Sedative hypnotics.pptx

SEDATIVE
Drugs that calm the patient and reduce anxiety without inducing
normal sleep.

HYPNOTICS
Drugs that produce drowsiness and encourage the
onset of sleep

CLASSIFICATION OF DRUGS
 Barbiturates.
 Benzodiazepines ( BDZ ).
 Miscellaneous agents.
 Buspirone
 Chloral hydrate
 Zolpidem
 Zaleplon.
 zopiclon

BARBITURATES
 Are CNS depressants which produce effects rangingfrom
Hypnosis
 Sedation
and
Reduction of anxiety
Unconsciousness.
 Barbiturates were in the past the mainstayof treatment.

BARBITURATES
Short-acting(3-8h):
• Pentobarbitone
• Secobarbitone
• Amobarbital
Ultrashort acting (25 minutes): Thiopentone, Methohexitone.
Classification:
Long acting( 24-28 h): Phenobarbitone
Intermediate (8-24h): Amylobarbitone
Bayeredicoverer
of barbiturates.

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.

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.

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.

PHARMACOLOGICALACTIONS
At Low Doses :
Barbiturates produce sedation
At Higher Doses :
 Produce hypnosis Anaesthesia.
Overdosage may cause respiratory
depression and death.

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)

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.

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.

BENZODIZEPINES
 Sedative (Anxiolytics) :
Alprazolam
Diazepam
Chlordiazepoxide lorazepam
lorazepam
 Hypnotics :
Triazolam
Lorazepam
Diazepam
Estazolam
Alprazolam
Temazepam
Flurazepam Nitrazepam Quazepam
 Preanesthetics :
Diazepam - Midazolam
Leosternback

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.

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

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.

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.

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) .

Therapeutic uses
InAnesthesia :
Preanesthetic medication diazepam
Induction of balanced anesthesia (Midazolam)

ADVERSE EFFECTS
 Ataxia (motor incoordination), cognitive impairment.
 Hangover, drowsiness, confusion (especially in long acting
drugs)
 Tolerance
 Physical and Psychological dependence (in high doses)
 Withdrawal symptoms (Abrupt discontinuation of BZs)
 Insomnia, anorexia, anxiety, agitation, tremors
and convulsion.(Abrupt discontinuation of BZs)

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.

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.

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 .

Sedative hypnotics.pptx

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