexone (纳曲酮).
Morphine
(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).
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Other opioid alkaloids:
Codeine(可待因)
H3CO
O
N
HO
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CH 3
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)
O
C2H5
O
C
N
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CH 3
Pethidine
HO
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:
O
N
CH 3
HO
一个叔氮原子;
morphine
与叔氮相隔两个碳
原子的季碳;
O
C2H5
O
C
与季碳相连的苯环.
N
Pethidine
CH 3
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Pethidine
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.
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Pethidine
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.
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Pethidine
(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.
②with 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.
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Pethidine
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.
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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.
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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 tetrahydropalmatine(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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Rotundin
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.
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(D)Antagonist of opium receptors
Naloxone(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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THANK YOU!!!
应颂敏
[email protected]
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