Anxiety disorders and agents used to treat them Flashcards
What regions of the brain does most research point to as being involved with anxiety?
prefrontal cortex, amygdala, hippocampus, and HPA axis
Kulver Bucy Syndrome
Role of temporal structures on emotions and temperament, but especially the amygdala (monkeys that had removed temporal lobe segments made them docile and unable to learn from negative experience)
The removal of just the amygdala is enough to
cause Kluver-Bucy Syndrome
What is the amygdala responsible for?
recognition and management of fear
How do we recognize danger
Thalamus projects auditory and visual information to the amygdala that is perceived as threatening BEFORE sending it to the cortex to be processed.
Where is brain activity during anticipatory anxiety?
Activity in the amygdala, hippocampus, and insula
What memory changes occur due to fear?
Structural changes in the amygdala in reaction to fearful circumstances
Feelings of fear are regulated by an OVERACTIVE reciprocal connections between
the amygdala and the anterior cingulate cortex and the amygdala and the orbitofrontal cortex
One of the central components of anxiety is the feeling
that one is not in control
What is the metaphorical brakes for the amygdala?
the mPFC (medial prefrontal cortex)
Patients with PTSD have demonstrated that their pre frontal cortex is
insufficiently powered and unable to turn down the “alarm” in the amygdala
What interaction between nature and nurture can be considered responsible for the development of PTSD?
A small hippocampus and exposure to trauma
Which neurotransmitters have been implicated in the anxiety response?
GABA, NE, BDNF
Activating GABA neurons
calms the brain down
Too much GABA activation causes
sluggishness and even coma
Stressed rates show increases in
NE release
Peripheral NE causes
somatic symptoms of anxiety
What is essential for the acquisition and extinction of anxiety?
BDNF
What is the relationship of breastfeeding and anxiety?
A recent study saw that children whose parents separated or divorced when the children were between the age of 5 and 10 were more resilient and less anxious if they had been breastfed.
What specific part of the brain is affected in OCD?
Basal Ganglia
Serotonin is the key neurotransmitter in
the amygdala and in elements of the CSTC circuits
Which medication is a general anxiolytic but not approved for anxiety disorder subtypes?
Buspar
What types of antidepressants are effective in reducing symptoms of anxiety and fear?
Antidepressants that increase serotonin SSRIs and SNRIs
Which neurotransmitter subtype is the target of benzodiazepines?
GABA-A receptors
A GABA A subunit alpha 1 when activated induce
sedative and amnestic effects
A GABA-A subunit alpha 2 when activated induce
anxiolytic effects
The only GABA A receptors that are sensitive to benzodiazepines are those with
benzodiazepine isoform known as benzodiazepine-sensitive GABA A receptors
How do benzodiazepine theoretically treat anxiety?
By reducing the amygdala output and enhancing the actions of inhibitory interneurons in CSTC circuits
All beneficial effects and most adverse effects result from what benzodiazepine function?
Depression of the CNS
How do benzodiazepines affect the limbic system?
reduce anxiety
How do benzodiazepines affect the cortical areas?
they promote sleep
How do benzodiazepines affect the supraspinal motor areas including the cerebellum?
muscle relaxation
How do benzodiazepines affect the hippocampus and cerebral cortex?
retrograde amnesia and confusion
What is the cardiovascular effects of benzodiazepines when taken orally? when taken IV?
Orally almost no effect. IV profound hypotension and cardiac arrest
In patients with normal respiratory function benzodiazepines cause respiratory issues when combined with
other CNS depressants
In patients with liver disease what are the preferred benzodiazepines?
oxazepam, temazepam, and lorazepam
What half life caution is important to know with benzodiazepines?
Some of those medications have a short half life but are converted into active metabolites with an extremely long half life
For a patient who needs help falling asleep what type of benzodiazepine would you prescribe?
one with a rapid onset like triazolam
For a patient who needs something because they wake up later in the night what type of benzodiazepine would you prescribe?
one with a slower onset estazolam
For a patient who is older what benzodiazepine is preferred?
one which is unlikely to accumulate with repeated dosing such as lorazepam
What are the major adverse effects of benzodiazepines?
CNS depression, anterograde amnesia, sleep driving, paradoxical effects, respiratory depression, abuse (lower potential), use in pregnancy/lactation (category D and X)
Death from overdose with oral benzodiazepines alone
has never been documented
What should NEVER be taken with benzodiazepines?
other CNS depressants
Discontinuation of a benzodiazepine?
Can cause withdrawal. Good practice includes tapering over weeks and/or months, replacing a long half life with a short half life. Monitor patients for three weeks after cessation for recurrence or withdrawal.
What are the indications of an oral benzodiazepine overdose?
drowsiness, lethargy, confusion
What are the indications of IV toxicity of benzodiazepines?
life threatening reactions, profound hypotension, respiratory arrest, and cardiac arrest
What would the general treatment measures for an oral overdose of benzodiazepines?
gastric lavage, activated charcoal, saline cathartic, and dialysis
What reversal agent is used for benzodiazepines?
Flumazenil
For patients who do not respond to SSRIs/SNRIs or benzodiazepines what is great option either singly or in combination with these other medications?
Alpha 2 delta ligands (Gabapentin/Neurontin and Pregabalin/Lyrica)
Which medication category is used for GAD but not specific anxiety disorders?
benzodiazepines
Which medications are utilized for all anxiety disorders?
SSRIs
What is a useful way to incorporate benzodiazepines into treatment of those with GAD?
When initiating SSRI/SNRI since they have a delayed onset, top up an SSRI/SNRI with those with only partial relief, and intermittent use when symptoms surge and sudden relief is needed
What are the first line treatments for Panic disorder?
SSRIs, SNRIs, buspirone, alpha 2 delta ligands
What are the second line treatments for Panic disorder?
benzodiazepines and tricyclic antidepressants
How many tablets do you give for rescue benzodiazepines?
only 3-5 tablets
What is the first line treatment for social anxiety disorder?
First line SSRIs, SNRIs, and alpha 2 delta ligands
What can be used for performance anxiety?
beta blockers
What is the first line treatment with post traumatic stress disorder?
SSRIs and SNRIs
What can be used to treat PTSD nightmares?
alpha 1 antagonist at night
