PBL 7 - Anxiety Flashcards
What determines whether an input leads to an action potential?
AP depends on the summation of synaptic inputs on the postsynaptic neuron
What is the main excitatory neurotransmitter?
What receptors does it work on?
How does it work?
Glutamate
• causes influx of Na or Ca leading to depolarisation
• More than half of all brain synapses release glutamate
• Starts AP and also keeps them going
• NMDA or AMPA
What is the main inhibitory neurotransmitter?
What receptors does it work on?
How does it work?
GABA • Causes Cl influx and K efflux • Leads to hyperpolaration • 30-40% of all synapses release GABA • Stops or prevents AP • GABA receptors
What are the two main neurotransmitter receptor types?
How do they differ?
What kind of NT act on each?
Ionotropic receptor • Ligand gated ion channel • Not a transporter • Has a direct action • Action is rapid and brief
Metabotropic receptor • GPCR • Indirect action • Takes longer to work • Catecholamine and peptide NT work on these only
NOTE:
Most NT can act on both
What are some examples of Ionotropic receptors?
• Excitatory ○ Ach gated cation channels ○ Glutamate gated ca channels ○ Serotonin cation • Inhibitory ○ Gaba-a gated CL channels ○ Glycine gated CL channels
What type of receptors are GABA-A?
What are the characteristics?
How do they work?
What stimulates and inhibits them?
- Ionotropic
- Causes CL influx
- Inhibitory effect on the AP
Structure:
• 5 sub-units
• Has a benzo and a barbitruate binding site
• Potentiated by neurosteroids, benzos, barbitruates and alcohol
Inhibited by toxins - picrotoxin and convulsants
How do Barbitruates work on the GABA receptor?
- Does not need GABA present to work
* Increases channel opening DURATION
How do Benzodiazepines work on the GABA receptor?
- It is a modulator
- Has no intrinsic activity
- Needs GABA to work
- Increase channel opening FREQUENCY
- Increases affinity of GABA for receptor by slowing GABA unbinding from receptor
- Number of receptor occupancy determines effects
What type of receptor is a Neuronal ACH R
What is the structure?
What effect does it have
- Ligand gated ion channel- ionotropic
- Many different combinations of a pentamer
- Allows calcium to come in
- Excitatory effect
- Alterations are found in many diseases for example alzheimers disease
What kind of receptor is a Glutamate ?
What are they implicated in?
What works on them?
- It is an excitatory ionotroic receptor
- There are 3 functional classes○ NMDA
§ Has binding sites for glutamate, mg, glycine and others
§ At resting membrane state the channel is blocked by magnesium
§ When the cell is depolarised the Mg is removed to allow Na and Ca can flow in, often K efflux○ AMPA
§ Glutamate opens AMPA channel allowing Na influx
§ This depolarises the membrane and removes the Mg from the NMDA channel which must have glutamate bound aswell○ Kainate
• They are modulated by many substances
○ Alcohol
○ PCP: NMDA antagonists - There are 3 functional classes○ NMDA
What causes Glutamate toxicity?
What are the consequences?
Glutamate toxicity
• Due to excess glutamate ○ Either through excessive release and or decreased reuptake by neuronal or glial cells • Causes sustained stimulation of postsynaptic glutamate receptors- mainly NMDA • Causes increased Ca influx leading to intracellular Ca overload • Increased oxidative and metabolic stress • Cell death
How fast are effects of GCPR mediated signalling?
- Can induce both slow initial synaptic potentials and long term effects
- Can open ion channels
- Also enzymes, structural proteins and gene transcription
How to metabotropic receptors work?
- There is an indirect action of the NT on the ion channel
- Binding activates a G protein which causes activation of a second messenger that creates a cascade to eventually open the ion channels
- Sometimes the Channel has a g-protein that directly opens the ion channel
Do NT only work on one type of receptor?
What is an example?
- Not usually
- It is possible for one NT to activate different classes of receptors
- Ie there is an iGLUr and a mGLUR that glutamate can act on
What will determine the effect of the NT on the receptor?
What is an example?
- One class of receptor can have many subtypes which will effect the response
- Each subtype can have broad or restricted tissue/cell distribution
- Example the type of GCPR and the G protein will determine the effect of the NT
Is the action of the NT signalling pathway linear? Why?
- NO the same NT can activate a variety of effectors through activation of signalling pathways
- There is signal amplification and signal DIVERGENCE
- Signals from unrelated receptors may converge to activate a comon target ex- memory formation- stress pathway assists with memory by activating the same pathway
- There is cross talk between different distinct NT activated pathways
How are long term adaptive changes made?
How does this relate to alcohol?
• Occur through changes in gene expression
• Can alter receptor density or receptor sensitivity to neurotransmitter or drug
• Example will try to compensate with chronic alcohol use
○ Upregulation of mGLUR- homer to increase glutamate release in the situation where alchol is suppressing transmission
○ Withdrawal occur when this compensation has occurred and then the suppression from alcohol is not present any more- only increased stimulation occurs
What Ions does the glutamate NMDA receptor let though?
What causes the channel to open?
- Na in
- K out
- Ca in
- It is voltage as well as chemically dependent
- Usually blocked by a mg ion. Depolarisation causes the Mg to leave the channel then it conducts
What ions does the glutamate AMPA receptor let through?
- Na in
* K out
What is anxiety?
• Experienced in response to a perceived threat
○ Fear: imminent threat, fight/flight response
○ Anxious arousal: distant or poorly defined threat, hypervigilance and unease
• Normal part of life
When does anxiety become a disorder?
Anxiety becomes a disorder when:
• It is excessive and unreasonable in the circumstances
• Is persistent
• Is distressing
• Interferes with functioning (social, work or home)
• Most people are aware that this is unreasonable- usually after they are out of the situation
What is the most common mental health issue in Australia?
• Anxiety
What comorbidity worsens the prognosis of depression?
• Comorbid anxiety
What is the epidemiology of anxiety?
Onset and demographic
- Onset in teens to thirties most common
* Generally female
What are the risk factors for anxiety?
• Temperament/personality
• Environment:
○ Childhood adversity
○ Conditions of significant uncertainty/threat
What are the symptoms of anxiety?
Physical: • Increased HR • Dry mouth • Sweating • Tremor • Flusing • Tnesion • Urge to urinate/defaecate • Diziness • Globus hystericus • SOB • Numbness and tingling • Derealisation • Depersonalisation
Cognitive/emotional • Fear • Anxious arousal • Worry • Sense of impending doom
Behavioural
• Avoidance
• Reassurance seeking
Safety behaviour
What is hyperventilation and how is it treated?
- Breathing techniques and targeting catastrophic beliefs about consequences of anxiety
- Some people are more sensitive to CO2 and they are more susceptible to panic attacks
- Not everyone with anxiety have abnormal co2 sensitivity
- Not linked to other anxiety disorders
What is considered as an Anxiety disorder?
- Panic disorder
- Agoraphobia
- Social anxiety disorder
- Specific phobias
- Separation anxiety disorder
- Selective mutism
How are anxiety disorders differentiated?
Anxiety disorders are differentiated by the form that the anxiety takes: • Intrusive thoughts/images • Compulsions • Worry • Panic
Feared consequences are important and the content of the fear can assist
GAD = bad or catastrophic outcome
Panic/agoraphobia = losing control, death, physical disorder
Separation anxiety = attachment figure coming to harm
Selective mutism = fear of speaking
What is the main source of disability in Anxiety?
• Avoidance
What is the most effective treatment of avoidance?
exposure therapy
What is the treatment approach for anxiety?
• Education about anxiety • Interbased CBT • Face to face CBT • Pharmacotherapy • Lifestyle ○ Exercise ○ Decrease stimulants ○ Decrease alcohol ○ Stress management ○ relaxation
Is there evidence for Beta blockers in anxiety?
• Evidence shows that it is not better than placebo
What is the first line treatment for anxiety?
- CBT
- SSRI in all anxiety disorders
- SNRIs specifically in GAD, Panic/agoraphobia and social anxiety
How long Does it take for antidepressants to work in anxiety? How does this compare to depression?
How long should they be taken for?
- takes 6 weeks or more
- Longer than depression
- Should be taken for at least 6 months
- No evidence of dose-response relationship except for OCD
What does a Depressant do?
What are some examples?
• Act upon the brain and CNS to slow it down • DRUGS: ○ Alcohol ○ Opiates (Heroin) ○ Benzodiazepines ○ Cannabis • Overdose causes: ○ Heart failure ○ Respiratory failure ○ death
What does the DSM 5 say about alcohol use disorder?
A problematic pattern of alcohol use leading to clinically significant impariement or distress as manifested by at least two of the following occuring within a 12 month period
1. Alcohol is often taken in larger amount or over a longer period of time than was intended 2. There is a persistent desire or unsucessful efforst to cut down or control alcohol use 3. A great deal of time is spent in activities necessary to obtain alcohol, use alcohol or recover from its effects 4. Craving or a strong desire or urge to use alcohol 5. Recurrent alcohol use resulting in a failure to fulfil major role obligations at school, work or home 6. Continued alcohol use despite having persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of alcohol. 7. Important social, occupational, or recreational activities are given up or reduced because of alcohol use. 8. Recurrent alcohol use in situations in which it is physically hazardous. 9. Alcohol use is continued despite knowledge of having a persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by alcohol 10. Tolerance, as defined by either of the following: a. A need for markedly increased amounts of alcohol to achieve intoxication or desired effect. b. A markedly diminished effect with continued use of the same amount of alcohol. 11. Withdrawal, as manifested by either of the following: a. The characteristic withdrawal syndrome for alcohol (refer to criteria set for alcohol withdrawal). b. Alcohol (or closely related substance such as benzodiazepine) is taken to relieve or avoid withdrawal symptoms.
What are the signs of alcohol withdrawal?
• autonomic hyperactivity (sweating or pulse rate greater than 100 bpm • Increased hand tremor • Insomnia • Nausea or vomiting • Transient visual, tactile or auditory hallucinations or illusions • Psychomotor agitation • Anxiety Generalised tonic clonic seizures
What are Hallucinogens?
What are some examples?
Hallucinogens are a category of drugs that have in common the ability to cause subjective changes in perception, thought, emotion and consciousness
DRUGS: • Phencyclidine (PCP, angel dust) • Ketamine (special K) • Cyclohexamine (PCE, Rocket fuel) • Dizocilpine
What are stimulants?
What are some examples?
timulants are a group of drugs that speed up the CNS
• people using these can develop a stimulant use disorder in a week
DRUGS: • Amphetamine • Dextroamphetamine (dexies) • Methamphetamine (Speed, meth, ice, crystal) • Cocaine (coke)
What are the stages of change?
Stages of change
• Precontemplation ○ Not ready to change ○ Validate lack of readiness ○ Encourage re-evaluation of current behaviour and self exploration ○ Explain and personalise the risk
• Contemplation ○ Thinking of changing ○ Encourage evaluation of pros and cons of behaviour change ○ Identify and promote new positive outcome expectations • Preparation ○ Ready to change ○ Encourage to evaluate pros and cons of behaviour change ○ Promote new and positive outcome expectations ○ Small initial steps • Action ○ Making change ○ Help the individual on restructuring cues and social support ○ Enhance self efficacy for dealing with obstacles ○ Help to guard against feelings of loss and frustration
• Maintanance ○ Staying on track ○ Plan for follow up support ○ Reinforce internal rewards ○ Discuss coping with relapse
• Relapse ○ Help identify trigger for relapse ○ Reassess motivation and barriers ○ Plan stronger coping strategies
What are the risk factors for dependence?
- Age of first use
- Low socioeconomic status
- Familial history/Genetic tolerance
- Support systems (family, school, church)
- Peers
- Pscyhological health/comorbidity
- Timing of a significant life event
