WEEK 8 - ANXIOLYTICS AND SEDATIVES Flashcards
Anxiety Disorders…Large group of mood disorders including: 6 HN
- Generalised anxiety disorder
2 * Panic disorder
3 * Social anxiety
4 * Obsessive compulsive disorder
5 * Trauma and stressor related disorders
(e.g. PTSD)
6* Phobias (e.g. agoraphobia)
Anxiety Disorders = Generally characterised by recurrent fears or thoughts that are distressing and
interfere with daily life = 4
1 -Panic attacks
2 -Physiological stress responses
3 -Avoidance
- High prevalence and high comorbidity with other mental health disorders (e.g.
Depression)
Neurobiology of Anxiety =
- Variety of ‘neuroendocrine’, ‘neurotransmitters’ and brain connections that may contribute to anxiety disorders
- Symptoms of mood disorders are thought to arise from DISRUPTIONS IN THE BALANCE OF ACTIVITY IN EMOTIONAL PROCESSING CENTRES OF THE BRAIN
Neurobiology of Anxiety -Key areas of the brain implicated = 5
- Prefrontal cortex- Executive functions
- Anterior cingulate cortex- Emotional processing, learning and error detection
3 * Limbic system- Emotional processing and memory
4 – Amygdala 5 – Hippocampus
Neurobiology of Anxiety = 3
HPA
- Hypothalamic pituitary axis (HPA)-
- Neuroendrocrine
negative feedback loop that regulates levels of stress
hormones and response - -Glucocorticoids and mineralocorticoids
Neurobiology of Anxiety =
‘Glucocorticoids are important for a range of cellular processes:’ = 3
-Metabolism,
- stress,
- inflammation, etc
Neurobiology of Anxiety:
Glucocorticoid receptors are expressed in nearly all cell
types in the body and brain = 4
-High expression in
- frontal cortex,
- amygdala and
- hippocampus
Neurobiology of Anxiety -‘Glucocoricoids can modulate neurotransmitter release’
-GABA, dopamine, serotonin and more
Neurobiology of Anxiety = Sex and age differences in stress response
-Males vs females
-Development
Sedatives-
Drugs that DEPRESS the CNS to REDUCE ACTIVITY AND ALERTNESS
Anxiolytics
Drugs that are used to reduce the symptoms of anxiety
Sedatives and Anxiolytics =
Several classes of drugs used that include: 5
- Hypnotics
- Muscle relaxants
- Anti-convulsants
- Benzodiazepines
- Barbituates
what is GABA?
- Major INHIBITORY NEUROTRANSMITTER in the
CNS - Activation of GABA receptors “inhibit”
NEURONS, OBSERVED AS INHIBITORY POST-SYNAPTIC POTENTIALS *** - GABA(A) CHLORIDE INFLUX CAUSES MEMBRANE ‘HYPERPOLARISATION’
- GABA(B) POTASSIUM EFFLUX causes
MEMBRANE ‘HYPER-POLARISATION’
2 TYPES OF GABA receptors?
- ionotropic
GABA (A) - metabotropic
GABA (B)
what is BENZODIAZEPINES…4
- Wide CLINICAL USE
- ENHANCE GABAA RECEPTOR FUNCTION in
the CNS - Prolongs the DECAY OF INHIBITORY POST-SYNAPTIC POTENTIALS]
- Can also INCREASE THE AMPLITUDE OF INHIBITORY POST-SYNAPTIC POTENTIALS IN SOME NEURAL NETWORKS
Benzodiazepines and GABAA Receptors…RELATIONSHIP = 4
- Large heterogeneity in GABA(A) subunit composition
- 7 subunit families (α,β,γ,ε,θ,ρ,δ)
- Most GABAA receptors composed of α,β,γ subunits
- Different combinations of subunits regulates receptor ‘kinetics, affinity for
GABA, etc.’
Benzodiazepines and GABAA Receptors = BINDING SITE RELATIONSHIP
WHAT CAN THEY CAUSE =5
- Benzodiazepines have a BINDING SITE
on GABAA receptors - Depending on the subunit
composition, benzodiazepines can
cause:
- 3. * Sedation
- 4. * Amnesia
- 5. * Anxiolysis
- 6. * Muscle relaxation
- 7. * Protection against seizures
Benzodiazepines and Anxiety = 4
- Tolerance and dose dependence occurs with all benzodiazepines
- Unclear how tolerance develops, but it may be due to a loss in GABAA receptors and/or subunit composition
- If use is stopped abruptly, patients can experience heightened anxiety and several side effects (headaches, tremors, sleep imbalance, etc)
- A gradual decrease in benzodiazepine treatment is recommended to avoid withdrawal and side effects
Benzodiazepines and Dependence = 3
- Patients can become DEPENDENT on
benzodiazepines - Often ABUSED IN COMBINATION WITH ‘OPOIDS’ AND ‘ALCOHOL’
- Can be used ILLICITLY DUE TO ANXIOLYTIC PROPERTIES
WHAT ARE Barbiturates? = 2
- Act on GABAA receptors, INHIBIT GLUTAMATE RELEASE AND NON-NMDA GLUTAMATE RECEPTORS
- POTENT DEPRESSION on CNS DEPRESSION because of its MULTIMODAL ACTION
Anti-epileptic/anti-convulsants = 5
- Traditional anti-epileptic drugs mainly target 3 channels:
- GABA receptors
- Sodium channels
- Calcium channels
- Drugs that target GABA transaminase have anxiolytic effects
WHAT IS ‘SEROTONIN’ (5-HT) = 5
- An excitatory amine neurotransmitter
- Important for mood and eating habits
- Synthesises from 5-hydroxytrptophan
(5-HTP) to make 5-hydroxytrptamine
(5-HT) - Implicated in many mental health disorders
- THE CONCENTRATION OF SEROTONIN IN THE BRAIN IS THOUGHT TO BE DIRECTLY CORRELATED TO LEVELS OF ANXIETY
5-HT Receptors = 3
- 7 subtypes of 5-HT receptors
- All but 5-HT3 (ion channel) are GPCRs
- Expressed pre and post-synaptically
Azapirones = 4
- Act on 5-HT1A receptors (pre and postsynaptically)
- Thought to desensitise pre-synaptic 5-HT1A receptors but down regulate postsynaptic 5-HT1A receptors
- Activation of the GPCR pathways alters adenylyl cyclase and a potassium channel
- May not be effective in severe anxiety States
AZAPIRONES
- BUSPIRONE
- ISPAPIRONE
- GEPIRONE
- RECEPTOR = 5HT(1A)
- TRANSDUCER = Gi
- LOCALISATION
- Hippocampus, septum, amygdala, dorsal raphe, cortex - Agonist
- buspirone, lisuride
Selective Serotonin Re-uptake Inhibitors (SSRIs) =
5
- Fluoxetine is a highly active blocker of the serotonin transporter
- Increases the amount of serotonin at the synapse
- Fluoexetine lacks affinity for neurotransmitter receptors but also acts on other transporters
- SSRIs do not have an immediate therapeutic effect
- Immediate effects of SSRIs are more commonly side effects
5-HT Syndrome
5-HT syndrome is a rare but lethal syndrome where too much 5-HT accumulates in the brain stem and spinal cord
what is XENON GAS = 4
- Xenon is an INERT NOBEL gas
- Typically used as an anaesthetic
- Inhibits excitatory neurotransmission
- Shown to have some efficacy in reducing fear-related behaviour and
memory
Xenon Gas = Sub-anaesthetic xenon gas: 5
1 * Inhibits NMDA receptor (competes for binding site)
2 * Inhibits AMPA receptors
3 * Inhibits nicotinic receptors
4 * Inhibits 5-HT3 receptors
5 * Activates potassium channels
WHAT IS KAVA? = 6
- Common drink in south pacific cultures for tribal and ritualistic purposes
- Contains several bioactive
substances:- Kavain
- Dihydrokavain
- Interacts with GABAA receptors
- Some evidence to suggest inhibition of voltage gated sodium and calcium
channels
