神经系统药理 5 一、抗精神病药和抗抑郁药二、麻醉药

神经系统药理 5

一、抗精神病药和抗抑郁药二、麻醉药

一、抗精神病药和抗抑郁药 Antidepressant and antimanic drugsAntidepressant and antimanic drugs

抗抑郁和抗躁狂药抗抑郁和抗躁狂药 Anxiolytics / antianxieticsAnxiolytics / antianxietics

抗焦虑药抗焦虑药 Antipsychotic drugsAntipsychotic drugs

抗精神分裂药抗精神分裂药

Disorders of mood Disorders of mood ((affective disordersaffective disorders 情感障碍情感障碍 )) are are extremely common in medical practice. The severity extremely common in medical practice. The severity of these conditions covers an extraordinarily broad of these conditions covers an extraordinarily broad range, from normal grief(range, from normal grief( 悲伤悲伤 ) reactions and ) reactions and dysthymia(dysthymia( 心境恶劣心境恶劣 ) to severe, incapacitating illness ) to severe, incapacitating illness that may result in death.that may result in death.

EmotionEmotion （情绪）（情绪） refers to transient responses to refers to transient responses to environmental, internal, and cognitive stimuli, while environmental, internal, and cognitive stimuli, while moodmood （心境）（心境） refers to the predominant emotional refers to the predominant emotional state over time.state over time.

Disorders of MoodDisorders of Mood

The symptoms of The symptoms of depressiondepression are intense feelings of are intense feelings of sadness, hopelessness, despair, and inability to sadness, hopelessness, despair, and inability to experience pleasure in usual activity.experience pleasure in usual activity.

ManiaMania is characterized by the opposite behavior, is characterized by the opposite behavior, that is, enthusiasm, rapid thought and speech that is, enthusiasm, rapid thought and speech patterns, and extreme self-confidence and impaired patterns, and extreme self-confidence and impaired judgment.judgment.

AnxietyAnxiety, a state characterized by arousal, vigilance, , a state characterized by arousal, vigilance, physiologic preparedness, and negative subjective physiologic preparedness, and negative subjective states, may share certain critical circuits with states, may share certain critical circuits with fearfear..

Disorders of MoodDisorders of Mood

Monoamine hypothesis of DepressionMonoamine hypothesis of Depression （单胺假说）（单胺假说）

5-HT 5-HT — genetic basis of depression & mania — genetic basis of depression & mania

NE NE — — depressiondepression

NE NE — — maniamania

Modulation of monoamines in the synaptic space Modulation of monoamines in the synaptic space and/or the related post-synaptic receptors is of and/or the related post-synaptic receptors is of therapeutic importancetherapeutic importance

Long-term adaptations to antidepressant treatmentLong-term adaptations to antidepressant treatment

Classes of Antidepressants

Tricyclic Antidepressants (TCAs)

Monoamine Oxidase Inhibitors (MAOIs)

Norepinephrine Reuptake Inhibitors (NARIs)

Selective Serotonin Reuptake Inhibitors (SSRIs)

Serotonin and Norepinephrine Reuptake

Inhibitors (SNRIs)

Noradrenergic and specific serotonergic

antidepressants (NaSSAs)

Model of the neurotrophic Model of the neurotrophic hypothesis ofhypothesis ofantidepressant treatments and antidepressant treatments and stress-related disordersstress-related disorders

Imipramine Imipramine 丙米嗪丙米嗪（米帕明）（米帕明）

N

CH2CH2CH2NCH3

CH3

Tricyclic Tricyclic structurestructure

A.A. Antidepressant Drugs Antidepressant Drugs

Tricyclic Antidepressants (TCAs)

丙咪嗪

阿米替林

氯丙咪嗪

多塞平

临床应用副作用

1. 1. Pharmacological effectsPharmacological effects

(1) Central effects(1) Central effects Inhibiting reuptake of monoamine transmittersInhibiting reuptake of monoamine transmitters Improving patient’s mood after 2 weeksImproving patient’s mood after 2 weeks Sedative effects in normal subjects (anti-Sedative effects in normal subjects (anti-

histaminergic or histaminergic or -adrenergic blocking -adrenergic blocking properties)properties)

(2) Autonomic effects(2) Autonomic effects Muscarinic blocking effectsMuscarinic blocking effects

(3) Cardiovascular effects(3) Cardiovascular effects Hypotension, tachycardia, arrhythmiaHypotension, tachycardia, arrhythmia


2. 2. Clinical usesClinical uses

(1) Depression(1) Depression

Endogenous, melancholic, Endogenous, melancholic, etc.etc.

(2) Enuresis(2) Enuresis (( 遗尿遗尿 ))

(3) Anxiety (3) Anxiety (( 焦虑焦虑 )) and panic disorder and panic disorder (( 惊恐惊恐症症 ))


3. 3. Adverse effectsAdverse effects

(1) Antimuscarinic effects(1) Antimuscarinic effects dry mouth, constipation(dry mouth, constipation( 便秘便秘 ), intraocular pressure ), intraocular pressure

increase, blurred vision, urinary retention, increase, blurred vision, urinary retention, etc.etc.

Contraindicated in prostatauxe and glaucomaContraindicated in prostatauxe and glaucoma

(2) CNS reactions(2) CNS reactions Confusion or delirium(Confusion or delirium( 谵妄谵妄 ), depression-mania (bipolar ), depression-mania (bipolar

patients)patients)

(3) CVS reactions(3) CVS reactions Postural hypotension, sinus tachycardia, potential of Postural hypotension, sinus tachycardia, potential of

arrhythmiaarrhythmia


4. 4. Drug interactionsDrug interactions

(1) Plasma protein binding(1) Plasma protein binding displacement by phenytoin, aspirin, scopolamine(displacement by phenytoin, aspirin, scopolamine( 东莨菪东莨菪

碱碱 ), phenothiazines (), phenothiazines ( 吩噻嗪类吩噻嗪类 ), ), etc. etc.

(2) MAO inhibitors(2) MAO inhibitors potentiating the effects of TCA,potentiating the effects of TCA,

contraindicated for combination with MAOIscontraindicated for combination with MAOIs

(3) Potentiating the effects of CNS depressant drugs(3) Potentiating the effects of CNS depressant drugs


Interaction of TCA with other types of drugs Interaction of TCA with other types of drugs


Monoamine oxidase inhibitors Monoamine oxidase inhibitors ((MAOIsMAOIs))

Selective for central MAO-B, less selective for enteric Selective for central MAO-B, less selective for enteric MAO-A; MAO-A;

Used in treatments of depression (non-sensitive to Used in treatments of depression (non-sensitive to TCAs) and Parkinson diseaseTCAs) and Parkinson disease

phenelzinephenelzine (( 苯乙肼苯乙肼 ): non-selective): non-selective

selegilineselegiline (( 司来吉兰司来吉兰 ): also used in Parkinson disease): 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 inhibition results in hypertension, headache, palpitations, nausea, vomiting

Tyramine is present in a number of foodstuffs, such as aged cheese, red wine, etc.


NE reuptake inhibitors NE reuptake inhibitors ((NRIsNRIs)) Selective norepinephrine reuptake inhibitsSelective norepinephrine reuptake inhibits rapid actionsrapid actions weaker sedative, anticholinergic and hypotensive effectsweaker sedative, anticholinergic and hypotensive effects

desipramine desipramine (( 地昔帕明地昔帕明 ))

maprotiline maprotiline (( 马普替林马普替林 ))

nortriptyline nortriptyline (( 去甲替林去甲替林 )) protriptylin protriptylin (( 普罗替林普罗替林 ))

amoxapine amoxapine (( 阿莫沙平阿莫沙平 ))


Selective 5-HT reuptake inhibitorsSelective 5-HT reuptake inhibitors Selective serotonin reuptake inhibits (SSRIs)Selective serotonin reuptake inhibits (SSRIs) weaker sedative effectsweaker sedative effects with anti-anxiety effectswith anti-anxiety effects

fluoxetine fluoxetine (( 氟西汀，百氟西汀，百忧忧解解 )) ：抑郁症、神经性贪食症：抑郁症、神经性贪食症 paroxetine paroxetine (( 帕罗西汀帕罗西汀 ))

sertraline sertraline (( 舍曲林舍曲林 ))


5-HT/NE reuptake inhibitors5-HT/NE reuptake inhibitors Mixed serotonin/norepinephrine reuptake inhibits Mixed serotonin/norepinephrine reuptake inhibits

(SNRIs)(SNRIs) rapid action rapid action less affinity with receptors less affinity with receptors higher safetyhigher safety

venlafaxine venlafaxine (( 文拉法辛文拉法辛 ))

milnacipram milnacipram (( 米那普仑米那普仑 )) lofepramine lofepramine (( 洛夫帕明洛夫帕明 ))

A.A. Antidepressant Drugs Antidepressant DrugsNoradrenergic and specific serotonergic Noradrenergic and specific serotonergic

antidepressantantidepressant (NaSSA) (NaSSA) mirtezapine mirtezapine (( 米氮平米氮平 ))

blockingblocking presynapticpresynaptic (auto- or hetero-) (auto- or hetero-) 22 receptor receptor on both on both

norepinephrine and serotonin (5-HT) pre-synaptic axonsnorepinephrine and serotonin (5-HT) pre-synaptic axons

- increasing NE and 5-HT release- increasing NE and 5-HT release;; stimulating postsynaptic stimulating postsynaptic 11 receptors receptors on serotonergic cell bodies on serotonergic cell bodies

- increasing the firing rate of serotonergic neurons- increasing the firing rate of serotonergic neurons potently blocking postsynaptic 5-HTpotently blocking postsynaptic 5-HT2A2A, 5-HT, 5-HT2C2C and 5-HT and 5-HT33

receptors receptors – attenuating 5-HT– attenuating 5-HT2C2C-mediated anxiety-mediated anxiety

The net outcome of these effects isThe net outcome of these effects is ：： increased increased noradrenergicnoradrenergic activity activity

increased increased serotonergic activityserotonergic activity, esp. 5-HT, esp. 5-HT1A1A receptors receptors

B.B. Antimanic Drugs Antimanic Drugs

Lithium carbonateLithium carbonateCarbamazepine Carbamazepine ChlorpromazineChlorpromazineOther related antiepileptic Other related antiepileptic

and antipsychotic drugs and antipsychotic drugs


1. 1. Pharmacological effects and clinical usesPharmacological effects and clinical uses

Mood-stabilizing agentMood-stabilizing agent

(1) Inhibiting NE and DA release(1) Inhibiting NE and DA release

(2) Interfering phosphatidylinositol (PI) metabolism(2) Interfering phosphatidylinositol (PI) metabolism

(3) Substitute for sodium in generating action potentials and (3) Substitute for sodium in generating action potentials and in Nain Na++-K-K++ exchange across the membrane. exchange across the membrane.

Lithium carbonate Lithium carbonate 碳酸锂碳酸锂


Related to the serum concentration of LiRelated to the serum concentration of Li++

0.8 – 1.5 mmol/L:0.8 – 1.5 mmol/L: therapeutic leveltherapeutic level 1.6 – 2.0 mmol/L:1.6 – 2.0 mmol/L: GI reactionsGI reactions > 2.0 mmol/L:> 2.0 mmol/L: CNS toxicityCNS toxicity

Monitoring serum concentration of LiMonitoring serum concentration of Li++ if if possiblepossible


(1) Side effects(1) Side effects Nausea, vomiting, abdominal pain, diarrhea, Nausea, vomiting, abdominal pain, diarrhea,

sedation, finger tremor, polyuria, sedation, finger tremor, polyuria, etc.etc.

(2) Acute intoxication(2) Acute intoxication Mental confusion, coma, hyperreflexia(Mental confusion, coma, hyperreflexia( 反射亢进反射亢进 ), ),

gross tremor, dysarthria(gross tremor, dysarthria( 构音困难构音困难 ), seizures, ), seizures, etc.etc.

(3) Others (3) Others Benign thyroid enlargement, renal damageBenign thyroid enlargement, renal damage


C.C. Anxiolytic drugs Anxiolytic drugs

1. Benzodiazepines 1. Benzodiazepines see details in Ssee details in Sedative-Hypnotic Drugsedative-Hypnotic Drugs

2. Buspirone2. Buspirone （丁螺环酮）（丁螺环酮）

5-HT5-HT1A 1A receptor selective partial agonist, lowering receptor selective partial agonist, lowering

5-5-HT releaseHT release Fewer sedative, hypnotic, memory-deficient effectsFewer sedative, hypnotic, memory-deficient effects No cross tolerance to benzodiazepines, and less No cross tolerance to benzodiazepines, and less

potential of dependencepotential of dependence

Schizophrenia(精神分裂症 )

• Neurological Disorder - impairs ability to

perceive, understand & interpret the environment

• Impaired social and occupational function

• Behavioral Syndrome – predictable or not

• Etiology and biology remain unclear- familial

tendency, DA and other neurotransmitters

• History – early dementia, unremitting bad course

Signs & Symptoms

Positive symptoms• Delusions ( 妄想 ) - fixed false belief outside

cultural norm (bizarre vs. non bizarre)• Hallucinations ( 幻觉 ) - perceptual (hearing),

have no outside source • “Like my voice”• Not an illusion (a mistaken perception for which there is

an actual external stimulus)

• Disorganization ( 思维紊乱 ) - pattern of speech or behavior, making up words without a meaning (neologisms)

Negative symptoms• Affective flattening• Avolition / Amotivation (decreased motivation)• Autistic(孤独 ) behaviors (social withdrawal )• Anhedonia (inability to experience pleasure )• Ambivalence (coexistence of opposing attitudes or

feelings，矛盾心态 ) • Anosognosia (疾病感缺失 ) (impaired awareness

of illness )

Signs & Symptoms

1. Phenothiazines1. Phenothiazines （吩噻嗪类）（吩噻嗪类） Chlorpromazine 氯丙嗪氯丙嗪 perphenazine perphenazine 奋乃静；奋乃静； fluphenazine fluphenazine 氟奋乃静氟奋乃静 trifluoperazine trifluoperazine 三氟拉嗪；三氟拉嗪； thioridazine thioridazine 硫利达嗪硫利达嗪

2. Thioxanthenes (2. Thioxanthenes ( 硫杂蒽类硫杂蒽类 )) Chlorprothixene 氯普噻吨（泰尔登）

3. Butyrophenones3. Butyrophenones （丁酰苯类）（丁酰苯类） Haloperidol 氟哌啶醇 Droperidol 氟哌利多（氟哌啶）

Classified according to chemical structures

D.D. Antipsychotic drugs Antipsychotic drugs

Typical antipsychotic drugs are dopamine DTypical antipsychotic drugs are dopamine D22 receptor antagonists receptor antagonists

• Typical

OthersOthers

PenfluridolPenfluridol 五氟利多五氟利多 Longer duration of action, taking once weeklyLonger duration of action, taking once weekly

SulprideSulpride 舒必利舒必利 selectively acts on mesolimbic Dselectively acts on mesolimbic D22 receptors receptors

few extrapyramidal reactions few extrapyramidal reactions

ClozapineClozapine 氯氮平氯氮平 Blocking DBlocking D44 and 5-HT receptors and 5-HT receptors

RisperidoneRisperidone 利培酮利培酮 Blocking Blocking DD22 and 5-and 5-HTHT22 receptors receptors

Actions of some Actions of some secondary generation secondary generation drugsdrugs

• Atypical


High potency Low potency

螺环哌啶酮

苯哌利多三氟哌啶醇

氟哌利多

普马嗪

D.D. Antipsychotic drugs Antipsychotic drugs• The dopamine hypothesis of schizophrenia

• The serotonin hypothesis of schizophrenia

• The glutamate hypothesis of schizophrenia

PhenothiazinesPhenothiazines （吩噻嗪类）（吩噻嗪类）

Chlorpromazine Chlorpromazine 氯丙嗪氯丙嗪

N

S

(CH2)3

Cl

N(CH3)2


1. 1. Pharmacological effectsPharmacological effects

(1)(1)Central effects:Central effects:Blocking central DBlocking central D22 dopamine receptors dopamine receptorsa) Antipsychotic effects (neuroleptic effects)a) Antipsychotic effects (neuroleptic effects) for treatment of for treatment of schizophreniaschizophrenia controlling excitation and then hallucinations (weeks to controlling excitation and then hallucinations (weeks to

months)months)b) Antiemetic effects(b) Antiemetic effects( 镇吐作用镇吐作用 )) inhibiting inhibiting chemoreceptor trigger zonechemoreceptor trigger zone (CTZ) dopaminergic (CTZ) dopaminergic

functionfunctionc) Poikilothermic effects (c) Poikilothermic effects ( 体温调节作用体温调节作用 )) hypothermic anesthesiahypothermic anesthesia artificial hibernation (artificial hibernation ( 人工冬眠人工冬眠 ))d) Extrapyramidal effectsd) Extrapyramidal effects primary adverse effectsprimary adverse effectse) Potentiating the effects of central depressantse) Potentiating the effects of central depressants sedative-hypnotics, analgesics, general anesthetics, ethanolsedative-hypnotics, analgesics, general anesthetics, ethanol


(2) Autonomic nervous system effects(2) Autonomic nervous system effects

a) Hypotensive effectsa) Hypotensive effects receptor blockade, receptor blockade, postural hypotensionpostural hypotension

b) Anticholinergic effectsb) Anticholinergic effects dry mouth, constipation, blurred vision, urinary dry mouth, constipation, blurred vision, urinary

retention, etc.retention, etc.

(3) Endocrine effects(3) Endocrine effects prolactin prolactin ACTH, growth hormone ACTH, growth hormone


2. 2. Clinical usesClinical uses

(1) Treatment of schizophrenia(1) Treatment of schizophrenia

(2) Treatments of emesis and hiccough(2) Treatments of emesis and hiccough

used forused for emesis emesis （止吐）（止吐） andand hiccoughhiccough （呃逆）（呃逆） but ineffective on motion sicknessbut ineffective on motion sickness

(3) Hypothermic anesthesia ((3) Hypothermic anesthesia (combined with lowering room combined with lowering room

temperaturetemperature)) and artificial hibernation ( and artificial hibernation (combined with combined with

Pethidine Pethidine 哌替啶哌替啶 and promethazineand promethazine 异丙嗪异丙嗪 ))



(1) Side effects(1) Side effects

Central depressionCentral depression

Peripheral effects:Peripheral effects: postural hypotensionpostural hypotension, , dry mouth, and other effects resulting from dry mouth, and other effects resulting from muscarinic and muscarinic and receptor blockade receptor blockade


(2) Extrapyramidal effects(2) Extrapyramidal effects

Due to DA receptor block:Due to DA receptor block: a) Parkinsonisma) Parkinsonism

b) Akathisia (b) Akathisia ( 静坐不能静坐不能 ))

c) Acute dystonia (c) Acute dystonia ( 急性肌张力障碍急性肌张力障碍 ))

attenuated by central muscarinic antagonistsattenuated by central muscarinic antagonists

Due to supersensitive to DA:Due to supersensitive to DA:

Tardive dyskinesiaTardive dyskinesia (( 迟发性运动障碍迟发性运动障碍 ))


(3) Other central reactions(3) Other central reactions neuroleptic maglinant syndrome neuroleptic maglinant syndrome (( 神经阻滞药神经阻滞药

恶性综合征）恶性综合征） psychotic reactions psychotic reactions (( 药源性精神异常药源性精神异常 ))

epilepsy and convulsion: lowering seizure epilepsy and convulsion: lowering seizure thresholdthreshold

(4) Allergic and hemological reactions(4) Allergic and hemological reactions

skin reactions, leukopenia, skin reactions, leukopenia, obstructive obstructive jaundice, jaundice, liver damageliver damage


(5) CVS reactions (5) CVS reactions

arrhythmiaarrhythmia

hypotension: treated byhypotension: treated by receptor agonists receptor agonists sudden death (elderly with CVS diseases)sudden death (elderly with CVS diseases)

(6) Endocrine reactions(6) Endocrine reactions hyperplasia of mammary glands (hyperplasia of mammary glands ( 乳腺增生乳腺增生 ), ),

galactorrhea (galactorrhea ( 溢乳溢乳 ), amenorrhea (), amenorrhea ( 闭经闭经 ),),

child growth retard(child growth retard( 生长抑制生长抑制 ))


(6) Acute intoxication(6) Acute intoxication

severe CNS depression, coma, severe hypotensionsevere CNS depression, coma, severe hypotension

(7) Contraindications(7) Contraindications epilepsyepilepsy comacoma elderly with CVS disorderselderly with CVS disorders severe hepatic and renal dysfunctionsevere hepatic and renal dysfunction


Other phenothiazinesOther phenothiazines

perphenazine perphenazine 奋乃静奋乃静

fluphenazine fluphenazine 氟奋乃静氟奋乃静

trifluoperazine trifluoperazine 三氟拉嗪三氟拉嗪

thioridazine thioridazine 硫利达嗪硫利达嗪

more potent therapeutic effects and more potent therapeutic effects and extrapyramidal effectsextrapyramidal effects


Thioxanthenes Thioxanthenes (( 硫杂蒽类硫杂蒽类 ))

ChlorprothixeneChlorprothixene 氯普噻吨（泰尔登）氯普噻吨（泰尔登）

Used for the patients with symptoms of Used for the patients with symptoms of depressiondepression and and anxietyanxiety


ButyrophenonesButyrophenones （丁酰苯类）（丁酰苯类）

Haloperidol Haloperidol 氟哌啶醇氟哌啶醇

Droperidol Droperidol 氟哌利多（氟哌啶）氟哌利多（氟哌啶）

Combined with fentanyl:Combined with fentanyl: neuroleptanalgesianeuroleptanalgesia （神（神经安定经安定 [[ 镇痛镇痛 ] ] 麻醉术）麻醉术）


OthersOthers Penfluridol Penfluridol 五氟利多五氟利多 Longer duration of action, taking once weeklyLonger duration of action, taking once weekly

Sulpride Sulpride 舒必利舒必利

selectively acts on mesolimbic Dselectively acts on mesolimbic D22 receptors receptors

few extrapyramidal reactions few extrapyramidal reactions

Clozapine Clozapine 氯氮平氯氮平

Blocking DBlocking D44 and 5-HT receptors and 5-HT receptors

Risperidone Risperidone 利培酮利培酮

Blocking Blocking DD22 and 5-and 5-HTHT22 receptors receptors


局部麻醉药

Local Anesthetics (LAs)

Definition: drugs that cause loss of sensation

without loss of consciousness

Reversibly block nerve conduction

Act on every type of nerve fiber

Also act on cardiac muscle, skeletal muscle and the brain

No structural damage to the nerve cell

可卡因

普鲁卡因

丁卡因

苯佐卡因

all are weak basesBH+ B + H+

Structural Classes: Esters and Amides

利多卡因

甲哌卡因

布比卡因

布比卡因

丙胺卡因

Use-dependent Blockade

Actions of LAs

Ionic gradient and resting membrane potential are unchanged

Decrease the amplitude of the action potential

Slow the rate of depolarization

Increase the firing threshold

Slow impulse conduction

Prolong the refractory period

CNS Toxicity

Correlation between potency and seizure threshold Bupivacaine

• 2 ug/ml Lidocaine

• 10 ug/ml

Cardiovascular ToxicityAttributable to their direct effect on cardiac muscle

Contractility Negative inotropic effect that is dose-related and

correlates with potency

Interference with calcium signaling mechanisms

Automaticity Negative chronotropic effect

Rhythmicity and Conductivity Ventricular arrhythmias

Absorption (injected or topical)

- affected by vascularity ( 血供 )

- presence of additional vasoconstrictor ( 血管收缩剂 )

- Duration prolonged by vasoconstrictor (epinephrine)

- localizes agent to site of action

- contraindicated in extremities( 末梢部位 )

- Systemic Toxic Effects: CNS, cardiovascular

Pharmacokinetics

Alpha phase ( 快速吸收相 ) – rapidly redistributed to well-perfused tissues

Beta phase ( 再分布相 ) – distribution to less perfused or slowly equiliibrating tissues

Gamma phase ( 消除相 ) – clearance representing metabolism and excretion

Distribution- LAs bind in the blood to a1-glycoprotein and albumin

Pharmacokinetics

Uses of local anesthesia / Modes of Administration

•Topical local (surface) anesthesia( 表面麻醉 ): for eye, ear, nose, and throat procedures and for cosmetic surgery

•Infiltration anesthesia ( 浸润麻醉 ): local injection around the region to be operated.

•Conduction anesthesia ( 传导麻醉 ): local injection around the peripheral nerve trunk

•Epidural ansthesia ( 硬膜下麻醉 ): local injection into the epidural space

•Subarachnoid anesthesia ( 蛛网膜下腔麻醉 ): or Spinal anesthesia ( 脊髓麻醉，腰麻 ): local injection into

the cerebrospinal fluid in subarachnoid cavity

Adverse reactions

Toxicity: CNS, CVS

Allergic Reactions

Metabolite of “ester” LAs Para-aminobenzoic acid

Allergen

Allergy to “amide” LAs is extremely rare

Lidocaine

One of the most widely used local anesthetics

Rapid onset, medium duration

Also available in ointment （软膏） , jelly （凝胶） , and aerosol （喷雾剂）

Other uses: anti-arrhythmic

Eutectic Mixture of Local Anesthetic (EMLA)

Contains lidocaine (2.5%), prilocaine (丙胺卡因 2.5%), emulsifier 乳化剂 , thickener 增稠剂 , distilled water

(a eutectic mixture has a melting point below room temperature and therefore both local anesthetics exist as a liquid oil rather than as crystals)

Must be applied one hour prior to procedure

全身性麻醉剂全身性麻醉剂

WHAT IS General ANESTHESIA ? Anesthesia is necessary for some diagnostic, therapeutic, and

surgical intervention

The physiologic state induced by general anesthetics

typically includes analgesia, amnesia, loss of consciousness,

inhibition of sensory and autonomic reflexes, and skeletal

muscle relaxation.

Types of General Anesthesia :

Inhaled Anesthetics (gases or “vapors”)

Intravenous Anesthetics (be given intravenously).

Inhaled anesthetics( 吸入麻醉药 )Many different, apparently unrelated

molecules produce general anesthesia – inert gases, simple inorganic & organic compounds, more complex organic compounds

Characteristics – rapid onset, rapid reversibility, relationship between lipid solubility & potency

Stages of anesthesia (ether)

Stage I: analgesia – sensory block in spinal cord

Stage II: paradoxical excitation due to loss of some inhibitory tone and direct stimulation of excitatory transmission

Stage III: surgical anesthesia – block of the ascending reticular activating system

Stage IV: failure – cardiovascular and respiratory collapse due to inhibition

Signs for anesthetic depth

TachycardiaHypertension Eyelid reflexLacrimationSwallowingLaryngospasmMovement

TOO LIGHT TOO DEEP

• Hypotension• Organ failure

Nitrous Oxide

N NO

Gas at room temperature

C C

F

F

F O

H

C

F

F

H

F

C C

ClF

F

F O

H

C

F

F

H

C C H

Cl

Br

F

F

F

C C O

H

C

H

CH

H

H H

H H

H

HDiethyl Ether

( 乙醚 )

Volatile liquids at room temperature

Halothane( 氟烷 )

Isoflurane( 异氟醚 )

Desflurane( 地氟醚 )

Inhaled anesthetic delivery system

Vaporizing the anesthetic liquid

Gas flowmeters

Mask

Higher blood solubility is shown as a larger blood box Higher solubility means gas rapidly moves into blood, but

concentration that reaches brain increases more slowly

Blood:gas partition coefficient:an index for solubility

Brain:Blood Partition Coefficient

MAC –minimum alveolar anesthetic concentration

MAC is the anesthetic concentration that produces

immobility in 50% of patients exposed to a noxious stimulus.

Addition of MAC

Factors that alter MAC

Increase MAC – Being young, hyperthermia, chronic ETOH, CNS stimulants, hyperthyroidism

Decrease MAC – Old age, hypothermia, acute ETOH, CNS depressant drugs including narcotics & benzodiazepines

General characteristicsAnalgesia – weak except for nitrous oxide

Potency – high, except for nitrous oxide

Muscle Relaxation – some, but weak

Airway irritation – desflurane ( 地氟醚 ) worst, sevoflurane ( 七氟烷 ) best tolerated

Primary effect on conductive tissue – inhibitory

Primary effect on smooth muscle – relaxation

Effects on brain

Transition to unconsciousness 0.4 MAC O2 consumption but Cerebral Blood Flow means potential injury with

brain tumors/head injury (↑ pressure)

Effects on ventilation

Respiratory Rate; Tidal Volume

Ventilation; PaCO2; Hypoxia Risk

Liver toxicity

“Halothane Hepatitis”

Incidence post Halothane – 0.003%

Symptoms – fever, anorexia( 胃口不好 ), nausea & vomiting that occur 2 - 5 days post-op

Blood – eosinophilia; altered liver function

Rare – liver failure & death

Malignant hyperthermia

Hypermetabolic syndrome – 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 from 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 apoptosisEarly apoptosis

Late apoptosisLate apoptosis

control

exposed

Intravenous Anesthetics( 静脉麻醉药 )Usually activate GABAA receptors

硫喷妥

异丙酚依托咪酯

氯胺酮

咪达唑仑

Redistribution of thiopental after an intravenous bolus administration 硫喷妥

Combination of Anesthetics (复合麻醉 )

PremedicationBasal anesthesiaInduction of anesthesiaskeletal muscle relaxantsNeuroleptanesthesia (NLA,神经安定镇痛术 )

See you next class!See you next class!

Documents

神经系统药理 5 一、 抗精神病药和抗抑郁药 二、麻醉药

神经系统药理 5 一、抗精神病药和抗抑郁药二、麻醉药