pharmacologyy

2. Benzodiazepines
• History
• Introduction
• Classification
• Mechanism of action
• Therapeutic uses/ Actions
• Pharmacokinetics
• Adverse effects
• Precautions

3. History :
• A benzodiazepine is a psychoactive drug whose core
chemical structure is the fusion of a benzene ring and
a diazepine ring.
• The first benzodiazepine, chlordiazepoxide (Librium),
was discovered accidentally by Leo Sternbach in 1955,
and made available in 1960 by Hoffmann–La Roche,
which has also marketed diazepam (Valium) since 1963.

4.  Benzodiazepines are used primarily in the treatment of :-
 Generalized anxiety
 Panic disorders
 As sedative hypnotics
 As muscle relaxants
 As anticonvulsants
 They largely replaced barbiturates because they're are shown to
have much wider safety margins than barbiturates, thus safer.
 Traditionally they are considered to have a less potential for
addiction and dependence..

5. Classification of Benzodiazepenes
Upon the bases of HALF LIFE
1.Short acting:
Half life is less than 6 hours
Midazolam
Flurazepam
Clorazepate
Triazolam

6. Intermediate Acting
 Half life is 6-24 hours
• Alprazolam
• Estazolam
• Chlordiazepoxide
• Temazepam
Long Acting
 Half life is more than 24
hours
• Diazepam
• Quazepam
• Nitrazepam

7. Sites of BZDs in brain
• The targets for BZDs in brains are the GABA receptors
• GABA receptors are primarily composed of
• 2 α subunits
• 2 β subunits
• 1 γ subunit
• BZDs modulate GABA effects by binding to a specific, high
affinity site located at interface of the
α & γ2 subunits

10. Binding of GABA to its receptors triggers an opening of
chloride channel, which leads to an increase in chloride
conductance.
BZDs increase the frequency of channel opening
produces by GABA.
The influx of chloride ions causes hyperpolarization that
moves the postsynaptic potential away from its firing
threshold , and ,thus inhibits the formation of action
potentials.
Mechanism of Action

14. PHARMACOKINETICS:
• Absorption and distribution :-
BZDs are lipophilic they are rapidly and completely
absorbed after oral administration and distribute
throughout the body .
 Binding:-
Strongly bound to plasma proteins

15. 1-3days
Long acting
10-20hours
Intermediate
acting
3-8hours
Short acting

16. Metabolism:-
Most BZDs including Chlordiazepoxide and diazepam are
metabolized by the hepatic microsomal system to compound that
are also active.
Excretion:-
BZDs are excreted in urine as glucoronides metabolites.

18. Actions
• Reduction of anxiety:-
At low doses BZDs anxiolytic by inhibiting neuronal circuits in limbic system of
brain.. Alprazolam, Lorazepam, Oxazepam, Chlordiazepoxide..
• Sedative & hypnotic actions:-
All of BZDs used to treat anxiety have some sedative properties, and some can
produces hypnosis at high doses.. Diazepam, Flurazepam,
Nitrazepam,Midazolam..
• Anterograde amnesia:-
The temporary loss of memory with the use of benzodiazepam is also mediated
by the α1-GABAa receptors this also impairs a person’s ability to learn and form
a new memory.

19. • Anticonvulsant:-
Several of BZDs have anticonvulsant activity & some are use
to treat epilepsy & seizures disorder
Clonazepam , Diazepam, Clobazam
• Muscle relaxant:-
At high doses, the BZDs relax the spasticity of skeletal
muscle, probably by increasing presynaptic inhibition in spinal
cord, where the α2 GABAa receptors are largely located

20. Side
Effects
•sedation,
•dizziness,
•weakness, and
•unsteadiness.

21.  Acute toxicity: Benzodiazepines in acute overdose are
considerably less dangerous than other sedative-hypnotic drugs.
 Cause prolonged sleep, without serious depression of
respiration or cardiovascular system.
 Severe and even life threatening respiratory depression may
occur in BZD combination with other CNS depressants
particularly ALCOHOL.
 Acute overdose can b counteracted by effective antagonist,
flumazenil.

22. • Side-effects during therapeutic use: Influence of
manual skills: (i.e driving performance) due to drowsiness,
confusion, amnesia, impaired coordination. Main disadvantages
are interaction with alcohol, long-lasting hangover and the
development of dependence.
• Tolerance and dependence: Tolerance may occur with all
BZD.
• Stopping BZD treatment after weeks or months causes an
increase in symptoms of anxiety, together with tremor n
dizziness.

23. Precautions
These drugs should be used cautiously in
treating patients with liver disease
These drugs should be avoided in patients
With acute narrow angle glaucoma…
EFFECTS ON PREGNANCY:-
All the BZD cross the placental
barrier N may depress the CNS of the newborn , can result
In fetal abnormalities n fetal dependence If given before
birth.
Nursing infants can also suffer as BZD are excreted in breast
Milk.

24.  Because of their muscle relaxant action, benzodiazepines may
cause respiratory depression in susceptible individuals. For that reason,
they are contraindicated in people with myasthenia gravis,sleep
apnea, bronchitis, and COPD.
 Caution is required when benzodiazepines are used in people
with personality disorders or mental retardation because of
frequent paradoxical reactions.
 In major depression, they may precipitate suicidal tendencies and are
sometimes used for suicidal overdoses.
 Individuals with a history of alcohol, opioid and barbiturate abuse should
avoid benzodiazepines, as there is a risk of life-threatening interactions
with these drugs