Sedative-Hypnotic Drugs
[Definations]
1.Sedation:An effective sedative agent should reduce anxiety and exert a effect
with little or no effect on motor or mental functions.
2.Hypnosis:A hypnotic drug should produce drowsiness and encourage the onset
and maintenance of a state of sleep that as far as possible resembles the natural sleep
state.Hypnotic effects can be achieved with most sedative drugs simply by increasing
the dose.
[Classification]
1.Barbiturates.
2.Benzodiezepines.
3.Other agents:e.g.chloral hydrate.
[Specificity]1.Graded dose-dependent depression of CNS function2.Tolerance
3.Dependence:Psychologic
Physiologic
Setion 1 Benzodiezepines
The most widely used Sedative-Hypnotics.
Have largely replaced barbiturates in the treatment of anxiety,since the
benzodiezepines are more effective and safer.
[Pharmocokinetics]
1.Absorption and distribution A:lipophilic
B:rapidly and completely absorbed after oral administration
C:distributed throughout the body
2.Fate
A.metabolized by the liver
B.excreted by kidey.
[Mechanism of action]
Increase the efficiency of γ-aminobutyric acid (GABAergic) inhibition•enhance
R affinity for GABA
• increase the frequency of CL channel
opening
•do not substitute for GABA
[Pharmacologic effects and therapeutic uses]
All of the drugs exhibit the following actions to a greater or lesser extent:
1.Antianxiety
Benzodiezepines are used for relieving of anxiety states,including
restlessness,worry,stress that accompanies some forms of depression and
schizophrenia. They are thought to reduce anxiety by selectively inhibiting neuronal
circuits in the limbic system of the brain.
2.Sedation
They are used prior to general anesthesis to relieve the stress of
patients.Diazepam can cause temporary loss of memory after iv.It is used for patients
undergoing tracheoscopy and electric defibrillation before the treatment or
examination.
3.Hypnosis
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rapid eye movement sleep(REM)
natural sleep
Non-rapid eye movement sleep(NREM) includes slow-wave
sleep(SRM)Significantly reduces both sleep-induction time and the
number of awakenings,and increases the duration of sleep.
advantages: (comparied with barbiturates):
(1).higher TI
(2)↓the duration of slow-wave sleep
little influences on REM
So the rebound insomnia upon discontinuance of drugs is lighter
(3)do not induce hepatic enzyme
(4)dependence is light4.Anticonvulsant effects
useful in the treatment of convulsion and status epilepticus.
5.Musle relaxant
Relax the spasticity of skeletal mucle.Diazepam is useful in the treatment of
multiple sclerosis and cerebral palsy.
[Adverse effects]
have a low toxicity and wide margin of safety.
1.CNS depression
dizziness,asthenia,drowsiness etc.
2.Tolerance,dependence and addiction
Section 2 Babiturates
[Classification]
Babiturates are classified into four kinds on the basis of onset of action and
duration of action.
1.Ultra-short-acting:
Duration of action is about 30 min,e.g.thiopental.
2.Short-acting:
Duration of action is 2-3 hours,e.g.secobarbital.
3.Intermediate-acting:
Duration of action is 3-6 hours,e.g. pentobarbital.
4.Duration of action is 6-8 hours,e.g.phenobarbital.
[Pharmacokinetics]
1.Duration of action of babiturates depends on degree of lipid
solubility.Ultra-short-acting drugs are highly lipid-soluble,whereas long-acting drugs
are lowly lipid-soluble.
2.Enzyme induction:induce P-450 (microsomal drug-metabolizing enzymes in
the liver) Most babiturates,especially phenobarbital.
(1)The action of the enzymes results in increased the degration of
babiturates,ultimately leading to tolerance.
(2)Diminishes the action of many drugs that are dependent on P-450 metabolism
to reduce their concentration(e.g.anticoagulants,phenytoin)
3.excreted via kidney.Alkalinization of urine promotes excretion of babiturates.
2
[Mechanism of action]
1.↑GABAergic inhibition(duration of Cl- channel opening↑)
2.GABAmimetic(high dose)
[Effects and uses]
1.Anesthesia
Thiopental is used intravenously to induce anesthesia.
2.Antiepilepsy
Phenobarbital is often used for epileptism in infant and children.
[Adverse effects]
1.After effect
Leads to nausea and dizziness for hours after waking.
2.Dependence
Physiology and psychologocal dependence can occur.Abrupt withdrawal may
cause tremors,weakness,nausea and vomiting.
3.Poisoning
An overdose can result in coma,severe respiratory depression.Treatment of acute
overdosage includes supporting respiration and circulation,purging the stomach of its
contents of the drug has recently taken.Alkalization of the urine often aids in the
elimination of phenobarbital.
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