Traditional Anxiolytics Flashcards
What are the therapeutic uses of benzodiazepines
Short term sedation
Relieve muscle tension
Anxiolysis (short term)
Hypnosis
Anticonvulsant
What are the side effects of the acute use of benzodiazepines
Undated sedation/drowsiness
Reduced motor co-ordination
Amnesia
Reduced cognition
What are the side effects of chronic use of benzodiazepines
Tolerance
Dependence
Withdrawal syndrome
Why are benzodiazepines useful in hypnosis
Short half life
Person doesn’t wake-up sedated - no day time drowsiness
What type of benzodiazepines are used as anxiolytics
Those that have a long half life
E.g diazepam, lorazepam
Why do some benzodiazepines have a longer half life
Have active metabolites once undergone oxidative metabolism by CYP450s before undergoing conjugation
What receptor do benzodiazepines act upon
GABAa receptor
Allosteric modulation of GABAa R
Why do barbiturates have a small therapeutic window
Bind to GABAa R
But can open the CL- channel in absence of GABA
Reduces excitability of NA+ channels to prevent action
Not allosteric modulator
What controls the endocrine, autonomic and behavioural response in the fear pathway
Endocrine: hypothalamus
Autonomic: locus coeruleus
Behavioural: striatum
What pathway is GABAaR expressed
Fear pathway
Describe the fear pathway in people with anxiety disorders
Decreased binding at benzo site on GABAaR
= decreased benzo complex in anxiety disorders
= fear pathways are more active
What is the most common composition of GABAaR in humans
2 alpha
2 beta
Usually 1 gamma
Subtypes vary in different brain regions
Where is A1 receptors mainly located
Cerebral + cerebellar cortex + basolateral amygdala
Most prevalent subtype
Where are A2 receptors mainly located
Hippocampus + central amygdala + striatum
Where are A3 receptors mainly located
Monoaminergic neurons in brainstem
Basal forebrain cholierngic neurons
Nucleus of thalamus
Describe how the arousal pathway is activated when awake
Suprachiasmatic nucleus -> inhibits the ventrolateral preoptic nucleus -> stops inhibiton of arousal pathways = awake
What 3 areas are involves in the arousal pathway and what do they release
Tuberomammillary nucleus: histamine
Raphe nuclei: 5-HT
Locus coeruleus: Noradrenaline
What is the mechanism of sleep
Pineal gland releases melatonin = inhibits SCN
Build up of adenosine -> activates VLPO nucleus -> inhibits arousal pathways
= sleep
What effect do A1 receptors mediate
Sedation and amnesia
What effect do A2 receptors mediate
Anxiolysis
What effect do A3 receptors mediate
Anxiolysis
What effect do A5 receptors mediate
Learning, memory and muscle relaxation
What receptors subtypes are insensitive to benzo’s and why
A4 and A6
Have an arginine in the corresponding position
Describe tolerance after using benzos
Need more to get the same therapeutic effect
Secondary neurone adaptations = synaptic plasticity
Reduce the expression of GABAaR with a high affinity
Describe withdrawal using benzos
GABA function plummets and symptoms increase greatly
= rebound anxiety
