Chapter 14

Sedative-Hypnotic drugs
 [Definitions]
Sedative-Hypnotics: Assignment of a
drug to the sedative-hypnotic class indicates
that its major therapeutic use is to cause
sedation (with concomitant relief of anxiety) or
to encourage sleep.
 [Definations]

Sedation:An effective sedative agent should

reduce anxiety and exert an effect with little
or no effect on motor or mental functions.
 [Definitions]
• 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.

• can be achieved with most sedative drugs

simply by increasing the dose.
Figure 14-1 Dose-response curves for two
hypothetical sedative-hypnotics
 [Classification]
• 1. Benzodiezepines

• 2. Barbiturates

• 3.Other agents:e.g.chloral hydrate

 Section 1
Benzodiazepines
• The most widely used Sedative-
Hypnotics.
• They are more effective and safer
than barbiturates.
 [Classification]
• Short-acting: The half-life is 2-4 hours,
e.g. Triazolam.
• Intermediate-acting: The half-life is 5-10
hours, e.g. Chlordiazepoxide
• Long-acting: The half-life is 30-60 hours,
e.g. diazepam and flurazepam.
 [Pharmacokinetics]
★ Absorption and distribution
1. oral
absorption are well , im. absorption are slow
and unreliable; iv. absorption are rapidly

2. are highly lipid-soluble and are largely binding

to plasma proteins

3. Removal from the brain to the other tissues

throughout the body
 [Pharmacokinetics]
Biotransformation
1. metabolized by the liver to
compounds that are also active.

2. metabolites are excreted in the

urine.
 [effects and uses]
1.Anti-anxiety
◆ at the lowest effective doses

◆ used for the relieving of anxiety states,

including restlessness,worry,stress and
phobia states .Chlordiazepoxide and
diazepam are often used.
 2. Sedation
◆exert calming effects at relatively low
doses.
used to relieve the stress of patients.
◆Diazepam can cause temporary loss of
memory after iv.
used for patients undergoing tracheoscopy
and electric defibrillation before the
treatment or examination.
 3. Hypnosis

rapid eye movement sleep

natural sleep
  non-rapid eye movement sleep
(includes slow-wave sleep)
•
 3. Hypnosis
Advantages:
• The latency of sleep onset is decreased
(time to fall asleep);
• The duration of stage 2 NREM sleep is
increased;
• The duration of REM sleep is decreased;

• The duration of stage 4 NREM slow-

wave sleep is decreased.
 Disadvantages
• A similar pattern of “REM rebound” can
be detected following abrupt cessation of
drug treatment with sedative-hypnotics,
especially when drugs with short
durations of action are used at high
doses.
• The use of sedative-hypnotics for more
than 1–2 weeks leads to some tolerance to
their effects on sleep patterns.
 Effects and Uses
4.Anticonvulsant effects
 Inhibit the development and spread of
epileptiform activity in the CNS and are useful
in the treatment of convulsion and status
epileptics.
Clonazepam is useful in the chronic treatment
of epilepsy, diazepam is the drug of first choice
in terminating grand mal epileptic seizures and
status epileptics.
 Effects and Uses
5.Relaxation of muscle
inhibit polysynaptic reflexes and internuncial
transmission (in CNS), and depress transmission
at the skeletal neuromuscular junction, lead to
muscle relaxation.
◆Useful in the treatment of skeletal muscle spasms,
multiple sclerosis and cerebral palsy.
 [Mechanism of action]

GABA is the major inhibitory neurotransmitter in

the central nervous system.
GABAA receptor, which functions as a chloride ion
channel, is activated by the inhibitory
neurotransmitter GABA .
 Binding of GABA to its receptors may open
chloride channels and facilitate Cl- entry into
neurons. The influx of Cl- cause a small
hyperpolarization that moves the postsynaptic
potential and thus inhibits the formation of
action potentials, which produces an inhibitory
effect on neuronal conduction.
 Benzodiazepines bind to the GABAA receptor
present in the CNS ， which promotes GABA
binding to it’s receptors , thus may increase the
frequency of Cl- channel-opening and facilitate
more Cl- entry into neurons that increase the
efficiency of GABA synaptic inhibition.
 Adverse reactions

1.CNS depression

dizziness, asthenia, drowsiness etc.

2.Tolerance and Dependence.
 Section 2

Barbiturates
 [Classification]
1.Ultra-short-acting:
Duration of action is about 30’, e.g. thiopental.

2.Short-acting:
2-3 hours, e.g. secobarbital.

3.Intermediate-acting:
3-6 hours,e.g. pentobarbital.

4.Long-acting:
6-8 hours, e.g. Phenobarbital.
 Pharmacokinetics
 Oral administration are absorbed rapidly.
Duration of action depends on metabolic
degradation, degree of lipid solubility and
extent of binding to serum proteins. Lipid
solubility plays a major role.
 Pharmacokinetics
Enzyme induction:induce hepatic microsomal
drug-metabolizing enzymes, especially
phenobarbital.
(1) leads to tolerance.
(2) Diminishes the action of many drugs (e.g
phenytoin)
 Pharmacokinetics

excreted via kidney.

Alkalinization of urine promotes

excretion of babiturates.
 Mechanisms
1.↑GABA inhibition(duration of Cl-
channel opening↑)
2.interfere with sodium and potassium
transport that leads to inhibition of the
mesencephalic reticular activating system.
 [effects and uses]
1. Sedation and hypnosis
The duration of sleep is increased and the
time of inducing sleep is decreased.
2.Antiepileptism
Phenobarbital is often used for epileptism
in infant and children as a first choice drug.
3. Anesthesia
Thiopental is used intravenously to
induce anesthesia.
 [effects and uses]
• 4.decrease oxygen utilization by brain
• especially in anesthetic doses, significantly
decrease oxygen utilization by brain, which
may be of value in lessening cerebral edema
caused by surgery or trauma and in
protecting against cerebral infarction
duration cerebral ischemia.
 Adverse reactions
1. CNS depressant effects
dizziness for hours after waking, sedation and a
decrease in REMS .

2. Dependence
Physiology dependence

Psychological dependence
 Adverse reactions
 3.Poisoning

An overdose can result in coma,severe

respiratory depression.

Alkalization of the urine often aids in the

elimination of phenobarbital.
 Chloral hydrate
 a relatively safe hypnotic drug
 used mainly in children and the elderly
 usually administered by enema in children

Paraldehyde
It is used for patients with hepatic or
renal failure because it is mainly
eliminated via the lungs.