Lec.

1 3 : ‫العدد‬

9112/11/11 ‫االحد‬ ‫أدوية‬ ‫ ابراهيم‬.‫د‬

Drugs Used in Mental Illness
Anxiolytic and Hypnotic Drugs
OR
Sedative-Hypnotic Drugs
 A Sedative-Hypnotic drug is an agent that its major therapeutic
use is to cause sedation (with concomitant relief of anxiety) or to
encourage sleep.

 An effective sedative (anxiolytic) agent should reduce anxiety and

exert a calming effect.

 A hypnotic drug should produce drowsiness and encourage the

onset and maintenance of a state of sleep.

Hypnotic effects involve more pronounced depression of the CNS than

sedation, and this can be achieved with many sedative drugs in this class
simply by increasing the dose.

Anxiety

 It is an unpleasant state of tension, apprehension, or uneasiness

(a fear that arises from either a known or an unknown source).

 Symptoms of severe anxiety are similar to those of fear (such as

tachycardia, sweating, trembling, and palpitations) and involve
sympathetic activation.

 Anxiety is treated with antianxiety drugs (sometimes called

anxiolytics).

 Because many antianxiety drugs can cause sedation and hypnosis,

they may be used as both anxiolytic and hypnotic (sleep-inducing)
agents.

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Benzodiazepines

 Because they are safer and more effective, BZDs replaced

barbiturates and meprobamate for anxiety and insomnia.

 Despite BZDs are commonly used, they are not necessarily the
best choice for anxiety or insomnia.

 Certain antidepressants with anxiolytic action, such as the

selective serotonin reuptake inhibitors (SSRIs), are preferred in
many cases of anxiety, and nonbenzodiazepine hypnotics and
antihistamines may be preferable for insomnia.

Classification

1. Short-acting

The t1/2 is 2-4 hours, e.g. Midazolam, Oxazepam,

and Triazolam.

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2. Intermediate-acting

The t1/2 is 5-10 hours, e.g. Alprazolam, Estazolam, Lorazepam and

Temazepam.

3. Long-acting

The t1/2 is 30-60 hours, e.g. Clonazepam, Clorazepate,

Chlordiazepoxide, Diazepam, Flurazepam, and Quazepam.

Mechanism of action

The targets for BDZ actions are the γ-aminobutyric acid (GABAA)
receptors.

Note: GABA is the major inhibitory neurotransmitter in the central

nervous system (CNS).

 The BZDs do not substitute for GABA but appear to enhance

GABA’s effects (increases the affinity of GABA for the GABA-
binding site) without directly activating GABAA receptors.

{GABA and benzodiazepine + GABAA receptors enhanced influx of

chloride ions hyperpolarization and inhibition of action
potential formation}.

Actions

1. Reduction of anxiety: At low doses, the BZDs are anxiolytic.

2. Sedative/hypnotic: At higher doses, all BZDs have sedative

properties and some can produce hypnosis.

3. Anterograde amnesia: Temporary impairment of memory.

4. Anticonvulsant: Several BZDs have anticonvulsant activity.

5. Muscle relaxant: At high doses, the BZDs relax the spasticity of

skeletal muscle, probably by increasing presynaptic inhibition in
the spinal cord.

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Note: Baclofen is a non-benzodiazepine orally active GABA-mimetic
muscle relaxant that is believed to activates GABA receptors at the level
of the spinal cord.

Therapeutic uses

1. Anxiety disorders:

BZDs are effective for the anxiety symptoms secondary to:

panic disorder, generalized anxiety disorder (GAD), social anxiety

disorder, performance anxiety, post-traumatic stress disorder,
obsessive–compulsive disorder, anxiety associated with phobias, such as
fear of flying and anxiety related to depression and schizophrenia.

• The longer-acting agents are often preferred.

• The antianxiety effects of the BZDs are less subject to tolerance

than the sedative and hypnotic effects.

[Note: Tolerance (that is, decreased responsiveness to repeated doses

of the drug) occurs when used for more than 1 to 2 weeks.

2. Sleep disorders:

 BZDs decrease the latency to sleep onset and increase non-rapid

eye movement (NREM) sleep.

 In the treatment of insomnia, it is important to balance the

sedative effect needed at bedtime with the residual sedation
(“hangover”) upon awakening.

 Commonly prescribed agents include:

a. short-acting triazolam which is effective in treating individuals who

have problems falling asleep.

b. Intermediate-acting temazepam which is useful for patients who

experience frequent awakenings and have difficulty staying asleep.

 Long-acting agents are rarely used for insomnia, because their

extended half-life may results in excessive daytime sedation.

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3. Amnesia:

The shorter-acting agents are often employed as premedication for

anxiety-provoking and unpleasant procedures, such as endoscopy,
dental procedures, and angioplasty.

4. Seizures:

 Clonazepam is used as an adjunctive therapy for certain types of

seizures.

 Lorazepam and diazepam are the drugs of choice in terminating

status epilepticus

 Useful in the acute treatment of alcohol withdrawal and reduce

the risk of withdrawal-related seizures

5. Muscular disorders:

 skeletal muscle spasms (strains).

 spasticity from degenerative disorders, such as multiple sclerosis

and cerebral palsy.

6. Parenteral lorazepam is used to suppress the symptoms of delirium

tremens (rapid onset of confusion usually caused by withdrawal from
alcohol).