Pharmacology. 14-15/03/20
Anxiolytics & Hypnotics
1. Outline
What is anxiety and cover clinically recognised anxiety disorders
Chemical mediators involved
- GABA
- 5-HT
- NA
Therapeutics used that target those pathways
Insomnia & therapeutics involve
2. Anxiety
Normal fear response to threatening stimuli
- Autonomic reflexes (Release of NA/A, ↑HR)
- ↑arousal & alertness, Defensive behaviours
- Corticosteroid secretion because of stress
- Negative emotions
Pathology –fear response occurs in anticipation, independent of external events, to the point
that symptoms interfere with normal productive activities
3. Clinically recognised anxiety disorders
Generalised anxiety disorder (GAD) –lifetime prevalence 4-7%, ♀˃♂, linked to deprsion
- ‘The patient must have excessive and difficult to control anxiety about several different
events or activities’ –DSM-IV
- Worry, irritability, insomnia, muscle tension +
- Anticipating future harm
- Planning/predicting –prefrontal cortex
- Basic fear circuit –amygdala
- GABA dysfunction: hyperpolarisation, lost control of feelings
Post-traumatic stress disorder (PTSD)
- Anxiety triggered by recall of past stressful experiences
- Re-experience the trauma, Hyper-arousal, active recalling due to specific triggers
- ↓ Hippocampus activity
Panic disorder -♀˃♂
- sudden attacks of overwhelming fear with somatic symptoms
o Sweating, tachycardia, hyperventilation
- Conditioned fear
o ‘fight or flight’ response –amygdala
o Fear conditioning –hippocampus
o Oversensitive to 5-HT, NA & cortisol
Obsessive compulsive disorder (OCD)–1.2% UK, 50% cases = severe, ♀= ♂
- Obsessions –continually preoccupies mind, ↑ anxiety
- Compulsions –repetitive behaviour/rituals –attempt to ↓ anxiety
- Decision making- pre frontal cortex & basal ganglia
Phobias
- Specific/simple: relates to one thing, develop in childhood
- Complex phobias
o Social phobia/anxiety –specific situation (public speaking) or general socialising
o Agoraphobia –situations/places
, Pharmacology. 14-15/03/20
Anxiolytics & Hypnotics
4. Animal models
How much the mouse spends in open arms than
closed arms, and then how that affects with
anxiolytics (So less fears)
5. Human
Anxiety attack can be induced if co2 inhaled,
and after it, questionnaire and asked about
experience. Better models are needed to
have a better understanding.
6. GABA
↓ GABAA function in brains of GAD patients
Two theories
- GABAA downregulated
- Endogenous anxiogenic–inverse agonist
- Also, less GABA produced
Activation of GABAergic neuron, GABA is
released and at the same time
glutamate then there’s competition.
GABA wins so no anxiety. If less GABA or
less GABA receptors = less Cl- influx
therefore activation by glutamate of
the neuron which will lead to anxiety. We need a drug that will bind to positive modulatory sites to open
GABA channels more = Benzodiazepines.
7. Benzodiazepines (BDZ)
BDZ subunits found
between α and γ
subunit (square), GABA
binds and chloride influx.
BDZ bind increases affinity
of GABA receptor site and
baster opening of the
channel. Therefore, relief
anxiety.
Anxiolytics & Hypnotics
1. Outline
What is anxiety and cover clinically recognised anxiety disorders
Chemical mediators involved
- GABA
- 5-HT
- NA
Therapeutics used that target those pathways
Insomnia & therapeutics involve
2. Anxiety
Normal fear response to threatening stimuli
- Autonomic reflexes (Release of NA/A, ↑HR)
- ↑arousal & alertness, Defensive behaviours
- Corticosteroid secretion because of stress
- Negative emotions
Pathology –fear response occurs in anticipation, independent of external events, to the point
that symptoms interfere with normal productive activities
3. Clinically recognised anxiety disorders
Generalised anxiety disorder (GAD) –lifetime prevalence 4-7%, ♀˃♂, linked to deprsion
- ‘The patient must have excessive and difficult to control anxiety about several different
events or activities’ –DSM-IV
- Worry, irritability, insomnia, muscle tension +
- Anticipating future harm
- Planning/predicting –prefrontal cortex
- Basic fear circuit –amygdala
- GABA dysfunction: hyperpolarisation, lost control of feelings
Post-traumatic stress disorder (PTSD)
- Anxiety triggered by recall of past stressful experiences
- Re-experience the trauma, Hyper-arousal, active recalling due to specific triggers
- ↓ Hippocampus activity
Panic disorder -♀˃♂
- sudden attacks of overwhelming fear with somatic symptoms
o Sweating, tachycardia, hyperventilation
- Conditioned fear
o ‘fight or flight’ response –amygdala
o Fear conditioning –hippocampus
o Oversensitive to 5-HT, NA & cortisol
Obsessive compulsive disorder (OCD)–1.2% UK, 50% cases = severe, ♀= ♂
- Obsessions –continually preoccupies mind, ↑ anxiety
- Compulsions –repetitive behaviour/rituals –attempt to ↓ anxiety
- Decision making- pre frontal cortex & basal ganglia
Phobias
- Specific/simple: relates to one thing, develop in childhood
- Complex phobias
o Social phobia/anxiety –specific situation (public speaking) or general socialising
o Agoraphobia –situations/places
, Pharmacology. 14-15/03/20
Anxiolytics & Hypnotics
4. Animal models
How much the mouse spends in open arms than
closed arms, and then how that affects with
anxiolytics (So less fears)
5. Human
Anxiety attack can be induced if co2 inhaled,
and after it, questionnaire and asked about
experience. Better models are needed to
have a better understanding.
6. GABA
↓ GABAA function in brains of GAD patients
Two theories
- GABAA downregulated
- Endogenous anxiogenic–inverse agonist
- Also, less GABA produced
Activation of GABAergic neuron, GABA is
released and at the same time
glutamate then there’s competition.
GABA wins so no anxiety. If less GABA or
less GABA receptors = less Cl- influx
therefore activation by glutamate of
the neuron which will lead to anxiety. We need a drug that will bind to positive modulatory sites to open
GABA channels more = Benzodiazepines.
7. Benzodiazepines (BDZ)
BDZ subunits found
between α and γ
subunit (square), GABA
binds and chloride influx.
BDZ bind increases affinity
of GABA receptor site and
baster opening of the
channel. Therefore, relief
anxiety.
