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Anxiety
An unpleasant state of tension,
apprehension or uneasiness.
Anxiolytic & A fear that seems to arise from
an unknown source.
Hypnotic Drugs

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Xanor
Severe Anxiety Symptoms Librium, Solium
Similar to those of fear such as: Rivotril Doral
Tachycardia Tranxene-SD
Sweating Serax
Trembling Valium
Restoril
Palpitations Prosom, Tasedan
and involve sympathetic activation. Halcion
Dalmane

Episodes of mild anxiety are common Ativan

life experiences and do not warrant
treatment, but severe ones needs to
BENZODIAZEPINES – most widely used anxiolytic drugs.
be treated with anti-anxiety drugs or
Replaced barbiturates and meprobamate in the tx of
psychotherapy.
ANXIETY because they are safer and more effective.

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BENZODIAZEPINES BENZODIAZEPINES
Targets for Benzodiazepine actions are
GABAA receptors. (GABAA composes of
alpha, beta and gamma subunit families.)

MOA: Benzodiazepines potentiate the effect

of GABA by binding to a specific GABA
receptor resulting in greater entry of
chloride ion and leads to an increase in
chloride conductance.

BZD increase the frequency of channel

openings.

Influx of chloride ions produces membrane

hyperpolarization inducing neuronal
inhibition.
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BENZODIAZEPINES BENZODIAZEPINES
Some commonly used Benzodiazepine drugs:

Alprazolam (Xanor)
Bromazepam (Lexotan)
Chlordiazepoxide (Solium, Librium)
Clonazepam (Rivotril)
Clorazepate (Tranxene-SD)
Diazepam (Valium)
Estazolam (ProSom, Tasedan)
Flurazepam (Dalmane)

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BENZODIAZEPINES BENZODIAZEPINES
Some commonly used Benzodiazepine drugs: ACTIONS: They have neither antipsychotic
activity nor analgesic actions, and they do
not affect the ANS. All benzodiazepines
Lorazepam (Ativan)
exhibit the following actions to a greater or
Midazolam (Dormicum) lesser extent:
Quazepam (Doral)
Oxazepam (Serax) 1. Reduction of Anxiety. At low doses, the
Temazepam (Restoril) benzodiazepines are anxiolytic;
selectively enhance GABAergic
Triazolam (Halcion)
transmission in neurons with the Alpha2
subunit in their GABAA receptors
inhibiting neuronal circuits in the limbic
system of the brain.
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BENZODIAZEPINES
ACTIONS:
2. Sedative and hypnotic actions. All
benzodiazepines have sedative properties
and produce hypnosis at higher doses.
3. Anterograde amnesia. Impairs memory
temporarily and inability to learn and form
new memories.
4. Anticonvulsant. Used to treat epilepsy.
5. Muscle relaxant. At high doses, they
relaxes the spasticity of skeletal muscle by
increasing presynaptic inhibition in the
spinal cord. (Baclofen)
BENZODIAZEPINES
THERAPEUTIC USES:
1. Anxiety disorders. Effective for the tx of
anxiety symptoms secondary to panic
disorder, GAD, SAD, performance
anxiety, PTSD, OCD and extreme anxiety
sometimes encountered with specific
phobias such as fear of flying.
• Panic disorder with agoraphobia is an
anxiety in which a person has attacks of
intense fear and anxiety.
• Also used for depression and
schizophrenia

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BENZODIAZEPINES
THERAPEUTIC USES:
1. Anxiety disorders. Longer acting agents –
Clonazepam, Lorazepam and Diazepam.
Ø Preferred for patients with anxiety that
may require treatment for prolonged
periods of time.
Ø TOLERANCE à decreased
responsiveness to repeated doses of
drugs, occurs for more than 1-2 weeks.
Ø CROSS-TOLERANCE à exists among
group of agents with ethanol.
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BENZODIAZEPINES
THERAPEUTIC USES:
3. Amnesia.
Shorter-acting agents are employed as
premedication for anxiety provoking
procedures. Midazolam is an injectable
benzodiazepine used for the induction of
anesthesia.
4. Seizures.
Used to treat epilepsy. Clonazepam,
Clorazepate, Diazepam and
Lorazepam are used in the tx of
certain convulsive (seizure) disorders.
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BENZODIAZEPINES
THERAPEUTIC USES:
5. Sleep disorders.
Nonbenzodiazepines DO NOT
significantly alter the various sleep stages
and are often the preferred HYPNOTICS.
Flurazepam - causes little rebound
insomnia. Half-life is approx. 85 hours.
Triazolam – short-duration of action, to
induce sleep in patients with recurring
insomnia.
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BENZODIAZEPINES
THERAPEUTIC USES:
1. Anxiety disorders.
Alprazolam, for panic disorders, is
effective for short- and long-term
treatment but may cause withdrawal
reactions in about 30% of sufferers.
2. Muscular disorders. Diazepam is used to
relieve muscle spasms. Diazepam
injection is used before some medical
procedures to relieve anxiety and to
reduce memory of the procedure. Also
used for treating multiple sclerosis and
cerebral palsy.
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BENZODIAZEPINES
THERAPEUTIC USES:
4. Seizures.
Diazepam and Lorazepam – DOC in grand
mal epileptic seizures and status epilepticus.
Chlordiazepoxide, Clorazepate, Diazepam
and Oxazepam – useful in acute tx of alcohol
withdrawal and reducing the risk of
withdrawal-related seizures.
5. Sleep disorders.
Long-acting Flurazepam, intermediate acting
Temazepam and short-acting Triazolam are
the most prescribed benzodiazepine.
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BENZODIAZEPINES
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Frequency of rebound insomnia
resulting from discontinuation
of benzodiazepine therapy.
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BENZODIAZEPINE ANTAGONIST
FLUMAZENIL
ADR:
Administration of Flumazenil may precipitate
withdrawal in dependent patients or cause
seizures if a benzodiazepine is used to control
seizure activity.
Common ADR: Dizziness, nausea, vomiting,
and agitation
CI: Seizures may also result if the patient
ingests tricyclic antidepressants.
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OTHER ANXIOLYTIC DRUGS
Buspirone
ØUseful in the chronic treatment of generalized
anxiety disorder and has an efficacy comparable to
that of the benzodiazepines.
ØMOA: Action of buspirone is mediated by
serotonin (5-HT1A) receptors, although other
receptors could be involved, because buspirone
displays some affinity for DA2 dopamine receptors
and 5-HT 2A serotonin receptors.
ØBuspirone lacks the anticonvulsant and muscle-
relaxant properties of the benzodiazepines and
causes only minimal sedation.
ØDisadvantage: slow onset of action.
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BENZODIAZEPINE ANTAGONIST
FLUMAZENIL
ØA GABA receptor antagonist that can rapidly
reverse the effects of benzodiazepines.
PHARMACOKINETICS
ØAvailable for intravenous administration only.
ØOnset is rapid but duration is short, with a
half-life of about 1 hour.
ØFrequent administration may be necessary
to maintain reversal of a long-acting
benzodiazepine.
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OTHER ANXIOLYTIC DRUGS
Hydroxyzine (ITERAX)
> An antihistamine with antiemetic activity.
ØLow tendency for habituation
ØUseful for patients with anxiety who have a history
of drug abuse
ØPossible ADR: Drowsiness
Antidepressants
ØHave proven efficacy in managing the long-term
symptoms of chronic anxiety disorders.
ØConsidered as first-line agents, especially in
patients with concerns for addiction or dependence
or a history of addiction or dependence to other
substances.
ØThe SSRIs and SNRIs have potential usefulness
in treating anxiety.
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BARBITURATES
MOA:
ØSedative-hypnotic action of the barbiturates
is due to their interaction with GABAA
receptors, which enhances GABAergic
transmission.
ØBarbiturates potentiate GABA action on
chloride entry into the neuron by prolonging
the duration of the chloride channel
openings.
ØCan block excitatory glutamate receptors.
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ACTIONS:
ØDepression of CNS:
BARBITURATES
ØAt low doses, the THERAPEUTIC USES:
barbiturates produce
sedation (calming effect, • 1- Anesthesia: The ultra short-acting
reducing excitement). At barbiturates, such as thiopental, are used
higher doses, the drugs intravenously to induce anesthesia.
cause hypnosis, followed by
anesthesia (loss of feeling or
sensation), and finally, coma • 2- Anticonvulsant: Phenobarbital is used
and death. in long-term management of tonic-clonic
ØRespiratory depression:
seizures, status epilepticus, and
Barbiturates suppress the
hypoxic and chemoreceptor
eclampsia.
response to CO2, and
overdosage is followed by
respiratory depression and
death.

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BARBITURATES BARBITURATES
THERAPEUTIC USES: THERAPEUTIC USES:
• 2- Anticonvulsant: • 3- Anxiety: Barbiturates have been used
as mild sedatives to relieve anxiety,
nervous tension, and insomnia. However,
• Phenobarbital has been regarded as the
most have been replaced by the
drug of choice for treatment of young
benzodiazepines.
children with recurrent febrile seizures.
However, Phenobarbital can depress
cognitive performance in children, and the
drug should be used cautiously.

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BARBITURATES ADR OF BARBITURATES

PHARMACOKINETICS:
Barbiturates
Ø absorbed orally
Ø distributed widely throughout the body
Ø readily cross the placenta and can
depress the fetus
Ø metabolized in the liver, and inactive
metabolites are excreted in the urine

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Preferred Hypnotics NONBENZODIAZEPINES

(Nonbenzodiazepines, Z drugs) (Z-DRUGS)
Nonbenzodiazepines, although, chemically
A. ZOLPIDEM (STILNOX) distinct from benzodiazepines, operate
B. ZALEPLON very similarly upon GABA receptors. The
C. ESZOPICLONE only significant difference between these
D. RAMELTEON two classes of drugs is that
E. CHLORAL HYDRATE nonbenzodiazepines have a much shorter
F. ANTIHISTAMINES half-life than most benzodiazepines.
G. ETHANOL
Zolpidem (Stilnox)
Zaleplon (Sonata)
Zopiclone (Zimovane, Imovane)
Eszopiclone (Lunesta)
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THANK YOU!

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