4-Anxiolytics and hypnotics drugs
A-Intro
1- Anxiolytic: Reduce anxiety
Sedative : decrease activity, calming effect
Hypnotic : induce sleep
2- Anxiety is a normal fear response to threatening stimuli—>
In severe cases fear reactions occurs in an anticipatory
manner, independently of external events
3- Manifestations of anxiety:
‣ Verbal complaints: The pati say that they are anxious
‣ Somatic and autonomic effects: patis are restless and agitated, tachycardia, increased
sweating, weeping and often GIS disorder
‣ Social effects: Interfere with the normal productive activities.
4- Anxiety disorders
Sedative hypnotic
Benzodiazepines Barbiturates
GABAergic System
B- Drugs
1- Classes of anxiolytic drugs
2- Benzodiazepines (BDZs)
, ‣ Act selectively on GABA^A Receptors
‣ GABA system: The major inhibitory NT in the brain. It has regulates the entrance of CL to the
postsynaptic cells through some speci c receptors on CL channels of the post synaptic neuron.
‣ BDZs act as a positive allosteric modulators by enhancing GABA^A
receptor channel gating in the presence of GABA . It also increase the
frequency of channel opening -> both actions increase CL in ux. THEY
DON”T ACTIVATE GABA^A RECEPTORS IF GABA IS ABSENT.
‣ GABA receptors
• Subunits:
◦α1: Sedative // hypnotic // anticonvulsant //
amnestic effect // addictive.
◦α2: Anxiolytic effect // Muscle relaxation
◦α3: muscle relaxation //
◦α5: muscle relaxation // amnestic effect
‣ Peripheral BDZ Binding sites: present in many tissues and are not
associated with GABA receptors. The target here is a translocater
protein in the mitochondria membranes.
‣ Pharmacokinetics:
• Orally ( well absorbed ), transmucosal, Rectal, IV, IM.
• Highly protein bound ( 60-95%, few signi cant interactions tho ), high lipid solubility
( accumulate in fat and has a high CNS entry rate )
• They undergo microsomal oxidation by CYP3A4 ( N-dealkylation and aliphatic hydroxylation)
A-Intro
1- Anxiolytic: Reduce anxiety
Sedative : decrease activity, calming effect
Hypnotic : induce sleep
2- Anxiety is a normal fear response to threatening stimuli—>
In severe cases fear reactions occurs in an anticipatory
manner, independently of external events
3- Manifestations of anxiety:
‣ Verbal complaints: The pati say that they are anxious
‣ Somatic and autonomic effects: patis are restless and agitated, tachycardia, increased
sweating, weeping and often GIS disorder
‣ Social effects: Interfere with the normal productive activities.
4- Anxiety disorders
Sedative hypnotic
Benzodiazepines Barbiturates
GABAergic System
B- Drugs
1- Classes of anxiolytic drugs
2- Benzodiazepines (BDZs)
, ‣ Act selectively on GABA^A Receptors
‣ GABA system: The major inhibitory NT in the brain. It has regulates the entrance of CL to the
postsynaptic cells through some speci c receptors on CL channels of the post synaptic neuron.
‣ BDZs act as a positive allosteric modulators by enhancing GABA^A
receptor channel gating in the presence of GABA . It also increase the
frequency of channel opening -> both actions increase CL in ux. THEY
DON”T ACTIVATE GABA^A RECEPTORS IF GABA IS ABSENT.
‣ GABA receptors
• Subunits:
◦α1: Sedative // hypnotic // anticonvulsant //
amnestic effect // addictive.
◦α2: Anxiolytic effect // Muscle relaxation
◦α3: muscle relaxation //
◦α5: muscle relaxation // amnestic effect
‣ Peripheral BDZ Binding sites: present in many tissues and are not
associated with GABA receptors. The target here is a translocater
protein in the mitochondria membranes.
‣ Pharmacokinetics:
• Orally ( well absorbed ), transmucosal, Rectal, IV, IM.
• Highly protein bound ( 60-95%, few signi cant interactions tho ), high lipid solubility
( accumulate in fat and has a high CNS entry rate )
• They undergo microsomal oxidation by CYP3A4 ( N-dealkylation and aliphatic hydroxylation)
