S EDATIVE

H YPNOTICS
Dr Bushra Suhail

1
2
O BJECTIVES
 Define Sedative, Hypnotic & Anxiolytic •
Classify Sedative/Hypnotics
 Describe the mechanism of Action of
Benzodiazepines & Barbiturates
 Describe actions & adverse effects of
BZDs & Barbiturates
 Describe mechanism of action of
Buspiron&Zolpidem
 Describe differences between BZDs and
Buspiron
3 D EFINITION

 Hypnosis Induction of sleep

 Sedation Reduction of anxiety

 Anxiolytic A drug that reduces anxiety, a

sedative
4 BENZODIAZIPINES

Long-Acting Up to 100 hrs Flurazepam, Temazepam,

Diazepam, Clonazepam

Up to 40 hrs Lorazepam, Oxazepam,

Intermediate- Alprazolam,
Acting
Short-Acting Up to 6 hrs Midazolam, Triazolam

New Drugs BZ1 Zolpidem, Eszopiclone,

Slelective Zaleplon, Zopiclone
5 BARBITURATES

Long-Acting onset > Duratio Phenobarbitone,

1 Hr n < 12 Methyl-phenobarbitone,
Hr Barbitone, Metharbital

Intermediat onset 1 Duration Butabarbitone,

e-Acting Hr < 8 Hr Secobarbitone

Short-Acting onset 15 Duration Pentobarbitone,

Min < 6 Hr Cyclobarbitone

Ultra Short- onset 30 Duration Thiopentone,

Acting sec < 30 min Methohexital
6 OTHERS

Serotonin-Agonists 5 HT 1A Agonist 5 HT 1D Agonist

Buspiron,
Gepirone Sumatriptan

Melatonin Receptors Agonists. Ramelteon

Miscellaneous Chloral hydrate, Trichloroethanol,
Glutethamide, Meprobamate,
Antihistamines, Antipsychotic,
Antidepressants
7 ABSORBTION & DISTRIBUTION

 Lipophilic , so rapidly
absorbed
 Cross placental barrier
 Detectable in nursing milk
 Barbiturates enters brain (
Thiopental & redistributed
rapidly
8 EXCRETION

Urinary excretion
9 P HARMACODYNAMICS

 Mechanism of action
 Organ level effects
 Tolerance & Dependence
10 M ECHANISM OF ACTION OF BZ

 Receptors for BZ
are present in
thalamus, limbic
structures &
cerebral cortex

 Inc the
frequency of
GABA-mediated
chloride ion
channel opening
11
M ECHANISM OF ACTION
OF BARBITURATES

 Receptors are present

in midbrain reticular
formation facilitating
and prolonging the
inhibitory effects of
GABA and glycine.

the duration of
 Inc
GABA-mediated
chloride ion channel
opening

 Alsoblock excitatory
glutamic acid and
sodium channels
12 O RGAN LEVEL EFFECTS

A. SEDATION
B. HYPNOSIS
C. ANESTHESIA
D. ANTICONVULSANT
E. MUSCLE RELAXATION
F. EFFECT ON CVS & RESPIRATION
13 A. SEDATION

 AllBZ causes
sedation

 Anterograde
amnesia

 Disinhibition of
PUNISHMENT
SUPPRESSED
BEHAVOIUR in
animals
14 B. HYPNOSIS

 Promote sleep
onset and inc the
duration of the
sleep state.
 REM sleep
duration is
usually dec at
high doses.
15 C. ANESTHESIA

 Athigh doses
loss of
consciousness
may occur, with
amnesia and
suppression of
reflexes.
 Anterograde
amnesia is with
benzodiazepines
16

Anesthesia can be produced

by
most barbiturates (eg,
thiopental) and
certain benzodiazepines
(eg, midazolam).
17 D. ANTICONVULSANT

 Suppression of seizure
activity occurs with high
doses of most barbiturates
and some of the BZ.

 Selective anticonvulsant
action occurs with only a
few of these drugs
(phenobarbital,
clonazepam).

 High doses of intravenous

diaze , lorazepam, or
phenobarbital are used in
status epilepticus
18 E. MUSCLE RELAXATION

 Occurs in high
doses
 Diazepam is
effective at
sedative dose
levels for specific
spasticity states,
including cerebral
palsy.
 Meprobamate is
also a muscle
relaxant.
19 F. EFFECT ON CVS & RESP

 High doses especially alcohols

and barbiturates, can cause
depression of medullary
neurons, leading to respiratory
arrest, hypotension, and
cardiovascular collapse.
 These effects are the cause of
death in suicidal overdose.
20
21 T OLERANCE & D EPENDENCE

 Tolerance occurs
in chronic or in
high dosage.
 Cross-tolerance
may occur
among different
chemical
subgroups.
22

 Psychological &
physiologic
dependence occurs
frequently with most
sedative-hypnotics.
 Abstinence syndrome
(withdrawal state)
when the drug is
discontinued
23 CLINICAL USES

1. ANXIETY STATES

2. SLEEP DISORDERS
more recently there has been increasing use of
zolpidem, zaleplon, and eszopiclone in insomnia,
since they have rapid onset with minimal effects
on sleep patterns and cause less daytime
cognitive impairment than benzodiazepines.

3. ANESTHESIA
24 S PECIAL USES

 include the management of seizure disorders

(eg, clonazepam, phenobarbital) and bipolar
disorder (eg, clonaz-epam)

 treatment of muscle spasticity (eg,

diazepam).

 Longer acting benzodiazepines (eg,

chlordiazepoxide, diazepam) are used in the
management of withdrawal states in persons
physiologically dependent on ethanol and
other sedative-hypnotics
25 TOXICITY

 Psychomotor dysfunction
 CNS depression
 Overdosage
26 1. P SYCHOMOTOR DYSFUNCTION

 Day time sedation

 Falls and fractures in elderly
 cognitive impairment,
decreased psychomotor
 skills,
 Date rape
 Sleep driving
27 2. CNS DEPRESSION

Occurs with
alcoholic
beverages,
antihistamine
s,
antipsychotic
drugs, opioid
analgesics,
and TCA.
28 4. OTHERS

 Acute intermittent porphyria

with barbiturates
 Displacement of coumarins
leading to inc anticoagulant
effect.
 Barbiturates induce liver
metabolizing enzymes .
29
NEWER
BENZODIAPINES

Zolpidem,

Eszopiclone,

Zaleplon,

Zopiclone
30 MOA

 are not benzodiazepines but appear to

exert their CNS effects via interaction
with certain benzodiazepine receptors,
classified as BZ1or ω1.
 In contrast to benzodiazepines, these
drugs bind more selectively only with
GABA receptor isoforms that contain
α1subunits.
31

 Their CNS depressant effects can be antago-

nized by

 flumazenil
 Used in sleep disorders when sleep onset is
delayed

 However, unlike benzodiazepines, these drugs

are not used in seizures or in muscle spasticity
states.
32
A DVERSE EFFECTS

 Additive CNS depression with

ethanol and other depressants
Short half-lives
 Extension of CNS depressant
effects; dependence liability but
less than others BZ.
33 BUSPIRONE

 Buspirone is a selective anxiolytic, with

minimal CNS depressant effects (it does not
affect driving skills)

 has no anticonvulsant or muscle relaxant

properties.

 The drug interacts with the 5-HT1A

subclass of brain serotonin receptors as a
partial agonist, but the precise mechanism of
its anxiolytic effect is unknown.
34
BUSPIRONE
 Buspirone has a slow onset of
action (>1 week) and is used in
generalized anxiety disorders,
 is less effective in panic disorders.
Toler-ance development is minimal
 little rebound anxiety or withdrawal
symptoms on discontinuance.
 A/E. GI distress, tachycardia;
paresthesias, pupillary
constriction
35
RAMELTEON

 Activates MT1 and MT2

receptors in
suprachiasmatic nucleus
 Used in Sleep disorders, esp
when sleep onset is delayed
Not a controlled substance
36 A DVERSE EFFECTS

 Dizziness, fatigue,
 endocrine changes
 including decreased tes-
tosterone and increased
prolactin.
37 S UVOREXANT

 Suvorexant
 a recently approved antagonist at orexin
receptors, has hypnotic properties
38

 A young girl took overdose of diazepam

incidentally what antidote would be
effective?
 Flumazenil
 to reverse the symptoms of CNS
depression
39