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Section 4
Drugs Affecting the Center
Nervous System
Department of Pharmacology
Chapter 22
Sedative and hypnotic
Drugs
Definitions
 A sedative drug decreases activity,
moderates excitement, and calms the
recipient.
 A hypnotic drug produces drowsiness
and facilitates the onset and maintenance
of a state of sleep that resembles natural
sleep, and from which the patient can be
easily aroused.
Drugs:
 Benzodiazepines (BDZs)
 Barbiturates
 Others: chloral hydrate
Small dose: sedation
Large dose: hypnosis; anticonvulsant;
anesthesia
苯二氮卓类 (Benzodiazepines BZ)
地西泮（安定）
Diazepam
奥沙西泮
Oxazepam
三唑仑
Triazolam
Drugs
Diazepam
Oxazepam
Triazolam
Elimination
half life
(hours)
30~60
Dosage（mg）
sedative
hypnoti
c
2.5~5
,tid
5~10
5~10
15~30,
qd,tid
15~30
1.5~3
-
0.25~0.5
（15~30分
起效)
Diazepam 地西泮
（valium, 安定）
Action and use:
 Reduction of anxiety
The anxiolytic actions can be occurred at
lower dosage .
lose memory , Preanesthetic medication
 Sedative and hypnosis
mainly prolong stage 2 of NREMS, shorten
REMS and latency of sleep onset
Stages of Sleep
When subject falls asleep, EEG progresses
through stages:

non-rapid-eye movement sleep, NREMS
including 1、2、3、4 stages ，stage 3、4 also
called “ Slow wave sleep，SWS” （慢波睡眠）

rapid eye movement
sleep, REMS
SLEEP:
NREMS
REMS
NREMS
REMS：NS development，memory
NREMS： 1,2 stages
3,4 stages (Slow wave sleep，SWS)
growth ,restore
 Anticonvulsant and antiepileptic action
iv diazepam is the best choice for status
epilepticus (癫痫持续状态)
 Central muscle relaxing
treatment for central myotonia (肌强直)caused
by cerebral accident(脑血管意外) or spinal cord
injury(脊髓损伤)
Mechanism:
Promote GABA receptor function
γ- butylamino acid, GABA
 GABA A receptor consists of
twoα1,two β2 and one γ2
subunits.
 GABA A receptor, which
functions as a chloride ion
channel, is activated by the
inhibitory neurotransmitter
GABA .


GABA appears to interact
with αorβsubunits
triggering chloride
channel opening with
resultant membrane
hyperpolarization.

The binding site for BDZs
(BDZ-receptor) is located
between αandγsubunit.


BDZs appear to increase
the efficiency of
GABAergic synaptic
inhibition.
The enhancement in
chloride ion conductance
induced by the
interaction of BDZs with
GABA takes the form of
an increase in the
frequency of channelopening events.
Side effects:

common: hypersomnia, drowsiness, ataxia,
impaired judgment, diminished motor skills.

iv too fast
cause CNS depression

rarely fatal even following very high doses.
Except: the presence of other central
nervous system depressants; child, elder
patients；patients with severe liver disease
Treatment of toxicosis:
Ensuring the living symptom
Maintenance of plasma volume, renal output,
cardiac function
purging the stomach ；Hemodialysis
BDZ receptor antagonist
flumazenil (氟马西尼,安易行）

Tolerance and addiction

Fetal deformation
Barbiturates
Classification:
Drug
Phenobarbital
t ½( h)
onset
24-140
duration (h)
+
6-8
++
3-6
Secobarbital（司可巴比妥） 19-34
+++
2-3
Thiopental（硫喷妥 ）
++++
1-4
(luminal,苯巴比妥)
Amobarbital
8-42
(amytal,异戊巴比妥)
3-8
Action and use:
 sedative and hypnosis

shorten REMS

dose dependence
 anticonvulsant (phenobarbital)
 anesthesia and preanesthetic medication
(thiopental)
 enhance CNS depression
Mechanism

It can activate GABAA
receptor, potentiate
GABA action on
chloride entry into the
neuron.

Barbiturates: increase
the open time of Clchannel

BZ: increase the open
frequency of Cl- channel
Adverse effect
• drug hangover: tiredness after awakes
• tolerance: induce P-450 system
• addiction: abrupt withdrawal may cause
tremor, anxiety, weakness, restlessness,
nausea and vomiting
• respiratory depression
• allergy
Poisoning
Poisoning: overdoses can cause death,
depression of respiration and central
cardiovascular depression.
Treatment: artificial respiration;
purging the stomach of its contents;
alkalinization of blood and urine;
hemodialysis
BDZ’s ADVANTAGE:





therapeutic index high, safe range
broad
no inductive effects on P-450 system,
less tolerance
less effects on REMS, dependence,
withdraw syndrome slight
side effects mild
BZ receptor antagonist —— flumazenil
氟马西尼
Other sedatives
Chloral hydrate 水合氯醛
induces sleep in about 15 minutes and lasts
6~8 hours.
irritates to the gastrointestinal tract and causes
epigastric distress, also produces an unusual,
unpleasant taste sensation.
Central stimulants

Stimulating cerebral cortex:
Caffeine 咖啡因
Theophylline 茶碱

Stimulating medullary respiratory center
延髓呼吸中枢
Nikethamide 尼可刹米
Lobeline 洛贝林