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
