Anxiolytic Sedative and Hypnotic Drugs lecture pdf - د. نجلاء

Anxiolytic

Anxiolytic ,,

Sedative

and

Hypnotic

Drugs

Drugs--2

Anxiolytic

Anxiolytic ,,

Sedative

and

Hypnotic

Drugs

Drugs--2



Benzodiazepines are the most widely

Benzodiazepines are the most widely
used

used anxiolytic

anxiolytic drugs.

drugs. They have largely

They have largely

replaced barbiturates because:



The

The benzodiazepines are safer(have a

benzodiazepines are safer(have a

wide

wide therapeutic index)

therapeutic index) and more

and more

effective



Not

Not cause drug

cause drug –

– drug

drug interaction(not

interaction(not

induce hepatic

induce hepatic microsomal

microsomal enzyme)

enzyme)



Produce

Produce tolerance and psychological

tolerance and psychological

dependence but physical dependence

dependence but physical dependence
and withdrawal symptom are less

and withdrawal symptom are less marked

marked



Benzodiazepines are the most widely

Benzodiazepines are the most widely
used

used anxiolytic

anxiolytic drugs.

drugs. They have largely

They have largely

replaced barbiturates because:



The

The benzodiazepines are safer(have a

benzodiazepines are safer(have a

wide

wide therapeutic index)

therapeutic index) and more

and more

effective



Not

Not cause drug

cause drug –

– drug

drug interaction(not

interaction(not

induce hepatic

induce hepatic microsomal

microsomal enzyme)

enzyme)



Produce

Produce tolerance and psychological

tolerance and psychological

dependence but physical dependence

dependence but physical dependence
and withdrawal symptom are less

and withdrawal symptom are less marked

marked

Benzodiazepines

Benzodiazepines are classified according to

are classified according to

their duration of action into:



Short

Short –

– acting

acting :: Oxazepam

Oxazepam,, Triazolam

Triazolam ((3

3--8

8))

hours



Intermediate

Intermediate –

– acting

acting :: Alprazolam

Alprazolam,,

Lorazepam

Lorazepam,, Temazepam

Temazepam ((10

10--20

20)) hours

hours



Long

Long--acting

acting :: Chlordiazepoxide

Chlordiazepoxide, Diazepam,

, Diazepam,

Flurazepam

Flurazepam,,

Benzodiazepines

Benzodiazepines are classified according to

are classified according to

their duration of action into:



Short

Short –

– acting

acting :: Oxazepam

Oxazepam,, Triazolam

Triazolam ((3

3--8

8))

hours



Intermediate

Intermediate –

– acting

acting :: Alprazolam

Alprazolam,,

Lorazepam

Lorazepam,, Temazepam

Temazepam ((10

10--20

20)) hours

hours



Long

Long--acting

acting :: Chlordiazepoxide

Chlordiazepoxide, Diazepam,

, Diazepam,

Flurazepam

Flurazepam,,



Benzodiazepines



ANXIOLYTIC

ANXIOLYTIC:: Alprazolam

Alprazolam,,

chlordiazepoxide

chlordiazepoxide,, diazepam,

diazepam,

lorazepam



HYPNOTIC:

HYPNOTIC: Triazolam

Triazolam,, temazepam

temazepam,,

flurazepam

flurazepam..



Benzodiazepines



ANXIOLYTIC

ANXIOLYTIC:: Alprazolam

Alprazolam,,

chlordiazepoxide

chlordiazepoxide,, diazepam,

diazepam,

lorazepam



HYPNOTIC:

HYPNOTIC: Triazolam

Triazolam,, temazepam

temazepam,,

flurazepam

flurazepam..

Mechanism of action:



Binding of GABA (the major inhibitory

Binding of GABA (the major inhibitory
neurotransmitter in the central nervous

neurotransmitter in the central nervous
system

system)) to its receptor

to its receptor triggers

triggers an opening of

an opening of

a chloride channel

a chloride channel,, which leads to an

which leads to an

increase in chloride conductance



Benzodiazepines

Benzodiazepines increase the frequency

increase the frequency of

channel openings produced by GABA. The

channel openings produced by GABA. The
influx of chloride ions causes

influx of chloride ions causes
hyperpolarization

hyperpolarization of the cell making it more

of the cell making it more

difficult to depolarize and there for reduces

difficult to depolarize and there for reduces
neural excitability

neural excitability

Mechanism of action:



Binding of GABA (the major inhibitory

Binding of GABA (the major inhibitory
neurotransmitter in the central nervous

neurotransmitter in the central nervous
system

system)) to its receptor

to its receptor triggers

triggers an opening of

an opening of

a chloride channel

a chloride channel,, which leads to an

which leads to an

increase in chloride conductance



Benzodiazepines

Benzodiazepines increase the frequency

increase the frequency of

channel openings produced by GABA. The

channel openings produced by GABA. The
influx of chloride ions causes

influx of chloride ions causes
hyperpolarization

hyperpolarization of the cell making it more

of the cell making it more

difficult to depolarize and there for reduces

difficult to depolarize and there for reduces
neural excitability

neural excitability

Actions

Actions::


 The benzodiazepines have

The benzodiazepines have neither

neither

antipsychotic activity nor analgesic

antipsychotic activity nor analgesic action

action



 Reduction of anxiety:

Reduction of anxiety: At low doses, the

At low doses, the

benzodiazepines are

benzodiazepines are anxiolytic

anxiolytic



 Sedative and hypnotic actions:

Sedative and hypnotic actions: All of

All of

the benzodiazepines used to treat

the benzodiazepines used to treat
anxiety have some sedative properties,

anxiety have some sedative properties,
and some can produce hypnosis

and some can produce hypnosis
(artificially produced sleep) at higher

(artificially produced sleep) at higher
doses.

doses.



 Anticonvulsant:

Anticonvulsant: some are used to treat

some are used to treat

epilepsy (status

epilepsy (status epilepticus

epilepticus)) and other

and other

seizure disorders.



 Muscle relaxant:

Muscle relaxant: At high doses, the

At high doses, the

benzodiazepines relax the spasticity of

benzodiazepines relax the spasticity of
skeletal muscle

skeletal muscle



 Sedative and hypnotic actions:

Sedative and hypnotic actions: All of

All of

the benzodiazepines used to treat

the benzodiazepines used to treat
anxiety have some sedative properties,

anxiety have some sedative properties,
and some can produce hypnosis

and some can produce hypnosis
(artificially produced sleep) at higher

(artificially produced sleep) at higher
doses.

doses.



 Anticonvulsant:

Anticonvulsant: some are used to treat

some are used to treat

epilepsy (status

epilepsy (status epilepticus

epilepticus)) and other

and other

seizure disorders.



 Muscle relaxant:

Muscle relaxant: At high doses, the

At high doses, the

benzodiazepines relax the spasticity of

benzodiazepines relax the spasticity of
skeletal muscle

skeletal muscle

Therapeutic

Therapeutic uses

uses::



 Anxiety

Anxiety disorders: Benzodiazepines are

disorders: Benzodiazepines are

effective for the treatment of the

effective for the treatment of the anxiety.

anxiety.

generalized

generalized anxiety disorder,

anxiety disorder, specific phobias,

specific phobias,

such as fear of flying.



 Muscular disorders:

Muscular disorders: Diazepam is useful in the

Diazepam is useful in the

treatment of skeletal muscle spasms,

treatment of skeletal muscle spasms, multiple

multiple

sclerosis and cerebral palsy

Therapeutic

Therapeutic uses

uses::



 Anxiety

Anxiety disorders: Benzodiazepines are

disorders: Benzodiazepines are

effective for the treatment of the

effective for the treatment of the anxiety.

anxiety.

generalized

generalized anxiety disorder,

anxiety disorder, specific phobias,

specific phobias,

such as fear of flying.



 Muscular disorders:

Muscular disorders: Diazepam is useful in the

Diazepam is useful in the

treatment of skeletal muscle spasms,

treatment of skeletal muscle spasms, multiple

multiple

sclerosis and cerebral palsy



 The

The shorter

shorter--acting agents are

acting agents are used as

used as

premedication for anxiety

premedication for anxiety--provoking and

provoking and

unpleasant procedures, such as endoscopic,

unpleasant procedures, such as endoscopic,
bronchoscopic

bronchoscopic,, dental procedures.

dental procedures. They

They

cause

cause a form of conscious sedation, allowing

a form of conscious sedation, allowing

the person to

the person to be receptive to instructions

be receptive to instructions

during these procedures

during these procedures..



 Midazolam

Midazolam is an

is an injectable

injectable--only

only

benzodiazepine also used for the induction

benzodiazepine also used for the induction
of anesthesia

of anesthesia



 The

The shorter

shorter--acting agents are

acting agents are used as

used as

premedication for anxiety

premedication for anxiety--provoking and

provoking and

unpleasant procedures, such as endoscopic,

unpleasant procedures, such as endoscopic,
bronchoscopic

bronchoscopic,, dental procedures.

dental procedures. They

They

cause

cause a form of conscious sedation, allowing

a form of conscious sedation, allowing

the person to

the person to be receptive to instructions

be receptive to instructions

during these procedures

during these procedures..



 Midazolam

Midazolam is an

is an injectable

injectable--only

only

benzodiazepine also used for the induction

benzodiazepine also used for the induction
of anesthesia

of anesthesia



 Seizures:

Seizures:

Clonazepam

Clonazepam is occasionally used in the treatment

is occasionally used in the treatment

of certain types of

of certain types of epilepsy

epilepsy

Diazepam

Diazepam and

and lorazepam

lorazepam are the drugs of choice

are the drugs of choice

in terminating grand mal epileptic seizures and

in terminating grand mal epileptic seizures and
status

status epilepticus

epilepticus..

chlordiazepoxide

chlordiazepoxide,,

,, diazepam, and

diazepam, and oxazepam

oxazepam are

are

useful in the acute treatment of alcohol

useful in the acute treatment of alcohol
withdrawal

withdrawal



 Seizures:

Seizures:

Clonazepam

Clonazepam is occasionally used in the treatment

is occasionally used in the treatment

of certain types of

of certain types of epilepsy

epilepsy

Diazepam

Diazepam and

and lorazepam

lorazepam are the drugs of choice

are the drugs of choice

in terminating grand mal epileptic seizures and

in terminating grand mal epileptic seizures and
status

status epilepticus

epilepticus..

chlordiazepoxide

chlordiazepoxide,,

,, diazepam, and

diazepam, and oxazepam

oxazepam are

are

useful in the acute treatment of alcohol

useful in the acute treatment of alcohol
withdrawal

withdrawal



 Sleep

Sleep disorded

disorded ::Flurazepam

Flurazepam has a long

has a long--acting

acting

effect and causes

effect and causes no

no rebound insomnia.

rebound insomnia.



 Temazepam

Temazepam:: This drug is useful in patients who

This drug is useful in patients who

experience frequent wakening.

experience frequent wakening. the

the peak sedative

peak sedative

effect occurs

effect occurs 1

1 to

to 3

3 hours after an oral dose;

hours after an oral dose; and

and

should

should be given

be given 1

1 to

to 2

2 hours before

hours before bedtime

bedtime..



 Triazolam

Triazolam:: short duration of action and, therefore,

short duration of action and, therefore,

is used to induce sleep in patients with recurring

is used to induce sleep in patients with recurring
insomnia. Whereas

insomnia. Whereas temazepam

temazepam is useful for

is useful for

insomnia caused by the inability to stay asleep,

insomnia caused by the inability to stay asleep,
triazolam

triazolam is effective in treating individuals who

is effective in treating individuals who

have difficulty in going to

sleep



 Sleep

Sleep disorded

disorded ::Flurazepam

Flurazepam has a long

has a long--acting

acting

effect and causes

effect and causes no

no rebound insomnia.

rebound insomnia.



 Temazepam

Temazepam:: This drug is useful in patients who

This drug is useful in patients who

experience frequent wakening.

experience frequent wakening. the

the peak sedative

peak sedative

effect occurs

effect occurs 1

1 to

to 3

3 hours after an oral dose;

hours after an oral dose; and

and

should

should be given

be given 1

1 to

to 2

2 hours before

hours before bedtime

bedtime..



 Triazolam

Triazolam:: short duration of action and, therefore,

short duration of action and, therefore,

is used to induce sleep in patients with recurring

is used to induce sleep in patients with recurring
insomnia. Whereas

insomnia. Whereas temazepam

temazepam is useful for

is useful for

insomnia caused by the inability to stay asleep,

insomnia caused by the inability to stay asleep,
triazolam

triazolam is effective in treating individuals who

is effective in treating individuals who

have difficulty in going to

sleep

Pharmacokinetics

•• lipophilic

lipophilic,,

•• rapidly and completely absorbed after oral

rapidly and completely absorbed after oral

administration

•• distribute throughout the body .

distribute throughout the body .



 The

The half

half--lives of the benzodiazepines are very

lives of the benzodiazepines are very

important clinically, because the duration of

important clinically, because the duration of
action may determine the therapeutic

action may determine the therapeutic
usefulness,

usefulness, The longer

The longer--acting agents form

acting agents form

active metabolites with long half

active metabolites with long half--lives.

lives.

However, with some benzodiazepines, the

However, with some benzodiazepines, the
clinical durations of action do not always

clinical durations of action do not always
correlate with actual

correlate with actual half

half--lives.

lives.

Pharmacokinetics

•• lipophilic

lipophilic,,

•• rapidly and completely absorbed after oral

rapidly and completely absorbed after oral

administration

•• distribute throughout the body .

distribute throughout the body .



 The

The half

half--lives of the benzodiazepines are very

lives of the benzodiazepines are very

important clinically, because the duration of

important clinically, because the duration of
action may determine the therapeutic

action may determine the therapeutic
usefulness,

usefulness, The longer

The longer--acting agents form

acting agents form

active metabolites with long half

active metabolites with long half--lives.

lives.

However, with some benzodiazepines, the

However, with some benzodiazepines, the
clinical durations of action do not always

clinical durations of action do not always
correlate with actual

correlate with actual half

half--lives.

lives.



 Most benzodiazepines, including

Most benzodiazepines, including
chlordiazepoxide

chlordiazepoxide and diazepam, are

and diazepam, are

metabolized by the hepatic

metabolized by the hepatic microsomal

microsomal

system to compounds that are also

system to compounds that are also
active.

active.



 The

The benzodiazepines are excreted in

benzodiazepines are excreted in

the urine as

the urine as glucuronides

glucuronides or oxidized

or oxidized

metabolites

metabolites..



 Most benzodiazepines, including

Most benzodiazepines, including
chlordiazepoxide

chlordiazepoxide and diazepam, are

and diazepam, are

metabolized by the hepatic

metabolized by the hepatic microsomal

microsomal

system to compounds that are also

system to compounds that are also
active.

active.



 The

The benzodiazepines are excreted in

benzodiazepines are excreted in

the urine as

the urine as glucuronides

glucuronides or oxidized

or oxidized

metabolites

metabolites..



 All the benzodiazepines cross the

All the benzodiazepines cross the
placental barrier and may depress the

placental barrier and may depress the
CNS of the newborn if given before

CNS of the newborn if given before
birth.

birth.



 Nursing infants may also become

Nursing infants may also become
exposed to the drugs in breast milk

exposed to the drugs in breast milk

Adverse effects



 Drowsiness

Drowsiness and confusion

and confusion::



 Psychological

Psychological and physical dependence on

and physical dependence on

benzodiazepines can develop if high doses of the

benzodiazepines can develop if high doses of the
drugs are given over a prolonged

drugs are given over a prolonged period

period



 withdrawal

withdrawal symptoms, including confusion, anxiety

symptoms, including confusion, anxiety,,

insomnia

insomnia,, tension,

tension, and rarely, seizures.

and rarely, seizures.

••

a short

a short elimination

elimination half

half--life(rapidly

life(rapidly eleminated

eleminated),

), such

such

as triazolam

triazolam,, induce more abrupt

induce more abrupt severe

severe withdrawal

withdrawal

reactions than

reactions than drugs

drugs that are slowly eliminated, such

that are slowly eliminated, such

as flurazepam

flurazepam

Adverse effects



 Drowsiness

Drowsiness and confusion

and confusion::



 Psychological

Psychological and physical dependence on

and physical dependence on

benzodiazepines can develop if high doses of the

benzodiazepines can develop if high doses of the
drugs are given over a prolonged

drugs are given over a prolonged period

period



 withdrawal

withdrawal symptoms, including confusion, anxiety

symptoms, including confusion, anxiety,,

insomnia

insomnia,, tension,

tension, and rarely, seizures.

and rarely, seizures.

••

a short

a short elimination

elimination half

half--life(rapidly

life(rapidly eleminated

eleminated),

), such

such

as triazolam

triazolam,, induce more abrupt

induce more abrupt severe

severe withdrawal

withdrawal

reactions than

reactions than drugs

drugs that are slowly eliminated, such

that are slowly eliminated, such

as flurazepam

flurazepam

Precautions:

Precautions:


 In

In treating patients with liver disease.

treating patients with liver disease.



 In

In patients with acute narrow

patients with acute narrow--angle glaucoma.

angle glaucoma.



 Alcohol and other CNS depressants enhance

Alcohol and other CNS depressants enhance
the sedative

the sedative--hypnotic effects of the

hypnotic effects of the

benzodiazepines.

Precautions:

Precautions:


 In

In treating patients with liver disease.

treating patients with liver disease.



 In

In patients with acute narrow

patients with acute narrow--angle glaucoma.

angle glaucoma.



 Alcohol and other CNS depressants enhance

Alcohol and other CNS depressants enhance
the sedative

the sedative--hypnotic effects of the

hypnotic effects of the

benzodiazepines.

Benzodiazepine Antagonist

Benzodiazepine Antagonist


 Flumazenil

Flumazenil (is a GABA

(is a GABA--receptor antagonist)

receptor antagonist)

that can rapidly reverse the effects of

that can rapidly reverse the effects of
benzodiazepines(competitively occupies a

benzodiazepines(competitively occupies a
GABA

GABA--receptor without

receptor without causing a functional

causing a functional

change in CL channel) .

•• for

for intravenous administration only

intravenous administration only..

•• rapid Onset of action

rapid Onset of action

•• short duration,

short duration, with a half

with a half--life of about

life of about 1

hour.

Frequent

Frequent administration may be necessary to

administration may be necessary to

maintain reversal of a long

maintain reversal of a long--acting

acting

benzodiazepine

Benzodiazepine Antagonist

Benzodiazepine Antagonist


 Flumazenil

Flumazenil (is a GABA

(is a GABA--receptor antagonist)

receptor antagonist)

that can rapidly reverse the effects of

that can rapidly reverse the effects of
benzodiazepines(competitively occupies a

benzodiazepines(competitively occupies a
GABA

GABA--receptor without

receptor without causing a functional

causing a functional

change in CL channel) .

•• for

for intravenous administration only

intravenous administration only..

•• rapid Onset of action

rapid Onset of action

•• short duration,

short duration, with a half

with a half--life of about

life of about 1

hour.

Frequent

Frequent administration may be necessary to

administration may be necessary to

maintain reversal of a long

maintain reversal of a long--acting

acting

benzodiazepine

Side

Side effects:

effects:

1.Dizziness, nausea, vomiting, and

.Dizziness, nausea, vomiting, and agitation

agitation

2.withdrawal

.withdrawal in dependent patients

in dependent patients

3.. seizures

seizures

•• If

If a benzodiazepine is used to control

a benzodiazepine is used to control

seizure activity

•• If

If the patient ingests

the patient ingests tricyclic

tricyclic antidepressants

antidepressants

Side

Side effects:

effects:

1.Dizziness, nausea, vomiting, and

.Dizziness, nausea, vomiting, and agitation

agitation

2.withdrawal

.withdrawal in dependent patients

in dependent patients

3.. seizures

seizures

•• If

If a benzodiazepine is used to control

a benzodiazepine is used to control

seizure activity

•• If

If the patient ingests

the patient ingests tricyclic

tricyclic antidepressants

antidepressants

••

Other

Other anxiolytic

anxiolytic drugs:

drugs: buspirone

buspirone,,

hydroxyzine

Buspirone

••

Is useful in the treatment of generalized anxiety disorder

••

has efficacy comparable to that of the benzodiazepines.

••

Mode of action differs from that of the benzodiazepines

Mode of action differs from that of the benzodiazepines
because:

because:

••

The actions of

The actions of buspirone

buspirone appear to be mediated by

appear to be mediated by

Buspirone

••

Is useful in the treatment of generalized anxiety disorder

••

has efficacy comparable to that of the benzodiazepines.

••

Mode of action differs from that of the benzodiazepines

Mode of action differs from that of the benzodiazepines
because:

because:

••

The actions of

The actions of buspirone

buspirone appear to be mediated by

appear to be mediated by

•• Serotonin (

Serotonin (5

5--HT

) receptors,

) receptors, buspirone

buspirone

displays some affinity for DA

dopamine

receptors and

receptors and 5

5--HT

serotonin receptors

•• undergoes metabolism by CYP

undergoes metabolism by CYP3

4; thus, its

; thus, its

half

half--life is shortened if taken with

life is shortened if taken with rifampin

rifampin(an

(an

inducer of the enzyme)

•• lengthened if taken with erythromycin(an

lengthened if taken with erythromycin(an
inhibitor of the enzyme)

inhibitor of the enzyme)

•• Serotonin (

Serotonin (5

5--HT

) receptors,

) receptors, buspirone

buspirone

displays some affinity for DA

dopamine

receptors and

receptors and 5

5--HT

serotonin receptors

•• undergoes metabolism by CYP

undergoes metabolism by CYP3

4; thus, its

; thus, its

half

half--life is shortened if taken with

life is shortened if taken with rifampin

rifampin(an

(an

inducer of the enzyme)

•• lengthened if taken with erythromycin(an

lengthened if taken with erythromycin(an
inhibitor of the enzyme)

inhibitor of the enzyme)

•• Adverse effects: Headaches, dizziness,

Adverse effects: Headaches, dizziness,
nervousness

nervousness

•• Disadvantage:

Disadvantage: Buspirone

Buspirone has the slow onset

has the slow onset

of action

Hydroxyzine

Hydroxyzine:: is an antihistamine with

is an antihistamine with

antiemetic activity. It has a low tendency for

antiemetic activity. It has a low tendency for
habituation and, thus, is useful for patients with

habituation and, thus, is useful for patients with
anxiety who have a history of drug abuse. It is

anxiety who have a history of drug abuse. It is
also often used for sedation prior to dental

also often used for sedation prior to dental
procedures or surgery. Drowsiness is a possible

procedures or surgery. Drowsiness is a possible
adverse effect

adverse effect

Hydroxyzine

Hydroxyzine:: is an antihistamine with

is an antihistamine with

antiemetic activity. It has a low tendency for

antiemetic activity. It has a low tendency for
habituation and, thus, is useful for patients with

habituation and, thus, is useful for patients with
anxiety who have a history of drug abuse. It is

anxiety who have a history of drug abuse. It is
also often used for sedation prior to dental

also often used for sedation prior to dental
procedures or surgery. Drowsiness is a possible

procedures or surgery. Drowsiness is a possible
adverse effect

adverse effect

Antidepressants:

Antidepressants: many antidepressants have

many antidepressants have

proven efficacy in managing the long

proven efficacy in managing the long--term

term

symptoms of chronic anxiety disorders and

symptoms of chronic anxiety disorders and
should be considered as first

should be considered as first--line agents,

line agents,

especially in patients with concerns for

especially in patients with concerns for
addiction or dependence or a history of

addiction or dependence or a history of
addiction or dependence to other substances.

addiction or dependence to other substances.

The SSRIs, TCAs,

The SSRIs, TCAs, venlafaxine

venlafaxine,, duloxetine

duloxetine and

and

MAOIs all have potential usefulness in treating

MAOIs all have potential usefulness in treating
anxiety

anxiety

Antidepressants:

Antidepressants: many antidepressants have

many antidepressants have

proven efficacy in managing the long

proven efficacy in managing the long--term

term

symptoms of chronic anxiety disorders and

symptoms of chronic anxiety disorders and
should be considered as first

should be considered as first--line agents,

line agents,

especially in patients with concerns for

especially in patients with concerns for
addiction or dependence or a history of

addiction or dependence or a history of
addiction or dependence to other substances.

addiction or dependence to other substances.

The SSRIs, TCAs,

The SSRIs, TCAs, venlafaxine

venlafaxine,, duloxetine

duloxetine and

and

MAOIs all have potential usefulness in treating

MAOIs all have potential usefulness in treating
anxiety

anxiety

••

Other Hypnotic Agents

Zolpidem

•• Is not a benzodiazepine in structure,

Is not a benzodiazepine in structure, but it

but it

acts on a subset of the benzodiazepine

acts on a subset of the benzodiazepine
receptor family, BZ

receptor family, BZ

•• Zolpidem

Zolpidem has no anticonvulsant or muscle

has no anticonvulsant or muscle--

relaxing properties

••

Other Hypnotic Agents

Zolpidem

•• Is not a benzodiazepine in structure,

Is not a benzodiazepine in structure, but it

but it

acts on a subset of the benzodiazepine

acts on a subset of the benzodiazepine
receptor family, BZ

receptor family, BZ

•• Zolpidem

Zolpidem has no anticonvulsant or muscle

has no anticonvulsant or muscle--

relaxing properties

•• It shows few withdrawal effects, and minimal

It shows few withdrawal effects, and minimal
rebound insomnia, and little or no tolerance

rebound insomnia, and little or no tolerance
occurs with prolonged use.

occurs with prolonged use.

•• Zolpidem

Zolpidem is rapidly absorbed from the

is rapidly absorbed from the

gastrointestinal tract, and it has a rapid onset

gastrointestinal tract, and it has a rapid onset
of action and short elimination half

of action and short elimination half--life (about

life (about

2 to

to 3

3 hours).

hours).

•• It shows few withdrawal effects, and minimal

It shows few withdrawal effects, and minimal
rebound insomnia, and little or no tolerance

rebound insomnia, and little or no tolerance
occurs with prolonged use.

occurs with prolonged use.

•• Zolpidem

Zolpidem is rapidly absorbed from the

is rapidly absorbed from the

gastrointestinal tract, and it has a rapid onset

gastrointestinal tract, and it has a rapid onset
of action and short elimination half

of action and short elimination half--life (about

life (about

2 to

to 3

3 hours).

hours).

•

Zolpidem

Zolpidem undergoes hepatic oxidation by the

undergoes hepatic oxidation by the cytochrome

cytochrome

P450

450 system to inactive products.

system to inactive products.

••

Drugs such as

Drugs such as rifampin

rifampin, which induce this enzyme system,

, which induce this enzyme system,

shorten the half

shorten the half--life of

life of zolpidem

zolpidem,,

••

Drugs that inhibit the CYP

Drugs that inhibit the CYP3

4 isoenzyme

isoenzyme may increase the half

may increase the half--

life this drug.

•• Adverse effects of

Adverse effects of zolpidem

zolpidem include

include

nightmares, agitation, headache,

nightmares, agitation, headache,
gastrointestinal upset, dizziness, and daytime

gastrointestinal upset, dizziness, and daytime
drowsiness.

drowsiness.

Ramelteon

Ramelteon::

is a selective agonist at the MT

and MT

subtypes

of melatonin receptors

Stimulation of MT

and MT

receptors by melatonin the

hypothalamus is able to induce and promote sleep

Ramelteon

Ramelteon::

is a selective agonist at the MT

and MT

subtypes

of melatonin receptors

Stimulation of MT

and MT

receptors by melatonin the

hypothalamus is able to induce and promote sleep

Ramelteon

Ramelteon is indicated for the treatment of

is indicated for the treatment of

insomnia in which falling asleep (increased

insomnia in which falling asleep (increased
sleep latency) is the primary complaint.

sleep latency) is the primary complaint.

The potential for abuse of

The potential for abuse of ramelteon

ramelteon is minimal,

is minimal,

and no evidence of dependence or withdrawal

and no evidence of dependence or withdrawal
effects has been observed. Therefore,

effects has been observed. Therefore,
ramelteon

ramelteon can be administered long

can be administered long--term.

term.

Ramelteon

Ramelteon is indicated for the treatment of

is indicated for the treatment of

insomnia in which falling asleep (increased

insomnia in which falling asleep (increased
sleep latency) is the primary complaint.

sleep latency) is the primary complaint.

The potential for abuse of

The potential for abuse of ramelteon

ramelteon is minimal,

is minimal,

and no evidence of dependence or withdrawal

and no evidence of dependence or withdrawal
effects has been observed. Therefore,

effects has been observed. Therefore,
ramelteon

ramelteon can be administered long

can be administered long--term.

term.

•• Adverse effects of

Adverse effects of ramelteon

ramelteon include

include

dizziness, fatigue .

•• Ramelteon

Ramelteon may also increase

may also increase prolactin

prolactin

levels.

•• Adverse effects of

Adverse effects of ramelteon

ramelteon include

include

dizziness, fatigue .

•• Ramelteon

Ramelteon may also increase

may also increase prolactin

prolactin

levels.

Chloral hydrate

•• The drug is an effective sedative and

The drug is an effective sedative and
hypnotic that

hypnotic that

•• Induces sleep in about

Induces sleep in about 30

30 minutes and the

minutes and the

duration of sleep is about

duration of sleep is about 6

6 hours.

hours.

•• Chloral hydrate is irritating to the

Chloral hydrate is irritating to the
gastrointestinal tract and causes

gastrointestinal tract and causes epigastric

epigastric

distress

•• It also produces an unusual, unpleasant taste

It also produces an unusual, unpleasant taste
sensation.

sensation.

•• It synergizes with ethanol

It synergizes with ethanol

Chloral hydrate

•• The drug is an effective sedative and

The drug is an effective sedative and
hypnotic that

hypnotic that

•• Induces sleep in about

Induces sleep in about 30

30 minutes and the

minutes and the

duration of sleep is about

duration of sleep is about 6

6 hours.

hours.

•• Chloral hydrate is irritating to the

Chloral hydrate is irritating to the
gastrointestinal tract and causes

gastrointestinal tract and causes epigastric

epigastric

distress

•• It also produces an unusual, unpleasant taste

It also produces an unusual, unpleasant taste
sensation.

sensation.

•• It synergizes with ethanol

It synergizes with ethanol

Antihistamines:

Antihistamines: diphenhydramine

diphenhydramine

•• They are effective in treating mild types of

They are effective in treating mild types of
insomnia.

insomnia.

•• They have numerous undesirable side effects

They have numerous undesirable side effects
(such as

(such as anticholinergic

anticholinergic effects) that make

effects) that make

them less useful than the benzodiazepines.

Antihistamines:

Antihistamines: diphenhydramine

diphenhydramine

•• They are effective in treating mild types of

They are effective in treating mild types of
insomnia.

insomnia.

•• They have numerous undesirable side effects

They have numerous undesirable side effects
(such as

(such as anticholinergic

anticholinergic effects) that make

effects) that make

them less useful than the benzodiazepines.