2009

ANXIOLYTIC AND HYPNOTIC DRUGS

Anxiety disorders as recognised clinically include:
• generalised anxiety disorder (an ongoing state of excessive
anxiety lacking any clear reason or focus)
• panic disorder (sudden attacks of overwhelming fear occur in
association with marked somatic symptoms, such as
sweating, tachycardia, chest pains, trembling and choking).
• phobias (strong fears of specific objects or situations, e.g.
snakes, open spaces, flying, social interactions)
• post-traumatic stress disorder (anxiety triggered by recall of
past stressful experiences)
• obsessive compulsive disorder (compulsive ritualistic
behaviour driven by irrational anxiety, e.g. fear of
contamination).

It should be stressed that the treatment of such disorders

generally involves psychological approaches as well as drug
treatment.

CLASSIFICATION OF ANXIOLYTIC AND HYPNOTIC DRUGS

The main groups of drugs are as follows:

1. Benzodiazepines.
2. Buspirone.
3. Barbiturates
4. β-Blockers
5. Sedative antihistamines
6. Antidepressants
7. antiepileptic drugs
8. Zolpidem.( for insomnia)

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Benzodiazepines. This is the most important group, used as anxiolytic and
hypnotic agents. Anxiolytics, particularly the benzodiazepines, have
been termed ‘minor tranquillisers’.
1. Buspirone. This 5-HT1A receptor agonist is
anxiolytic but not appreciably sedative.
2. β-Adrenoceptor antagonists (e.g.
propranolol ) These are used to treat some
forms of anxiety, particularly where physical
symptoms such as sweating, tremor and
tachycardia are troublesome. Their
effectiveness depends on block of peripheral
sympathetic responses rather than on any
central effects. They are sometimes used by
actors and musicians to reduce the symptoms
of stage fright.
3. Barbiturates. These are now largely
obsolete, superseded by benzodiazepines.
Their use is now confined to anaesthesia and
the treatment of epilepsy .
4.
5. Sedative antihistamines such as
diphenhydramine & promethazine, are
sometimes used as sleeping pills, intended to
improve children's sleep patterns.they have
antagonistic effect on H1 –receptor in the
brain.
6.
7. Antidepressants as Selective serotonin
reuptake inhibitors such as fluoxetine and
sertraline are used to treat certain anxiety
disorders.Their action in this context appears
to be independent of their antidepressant
effects.
8.
9. Various drugs that enhance the effects of
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 GABA, developed primarily as antiepileptic
drugs ,may also be effective in treating
anxiety disorders ,They include gabapentin ,
and valproate.
10.
11. Zolpidem. This hypnotic acts similarly
to benzodiazepines, although
chemically distinct, but lacks
appreciable anxiolytic activity.It is
approved for the short-term (usually
about two to six weeks) treatment
of insomnia.
Benzodiazepines
Benzodiazepines cause:
1. reduction of anxiety and aggression
2.sedation, leading to improvement of insomnia Although { long-term
use of benzodiazepines as sleeping pills is undesirable, owing to

tolerance, dependence and 'hangover' effects}.

.
3 Benzodiazepines decrease the time taken to get to sleep, and increase
the total duration of sleep, Both effects tend to decline when
benzodiazepines are taken regularly for 1-2 weeks. Long-acting drugs
such as nitrazepam are no longer used as hypnotics.
4.muscle relaxation and loss of motor coordination ( clonazepam)
5.suppression of convulsions (antiepileptic effect) (e.g.
Clonazepam , diazepam ).
Side effects of benzo..
These may be divided into:
1. toxic effects resulting from acute overdosage
2. unwanted effects occurring during normal therapeutic use
3. tolerance and dependence
4. the appearance of a benzodiazepine withdrawal syndrome when the
benzodiazepines are stopped or the dose is reduced after long-term usage.
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 • The withdrawal symptoms may include anxiety & irritability
• sweating
• tremor
• sleep disorders
Side effects of benzo..
1. Drowsiness & confusion
2. amnesia .
3. impaired coordination, which considerably affects manual skills such as
driving performance.

Buspirone
Buspirone is a partial agonist at 5-HT1A receptors is used to treat various anxiety
disorders. It also binds to dopamine receptors, but it is likely that its 5-HT-related
actions are important in relation to anxiety suppression (e.g. ipsapirone).

However, buspirone takes days or weeks to produce its effect in humans,.

Buspirone is ineffective in controlling panic attacks or severe anxiety states.

Buspirone has side effects quite different from those of benzodiazepines. It does
not cause sedation or motor incoordination, nor have withdrawal effects been
reported.

side effects are nausea, dizziness, headache and restlessness, which generally seem
to be less troublesome than the side effects of benzodiazepines.

BARBITURATES

Barbiturates that remain in clinical use include phenobarbital, still occasionally

used to treat epilepsy ,and thiopental, which is widely used as an intravenous
anaesthetic agent . use as sedative/hypnotic agents is no longer recommended.
Barbiturates are Non-selective central nervous system depressants that produce
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effects ranging from sedation and reduction of anxiety to unconsciousness and
death from respiratory and cardiovascular failure-therefore dangerous in
overdose.
Act partly by enhancing action of GABA, but less specific than benzodiazepines.

Barbiturates induce a high degree of tolerance and dependence. They also strongly
induce the synthesis of hepatic cytochrome P450 and conjugating enzymes, and
thus increase the rate of metabolic degradation of many other drugs.
OTHER POTENTIAL ANXIOLYTIC DRUGS
Antidepressants: Selective serotonin reuptake inhibitors
such as fluoxetine and sertraline are used to treat certain
anxiety disorders( including obsessive compulsive disorder
and panic). Their action in this context appears to be
independent of their antidepressant effects.

antiepileptic drugs : Various drugs that enhance the effects of GABA,

developed primarily as antiepileptic drugs ,may also be effective in treating
anxiety disorders ,They include gabapentin, and valproate.

Drug interaction with anxiolytic or

hypnotic drugs
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Corticosteroids
barbiturates accelerate metabolism of corticosteroids
.
Coumarins

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barbiturates accelerate metabolism of coumarins .

Digitoxin
barbiturates accelerate metabolism of digitoxin .
Doxycycline
barbiturates accelerate metabolism of doxycycline .
Metronidazole
barbiturates accelerate metabolism of metronidazole .
Progestogens &oestrogenes
barbiturates accelerate metabolism of prog& oestro..( reduced
contraceptive
effect(

Propranolol
barbiturates possibly reduce plasma concentration of propranolol
Clonazepam
phenobarbital often reduces plasma concentration of clonazepam
Folates
plasma concentration of phenobarbital possibly reduced by folates
Rifampicin
phenobarbital possibly reduces plasma concentration of rifampicin
Valproate
plasma concentration of phenobarbital increased by valproate (also plasma
concentration of valproate reduced)
Alcohol
increased sedative effect when barbiturates given
with alcohol .

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Notes on hypnotics ('sleeping tablets') :

The cause of insomnia should be established before

administering hypnotic drugs. Common causes
include alcohol or other drug misuse and physical or
psychiatric disorder (especially depression).
Tricyclic antidepressants cause drowsiness, so can
kill two birds with one stone if taken at night by
depressed patients with sleep disturbance.
Optimal treatment of chronic insomnia is often by
changing behaviour (e.g. increasing exercise,
staying awake during the day) rather than with
drugs.

sedatives /anxiolytics and dental procedures

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Some anxious patients may benefit from the use of a hypnotic for
1 to 3 nights before the dental appointment. Hypnotics do not
relieve pain, and if pain interferes with sleep an appropriate
analgesic should be given. Diazepam , nitrazepam or
temazepam are used at night for dental patients. Temazepam is
preferred when it is important to minimise any residual effect the
following day.
Diazepam and temazepam are effective anxiolytics for dental
treatment in adults, but they are less suitable for children.
Diazepam has a longer duration of action than temazepam. When
given at night diazepam is associated with more residual effects
the following day; patients should be very carefully warned not to
drive .

In children anxiolytic treatment should be used only to relieve

acute anxiety (and related insomnia) caused by fear (e.g. before
surgery).
Benzodiazepines can alleviate anxiety at doses that do not
necessarily cause excessive sedation and they are of particular
value during short procedures or during operations under local
anaesthesia (including dentistry). Amnesia reduces the likelihood
of any unpleasant memories of the procedure .
Benzodiazepines have no analgesic effect so an opioid analgesic
may sometimes be required for pain.

Anxiolytics diminish tension, anxiety and panic,

and may benefit anxious patients. However, their
use is no substitute for sympathy and reassurance
of the patient.

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