Drugs that act in the central nervous system
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Drugs that act in the central nervous system (1). Introduction to the pharmacology of CNS drugs. Cortex ( 皮质 ). evolutionally formed last receiving and processing information, control of sight, listening, movement, memory, wake, autonomic function. Limbic system ( 边缘系统 ).

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Drugs that act in the central nervous system (1)

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Drugs that act in the central nervous system

(1)


Introduction to the pharmacology of CNS drugs


Cortex(皮质)

  • evolutionally formed last

  • receiving and processing information, control of sight, listening, movement, memory, wake, autonomic function


Limbic system(边缘系统)

A group of interconnected deep brain structures, common to all mammals, and involved in olfaction, emotion, motivation, behavior, and various autonomic functions.


limbic system边缘系统:

hippocampus海马、amygdala杏仁、septal area膈区、basal ganglia基底节


Cerebellum(小脑)

responsible for the regulation and coordination of complex voluntary muscular movement as well as the maintenance of posture and balance.

The cerebellum has been reported to play a role in psychiatric conditions such as schizophrenia, autism, mood disorders, dementia, and attention deficit hyperactivity disorder(ADHD).


Diencephalon(间脑)

The diencephalon is a complex of structures within the brain, whose major divisions are the thalamus and hypothalamus. It functions as a relay system between sensory input neurons and other parts of the brain, as an interactive site for the central nervous and endocrine systems, and works in tandem with the limbic system.


thalamus


thalamus


central part of the brain, under the cortex and basal ganglion and above the hypothalamus

relay station of senses


hypothalamus下丘脑 :integrative area of autonomic nerve

regulation of temperature, water balance, metabolism, blood pressure, circadian rhythm, sex activity, sleeping, etc


hypothalamus


Midbrain and brain stem:

中脑


tegmentum(被盖),ascending reticular activating system, NTS, area postrema

regulation of sleeping, wake, eye movement, vomiting, cardiovascular and respiratory reflex


Spinal cord脊髓:

pathways of senses and movement;autonomic reflex


Neuropathway?


mesolimbic pathway: memory and motivating behaviors

mesocortical pathway: thinking and schizophrenia

nigrostriatal pathway: motor control

tuberoinfundibular pathway: hormones secretion


Cellular organization of the brain

1012 neurons

1014 synapses

complex net


Ion channels and receptors

1, voltage-gated channels: fast responses

2, ligand-gated channels (ionotropic receptors 离子型受体)

3,metabotropic receptors(促代谢型受体), G protein related, indirectly modulate the voltage-gated channels: slow, diversity


:


The synapse and synapse potentials


Pre-synaptic action potential→voltage-sensitive calcium channels → Ca2+ into the terminals → transmitter release → acting at the receptors post-synaptically → EPSP or IPSP


Sites of drug action

1, presynaptic action potential

2, synthesis

3, storage 7, degradation

4, metabolism 8, receptor

5, release 9, ionic conductance

6, reuptake


Cellular organization of the brain

1012 neurons

1014 synapses

complex net


neurotransmitters at central synapses

Ach: acetylcholine

NA: noradrenaline

DA: dopamine

5-HT: serotonin; 5-hydroxytrptamine

GABA: γ-aminobutyric acid

glutamate


Opioid peptides 阿片样肽

Histamine 组胺

Prostaglandins 前列腺素

Tackykinins 速激肽

Glycine 甘氨酸

Adenosine 腺苷


Modulators 调质: to modulate the response of a neuron to a neurotransmitter or hormone

Transmitter and modulator, action changeable sometimes


Chapter 11 General anesthetics

全身麻醉药

General anaesthesia全麻: a state characterized by unconsciousness, analgesia, amnesia, skeletal muscle relaxation and loss of reflexes.

different from pain relieving


Any other method for pain-relieving for operation?


  • 针灸、冷冻

  • 公元前五世纪(战国时代):扁鹊,记载中药麻醉,无从考证

  • 公元前二世纪,华陀,麻沸散刮骨疗毒;曼陀罗主要成分东莨菪碱,中枢抑制作用

  • 十九世纪中叶前,国外放血造成休克昏迷行手术;压迫肢体致发麻、冷冻止痛

  • 十九世纪三十年代,国外捆绑或抓住病人进行手术

  • 太监,醉酒,或敲头致昏


inhaled anesthetics

  • enflurane(恩氟烷), isoflurane(异氟烷), desflurane(地氟烷), sevoflurane(七氟烷), nitrous oxide(氧化亚氮)

  • ether(乙醚), cyclopropane(环丙烷) flammable, no longer used clinically now


O

O

N

N

N

Nitrous oxide

氧化亚氮

(笑气)

Nitric oxide

一氧化氮

(递质)


  • airway→alveoli →blood →brain

  • airway←alveoli ←blood ←brain


blood:gas partition coefficient

blood/gas partition coefficient is the ratio of the amount dissolved in blood to the amount in the same volume of gas in contact with that blood.

The more blood-soluble the agent (high blood-gas partition coefficient), the slower the onset of effect and the slower the patient goes to sleep

new inhaled anesthetics have low partition coefficient


MAC(minimum alveolar concentration):the anesthetic concentration that produces immobility in 50% of patients exposed to a noxious stimulus.


mechanism

To be demonstrated

action: depressing spontaneous and evoked activity of neurons


Advantages of inhaled anesthetics:

 short induction period (in seconds)

 almost no local irritation and side effects

 satisfactory muscular relaxation

 recovery fast

easy to adjust depth of anesthesia


Enflurane 恩氟烷


Enflurane


Sevoflurane


Sevoflurane (Sevorane)


Clinical uses: combined use with intravenous anesthetics for operation anesthesia


Intravenous anesthetics

Intravenous anesthetics: thiopental, midazolam, opioid anagesics, propofol, ketamine

Clinical uses:

1, induction of anesthesia

2, small operation when used only


Thiopental sodium

(硫喷妥钠)

widely used in the middle of last century; rapid intravenous administration may lead to inhibition of breathing


氯胺酮


ketamine:

抑制丘脑- 新皮质系统, 选择性地阻断痛觉

对大脑边缘系统具有兴奋作用

“意识与感觉的分离”

dissociative anaesthesia 分离麻醉

麻醉作用快、镇痛强

短时手术麻醉剂;麻醉诱导剂

战场急救


“K粉”、“俱乐部药”、“舞会药”

100 mg:产生自我感觉良好的、幻觉的、漂浮的、知觉轮换和扩张的感觉

2004.7 SFDA 一类精神药品管理


依托咪酯、丙泊酚、瑞芬太尼

临床应用较多


Concepts of combined anesthesia

麻醉前给药

基础麻醉

诱导麻醉

低温麻醉

控制性降压


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