5. BARBITURATES
Are CNS depressants which produce effects rangingfrom
Hypnosis
Sedation
and
Reduction of anxiety
Unconsciousness.
Barbiturates were in the past the mainstayof treatment.
7. MECHANISM OFACTION
GABAthe major inhibitory neurotransmitter in the
brain.
It has specific receptors in chloridechannels present
on the membrane of post synapticneurons.
regulates theentrance
of chloride into the
postsynapticcells.
8. MECHANISM OFACTION
Binding of GABA to its receptor (GABA A receptor)
Results in opening of thechloride channel and
Increased conductance of cl¯ ions to insidethe
post-synaptic neuron. hyperpolarization of the
postsynaptic neuronand
decreased synapticneurotransmission.
9. MECHANISM OF ACTION
Barbituratesincreases the cl¯ ion channel opening
(at higher doses open cl¯ ion channels and block Na+
channels)
Increased conductance of cl¯ ions to insidethe
post-synaptic neuron. hyperpolarization of the
postsynaptic neuronand
decreased synapticneurotransmission.
10. PHARMACOLOGICALACTIONS
At Low Doses :
Barbiturates produce sedation
At Higher Doses :
Produce hypnosis Anaesthesia.
Overdosage may cause respiratory
depression and death.
11. USES
ANTICONVULSANT: Phenobarbitone. (tonic-cronic seizures
and eclampsia)
INDUCTION OF ANESTHESIA: thiopentone and
methohexitone.
HYPNOTIC: pentobarbital (used as sleeping pills).
HYPERBILIRUBINEMIA : pentobarbital
To lower serum bilirubin :
a) Patients with chronic cholestasis
b) Neonatal jaundice (kernicterus)
12. ADVERSE EFFECTS
Respiratory depression.
Hangover: residual sedation after awakening.
Tolerance.
Physical dependence with prolonged use.
Teratogenicity.
Allergic reaction: urticaria and skin rash.
Toxicity : Respiratory depression, Cardiovascular collapse, coma
and death.
13. BENZODIZEPINES
The most widely used anxiolyticdrugs.
They have largely replaced barbiturates inthe
treatment of anxiety,
Since
BZs are more effective andsafer.
BZs inducesleep when given in highdoses at
night.
provide sedation.
reduce anxiety when given in low,divided
doses during theday.
15. MECHANISM OF ACTION
GABAthe major inhibitory neurotransmitter in the
brain.
It has specific receptors in chloridechannels present
on the membrane of postsynaptic neurons.
regulates theentrance
of chloride into the
postsynapticcells.
16. MECHANISM OF ACTION
BZs bind to specific, high affinity BZreceptors
present in CNS.
These receptors are separate but adjacent to the
receptor forGABA.
The binding of BZ enhances the affinityof the
GABA receptors for GABAneurotransmitter.
Resulting in a more frequent opening ofadjacent
chloridechannels.
The increased influx of Cl- into the neuronresults
in enhanced.
Hyperpolarization and inhibition of neuronal
firing
17. Therapeutic uses
ANXIETY DISORDERS : alprazolam, lorazepam,
lorazepam, diazepam and chlordiazepoxide.
Alprazolam has anxiolytic-antidepressant effect.
Diazepam is preferred in acute panic-anxiety.
Chlordiazepoxide is preferred in chronic anxiety states.
18. Therapeutic uses
INSOMNIA : in ability to sleep.
Triazolam, lorazepam is effective in treating individuals
who have difficulty in going sleep.
Flurazepam, temazepam & nitrazepam is useful for
insomnia caused by inability to stay asleep.
19. Therapeutic uses
To control withdrawal symptoms of alcohols
diazepam- chlordiazepoxide.
Anticonvulsants:
Diazepam – Lorazepam: Status epilepticus
Clonazepam-Clorazepate: in chronic treatment of epilepsy.
Muscle relaxation: in spastic states (Diazepam) .
23. Structure Activity Relationship (SAR) of
Barbiturates
• 1)Both hydrogen atoms in position 5 of
barbituric acid must be replaced for
maximal activity.
2)Increasing the length of an alkyl chain in the 5
position enhances potency up to 5 or 6 carbon
atoms.
3)Branched, cyclic or unsaturated in the 5 position
generally produce a briefer duration of action than
do normal saturated chains containing the same
number of carbon atoms.
24. 4)Compounds with alkyl groups in the 1 or 3
position may have a shorter onset & duration of
action.
5)Replacement of oxygen by sulfur on the 2 carbon
shortens onset & duration of action.
These are the Structure-Activity-Relationship of
barbiturates.
25.
26. SAR of benzodiazepines
1.The presence of an electron attracting
substituent at position 7 is required for activity
2. Position 6,8 and 9 should not be substituted .
3.A phenyl group at the 5 position promotes activity if
this group is orthoor di ortho substituted with electron
attracting groups , activity is increased.
On the other hand ,para substitution decreases activity
greatly.
5.The 2 carbonyl function is optimal for activity as in
the nitrogen atom at 1 position .
6.The N-substituent should be small .
