NEURO: Anxiety Flashcards
What is anxiety?
Intermittent anxiety?
It’s a feeling of worry or unease about something with an uncertain outcome.
normal response to certain events
Chronic anxiety
source of anxiety is irrational and causes day to day life problems:
- social disturbances
- incessant worry
- concentration/memory problems
What can be some causes of anxiety?
Past/Childhood Experiences
-e.g. social isolation
Everyday Life & Habits
-e.g. money problems/exams
Diet
-e.g. sugar, caffeine
Physical & Mental Health
-e.g. chronic conditions or depression can trigger/exacerbate anxiety
Drugs & Medication
-e.g. alcohol/recreational drugs (cannabis, cocaine)
Genetics
-only moderate
What are some symptoms of anxiety?
- nervous diarrhoea
- insomnia
- increased heart rate (tachycardia)
- increased respiratory rate
- dizziness
- headaches
- flush red
- sweating
- nausea
- pins and needles
What are the different anxiety disorders?
Classic Anxiety Disorders
- Generalised Anxiety Disorder (GAD)
- Specific phobias (e.g. agoraphobia)
- Social phobias (e.g. selective mutism)
- Panic disorder
Obsessive-compulsive (and related disorders)
- Obsessive-compulsive disorder (OCD)
- Post-traumatic stress disorder (PTSD)
Generalised Anxiety Disorder (GAD)
characterised by an ongoing state of excessive anxiety lacking clear reason or focus
To be diagnosed with GAD…
- Excessive anxiety and worry occur for at least six months, which is difficult to control and impairs the activity of daily living
- Associated with three or more (of six) symptoms
- GAD sufferers’ symptoms are likely to be different from another person’s experience with GAD
Define Specific Phobias
Give some examples of specific phobias.
extreme fears provoked by exposure to a particular situation - often leads to avoidance behaviours
Ø Agoraphobia: fear and avoid places or situations that might cause you to panic and make you feel trapped, helpless or embarrassed
Ø Acrophobia: fear of heights
Ø Ornithophobia: fear of birds
Ø Podophobia: fear of feet
Ø Nomophobia: fear of being detached from your phone
Ø Turophobia: fear of cheese
Ø Triskaidekaphobia: fear of number the 13
Ø Pogonophobia: fear of beards
Social phobias?
Example of social phobias
significant anxiety provoked by exposure to certain types of social (e.g. social gatherings) or performance (e.g. public speaking) situations
Selective mutism
-severe anxiety disorder where a person is unable to speak in certain social situations
Panic disorder
What are panic attacks?
recurring panic attacks, without a seemingly clear trigger
sudden feelings of overwhelming fear marked with somatic symptoms (e.g. sweating, chest pains)
Panic cycle
Individuals experience anxiety about the prospect of having more attacks, and this anxiety can trigger further panic attacks
What is OCD?
Features of OCD
characterised by compulsive, ritualistic behaviour driven by irrational anxiety
- Obsessions: recurrent, intrusive thoughts, images, ideas or impulses (e.g. cleanliness)
- Compulsions: repetitive behaviours or mental acts that are performed to reduce anxiety associated with the obsessions (e.g. washing hands multiple times after shaking hands with someone)
It becomes a problem when it becomes debilitating.
What is PTSD?
distress triggered by the recall of past traumatic experiences- can lead to flashbacks and nightmares
Pathophysiology of anxiety
inappropriate stress response either when a stressor is not present or not immediately threatening
stress response regulated by HPA axis, leading to release of cortisol
Brain regions that regulate HPA axis
amygdala
hippocampus
Role of the amygdala in anxiety
Amygdala- role in emotion and fear response
· Stimulates HPA axis to promote cortisol release
· Amygdala hyperactivity linked to anxiety disorders
Role of the hippocampus in anxiety
Hippocampus- role in learning and memory
· Suppresses HPA axis to prevent excessive cortisol release
· Hippocampus underactivity linked to anxiety disorders
Effect of increased cortisol on the hippocampus
continuing exposure to cortisol (e.g. during periods of chronic stress) can cause neuronal degeneration in the hippocampus
this sets off a vicious cycle in which the stress response becomes more pronounced, leading to greater cortisol release and more hippocampal damage.
Neurotransmitter imbalance in anxiety
imbalance between inhibitory GABA and excitatory glutamate neurotransmission
-less GABA neurotransmission
Anxiolytic Drugs (What are some treatments for anxiety?)
GABAa Receptor Modulators
Ø Barbiturates
Ø Benzodiazepines
5-HT1A Receptor Agonists
β-Adrenoceptor Antagonists
Describe benzodiazepines.
Where do benzodiazepines bind?
class of GABAa modulators which stabilise the GABAa receptor binding site for GABA in open configuration- increases GABA affinity for its binding site and produces a general enhancement of its neuroinhibitory actions -increasing inhibitory neurotransmission, can relieve some of the symptoms an anxiety sufferer exhibits
between the alpha and gamma subunits of the chloride ion channel (enhances ability of GABA to keep ion channel open)
What kind of compounds are benzodiazepines considered as? and why?
Benzodiazepines are “cleaner” compounds to the barbiturates, meaning they are much more specific for the GABAa receptor compared to the barbiturates that act at various different receptors.
How do we choose which benzodiazepine to use?
What are benzodiazepines and barbiturates associated with?
duration of action (e.g. short-acting preferred as hypnotics to avoid sedation throughout the day)
tolerance and withdrawal symptoms
What are Barbiturates (no longer recommended as anxiolytics)?
Effect of barbiturates on CNS
class of GABAa positive allosteric modulators -increase the activity of GABAa receptors, binding increases channel opening beyond that seen with GABA alone, more Cl- influx
responsible for a severe depressant effect on CNS
What kind of compounds are barbiturates considered as? and why?
Considered “dirty” compounds, meaning they can act on various other receptors in addition to the GABAa receptor to cause an increase in inhibition and a decrease in excitation.
Ø Glycine receptor- also stabilises the open channel
Ø nAChR & 5-HT3 receptor blockade
Ø AMPA/Kainate receptor blockade
Ø Blockade of Ca2+ channel-dependent neurotransmitter release
What can barbiturates be used for?
Where do barbiturates bind?
- Epilepsy
- General Anaesthesia
- Capital punishment (e.g. phenobarbital)
between beta and gamma subunits of the chloride ion channel
5-HT1A receptor agonists
Structure of 5-HT1A receptor
Buspirone
- class of drugs used to treat anxiety
- less tolerance and withdrawal symptoms compared to the benzodiazepines
GPCR (Gi/o) to inhibit adenylate cyclase
- autoinhibitory
- decreases 5-HT release
What is buspirone most commonly prescribed for?
generalised anxiety disorder (GAD)
>activates pre-synaptic 5-HT1A autoreceptors, inhibiting 5-HT release
>also reduces activity of noradrenergic neurones and decreases arousal (but does not induce sleep)
Benzodiazepines, barbiturates and addiction
Symptomatic
· Imbalance between inhibitory GABAA and excitatory glutamate in patients suffering from a number of anxiety disorders- GABA neurotransmitter levels are often low
Barbiturates + Benzodiazepines
·Patient prescribed benzodiazepines which act as positive allosteric modulators to stabilise the GABAA receptor binding site for GABA in the open configuration
· This increases GABA affinity for its binding sites and produces a general enhancement of GABA’s neuroinhibitory actions, which can suppress symptoms of anxiety in some patients
Tolerance
· Over time, a patient can develop tolerance to benzodiazepines due to the trafficking of additional glutamate receptors to the cell membrane, which serve to restore the initial imbalance seen in the “symptomatic” stage/increase excitatory neurotransmission.
· Patients therefore need to take higher doses of benzodiazepines to address this new imbalance between inhibitory and excitatory neurotransmission
Withdrawal
· If patient suddenly withdraws from taking these high doses of benzodiazepines, there is a sudden decrease in inhibitory GABA neurotransmission.
· Coupled with increased excitatory glutamate neurotransmission, this can lead to the development of seizures.
What are the cons of increasing of 5HT transmission?
What are the cons of decreased 5HT transmission?
- you get fewer 5HT(1A) receptors
- 5HT reuptake is inhibited
- you get fewer postsynaptic 5HT receptors
What are the cons of decreased 5HT transmission?
- you get fewer postsynaptic 5HT receptors
Activity of buspirone
· 5-HT1A receptors are autoinhibitory and, therefore, buspirone initially inhibits 5-HT release.
· However, if buspirone is taken over a period of time (e.g. weeks), buspirone can induce desensitisation of autoinhibitory 5-HT1A receptors.
· This desensitisation can lead to downregulation of 5-HT1A receptors on the pre-synaptic plasma membrane.
· The desensitisation and downregulation of 5-HT1A receptors ultimately results in heightened excitations of serotonergic neurones and enhanced 5-HT release, which can suppress symptoms of anxiety shown in patients.
The activity of SSRIs in anxiety (not 5HT1A agonists)
Inhibits the reuptake of 5-HT via SERT:
· This leads to an increase in 5-HT availability at the synaptic cleft.
· If SSRIs are taken over a period of time (e.g. weeks), SSRIs can induce desensitisation of autoinhibitory 5-HT1A receptors.
· This desensitisation can lead to the downregulation of 5-HT1A receptors on the presynaptic plasma membrane.
· However, in addition, SSRIs can also lead to the downregulation of 5-HT receptors on the post-synaptic plasma membrane.
· Overall, there is an increase in 5-HT neurotransmission (via fewer autoinhibitory 5-HT1A receptors and inhibiting the reuptake of 5-HT) and a decrease in 5-HT neurotransmission (via fewer post-synaptic 5-HT receptors). On the balance of these changes, there is an overall increase in 5-HT neurotransmission, which can suppress the symptoms of anxiety in some patients.
Structure of β adrenoceptor
Describe how adrenoreceptors can be used to combat anxiety.
β-adrenoceptor antagonists
GPCRs (Gs) to activate adenylate cyclase
Adrenoreceptors are used to reduce peripheral symptoms of anxiety, such as tachycardia and increased blood pressure. They act on β1 and β2.
For these reasons, taking them can be considered as drug doping in precision sports.
Propranolol -class of drugs used to treat peripheral symptoms of anxiety (e.g. tremor, sweating, tachycardia, diarrhoea)
Describe how anti-histamines can be used to combat anxiety.
You take them to down-regulate inflammatory responses.
They have a hypnotic/ sedative effect. To avoid that, there are versions that don’t cross the blood-brain barrier to only treat the peripheral symptoms.
