Anxiety/Depression Class Powerpoint Flashcards
noradrenergic model
-anxiety or depression theory?
- Describe it
- What part of brain is involved?
Anxiety
The premise of this model is that the autonomic nervous system is hypersensitive and overreacts to various
stimuli.
- Peripheral autonomic hyperactivity symptoms that are often associated with anxiety can be explained with this model.
- In situations of perceived threat or fear (or abnormal stimulation), the locus ceruleus (LC), acts as an alarm
center and activates NE release stimulating the parasympathetic and sympathetic nervous systems. - Over time and with chronic central noradrenergic overactivity, a downregulation of alpha-2 adrenoreceptors
occurs and leads to hypersensitivity = panic disorder.
GABA-receptor model
-anxiety or depression theory?
- Describe it
Anxiety
When GABA receptors are stimulated, causes calming
This model of anxiety theorizes that benzodiazepines ameliorate anxiety through potentiation of the
inhibitory activity of GABA
(in essence, they mimic GABA)
seratonin model
-anxiety or depression theory?
- Describe it
Anxiety
Anything that inhibits release of Serotonin will impact the person’s ability to be stable/less anxious
5-HT (aka serotonin) is primarily an inhibitory neurotransmitter that is used by neurons originating in the raphe nuclei of the brain stem and projecting through the brain
- Abnormalities in serotonergic functioning may play a role in
anxiety disorders. - It is postulated that great 5-HT activity reduces norepinephrine activity in the LC, inhibits defense/escape
response and reduces hypothalamic release of CRF. - The SSRIs acutely increase 5-HT levels by blocking the SERT and increasing the amount of 5-HT available
post-synaptically, and are efficacious in blocking the manifestations of panic and anxiety - Buspirone is a 5-HT1A partial agonist which is effective for GAD
**Once serotonin levels are low, this affects all of the other NTs as well. This is true of all NTs, but particularly serotonin
monoamine hypothesis
- What are monoamines?
-anxiety or depression theory?
- Describe it
Depression
Monoamines = compound with single amine group = dopamine, serotonin, NE
Monoamine hypothesis = Not enough serotonin, NE or dopamine being released into the synaptic cleft
(Depletion of these neurotransmitters in the CNS), which causes depression
- Supported by post-mortem studies, antidepressant MOAs and PET scans
neurotrophic hypothesis
-anxiety or depression theory?
- Describe it
Depression (but this mechanisms also shows up in the anxiety section so perhaps both)
Key idea if decreased levels of Brain Derived Neurotropic Factors (BDNF)
Over time with exposure to stress the body releases glucocorticoids. If this happens too often over too long a period of time (or is too acute), the amount of BDNF decreases.
Over time this changes the brain (such as smaller hippocampus)
depression results from decreased neurotrophic support, leading to neuronal atrophy, decreased hippocampal neurogenesis and loss of glia, and that antidepressant treatment blocks or reverses this neurotrophic factor deficit, and thereby reverses the atrophy and cell loss
What kind of drugs work on the Locus Ceruleus and what model that this pertain to?
Drugs that have a specific effect on the LC work for patients with panic disorder:
* Anxiolytics or drugs for panic (e.g. benzodiazepines) inhibit LC firing, decrease NE activity and can also block the effects of anxiogenic drugs (drugs that stimulate the LC).
This relates to the noradrenergic model of anxiety
What does GABA do? As in, what effect occurs when it binds the GABA receptors?
When GABA binds = calming
GABA is the major
inhibitory neurotransmitter in the CNS and has a strong regulatory or inhibitory effect on the 5-HT,
NE, and dopamine systems.
The GABA receptor controls tonic inhibition to reduce neuronal excitability.
When GABA binds to the GABA A receptor, neuronal excitability is reduced
So drugs (like benzos) are basically binding the GABA receptors to induce calming effect
How do benzos interact with GABA receptors?
What model does this pertain to?
- Benzodiazepines bind on the GABA A receptor at the alpha 1, 2, 3 and 5 subunits in combination with
a beta subunit and the ys subunit - The anxiolytic effects of benzos are mediated at the alpha 2 site while sedative effects results from
binding at the alpha 1 subunit.
GABA-receptor model of anxiety
To summarize, an imbalance of what 4 neurotransmitters may predispose a person to anxiety?
GABA
NE
Serotonin
Depoamine
T/F Genetics plays a role in whether a person develops anxiety
True
Why are females more likely to experience anxiety
May be related to:
1) Hormonal factors
2) Less internal locus of control
3) Greater reporting rates
(According to flow chart in Susan’s slides)
In anxiety, an ongoing sense of perceived threat leads to increased cortisol and epinephrine levels. Chronic activation of stress hormones over time causes death of neurons in __________ (what part of the brain?)
Hippocampus
–> the hippocampus shrinks in size!
Decreased neurons in the hippocampus is directly correlated with levels of what substance (hint: it’s the key substance in the neurotrophic hypothesis of depression)
BDNF
= Brain Derived Neurotrophic Factor
What part of the brain regulates the fear response?
(there are many parts of the brain involved in the pathogenesis of anxiety…)
The Amygdala
- maladaptive activation of fear response here leads to increased stress hormones (epi and cortisol)
Technically, in order to diagnose GAD, anxiety needs to persist for what length of time?
6 months
Brief description of how you would characterize GAD
- Unrealistic or excessive anxiety or worry
about a number of events or activities. - The worry is accompanied by physiologic
symptoms.
Brief summary of panic disorder
Begins as a series of unexpected or spontaneous
panic attacks involving an abrupt surge of intense
fear or intense discomfort
- Followed by at least one month of continuous
worry about having another attack. - Accompanied by physiologic and physical
symptoms
Why is it important to consider if a person is elderly when prescribing tx for anxiety/depression?
Decreased liver/kidney fx
Risk of dizziness, other side effects
Non-pharm tx of anxiety
Counselling
Stress management
Mediation, exercise, lifestyle changes
CBT
Sleep hygiene
After initiating an medication for anxiety/depression, how soon until follow up?
Want to see every 2-3 weeks according to Susan until good effect
Major downside/side effect of anxiolytic/hypnotic medications?
CNS depression
Contrast older vs newer sedative-hypnotic drugs in terms of how dose increase affects CNS depresion
Older generation sedative-hypnotics tend to exert linear dose-response slope whereby increases in dose further
than that required for therapeutic effect will further depress CNS function including respiratory and vasomotor
centers with eventual coma and death.
- Newer drugs (and also benzodiazepines) demonstrate a non-linear slope whereby after a certain dose, does not mean more CNS depression
What kinds of drugs are sedative-hypnotics?
Most common = benzos and barbituates
Rate of oral absorption of sedative-hypnotics depends upon _______ (specific characteristic of drug). This also affects the rate at which these drugs enter the CNS
lipophilicity
More lipophilic = faster absorption, more able to get into CNS
Are sedative-hypnotics safe in pregnancy? Breast feeding?
No, all cross the placenta and get into breast milk
Given they are lipophilic, what needs to happen for sedative-hypnotics to be cleared? What special enzymes might be involved in this?
*Clearance of sedative-hypnotics requires metabolism into a more hydrophilic form
(via Phase I and II
biotransformation utilizing CYP450 enzymes).
** Susan emphasized to not forget about CYP450s in lecture
**Will require functioning liver!
MOA of sedative-hypnotics?
The benzodiazepines, barbiturates and other
hypnotics drugs bind to the molecular components of the GABA(A) receptor in
neuronal membranes in the CNS.
causing INHIBITION of GABA (which stops excessive release of stress hormones, etc)
