Exam 4 Material Flashcards
Fear is divided into ____ fear and ____ fear.
innate; learned
What coordinates the global response to a perceived threat?
the amygdala
Sensory input to ___ ____ activates numerous effector sites for physiological and behavioral fear response.
central nucleus
What are the 8 physical responses of the amygdala?
sympathetic activation (tachycardia, bp increase, etc); urination/defecation; increased vigilance/attention; increased startle; hypoalgesia; fear facial expression; corticosteroid release
Can patients with damage to the amygdala still feel fear?
yes- inhaling CO2 can produce a fear response
What neurotransmitter plays a critical role in the circuitry mediating anxiety?
corticotrophin-releasing factor (CRF)
What two components make up a memory of a fearful situation and what brain area processes those?
1- cognitive processed in hippocampus
2- affective processed in teh mygdala
What type of memory component is the precise setting or context in which the danger is experienced?
the cognitive
What type of memory is of emotional salience?
the affective
In anxiety there is no what?
immediately threatening situation
Anxiety is what kind of association with memory?
maladaptive
This is characterized by discrete episodes of intense anxiety with somatic symptoms such as tachycardia, tachypnea, and dizziness.
Panic disorder
this is an unrealistic excessive worry for more than six months with symptoms such as motor tension, sympathetic hyperactivity, and excessive vigilance.
Generalized anxiety disorder
This happens after serious trauma and is associated with cue-eliceted reliving of traumatic experience, increased startle, and nightmares.
Post-traumatic stress disorder
This is fear of social situations or interactions.
social phobia
How do you treat acute anxiety?
benzodiazepines
How do you treat GAD?
antidepressants or benzos
How do you treat panic disorder?
long term anti-depressants and behavioral therapy
How do you treat OCD?
long term anti-depressants and behavioral therapy
How do you treat PTSD?
behavioral therapy, cycloserine, ketamine, prazosin, propranolol
How does cycloserine work?
it’s an NMDA agonist
How does parzosin work?
it’s an alpha1 antagonist
What is a common ending to generic names for benzos?
-azepam
What are the five types of anti-anxiety medications?
1- benzos 2- barbiturates 3- beta adrenergic receptor antagonists 4- newer such as CRF and neuropeptide antagonists 5- 5HT 1A recepor agonists
Name four examples of benzos?
diazepam, chlordiazepoxide, oxazepam, clorazepate, alprazolam, prazepam, halazepam, lorazepam
What receptor do barbiturates work on?
GABA-A
What are additional therpeutic uses for benzos beyond anxiety?
muscle spasticity seen in MS and cerebral palsy, seizures, and sleep disorders
Which benzo treats anxiety?
diazepam
Which benzo treats muscle spasticity?
diazepam
What three benzos can treat seizures?
clonazepam, diazepam, oxazepam
Which benzos can treat sleep disorders?
flurazepam, temazepam, triazolam
What are the drawbacks to using benzos?
they can impair intellectual functions, interact with alcohol, and cause withdrawal if stopped suddenly
Which benzos have the longest half life?
diazepam, cholrdiazepoxide, prazepam, clorazepate
Which benzos have shortest have life?
lorazepam, oxazepam and flurazepam
How do benzos that are agonists at the recptor behave?
they reduce anxiety, muscle tension, convulsions, vigilance and memory
How do benzos that are inverse agonists at the receptor behave?
they induce anxiety and oppose agonists; only used with research and not used in humans
How does flumazenil behave at the receptor?
it prevents both types of agonists and blocks access to BDZ receptor
Name the three subunit-selective drugs at alpha-1 receptors?
zolpidem, zaleplon, eszopiclone
What function do alpha-1 selective drugs perform?
they are typically used as sleep aids
Which alpha-1 selective drug has the longest halflife?
eszopiclone (aka lunesta)
How do barbiturates work on the receptor?
they bind to a different allosteric site than benzos on GABA A receptors and directly activate it
What are the drawbacks to using barbiturates?
they creat tolerance, physical dependence, liver issues, and can have withdrawal symptoms
What are barbiturates typically used for?
anasthesia
How do SSRIs work?
they block 5-ht reuptake transporter
How do SNRIs work?
they block 5-ht and NE reuptake transporters
What are some drawbacks to SNRIs and SSRIs?
they can potentially worsen anxiety for a short time, have side effects including: nausea, diarrhea, decreased sex drive,, anorgasmia, and weight gain
SSRIs with a ___ half- life are more likely to cause SSRI discontinuation syndrome.
short
How does buspirone act at the receptor?
it is a 5-HT1a receptor agonist
Does buspar cause sedation?
no
How long does it take for buspar to work?
at least a week
How effective is buspar when compared to benzos or SSRIs?
it is not as effective
What is vilazodone?
it’s a combination of SSRI and buspar
How do beta blockers work at the receptor?
they are beta adrenergic antagonists
What effect do beta blockers have on NTs?
they reduce the effects of catecholamines
What effect on symptoms do beta blockers have?
they reduce anxiety induced heart palpitations, tremor, sweating
What types of anxiety is propranolol good to treat?
performance anxiety and PTSD
Where are D1 receptors found?
neostriatum, cerebral cortex, olfactory tubercle and nucleus accumbens
Where are D2 receptors found?
neostriatum, olfactory tubercle and nucleus accumbens
Where are D3 receptors found?
nucleus accumbens and islands of calleja
Where are D4 receptors found?
midbrain and amygdala
Where are D5 receptors found?
hippocampus and hypothalamus
most antipsychotic drugs block ___ receptors wheras apriprazole is a _____ ____.
D2, partial agonist
What are the reward pathways that are activated?
nucleus accumbens and VTA
Output neurons from the NAc are…?
GABAergic
Rewarding inputs _____ the activity of GABAergic NAc neurons.
inhibit
___ or ____ receptors on NAc neurons are inhibitory.
Opioid, DA
Opioids ___ NAc neurons directly but also ____ GABAergic VTA interneurons.
inhibit x2
Nicotine activates _____ and ___ VTA neurons.
opioidergic; DA
What do cannabinoid do to glutaminergic input into the NAc?
they inhibit it
What six thing increase dopamine in the NAc?
1- heroin and cocaine 2- nicotine 3- alcohol intake 4- THC 5- food 6- caffeine
What causes tolerance to dopamine in the NAc?
compensatory regulation
What five types of tolerance are there?
1- PD tolerance 2- PK tolerance 3- behavioral tolerance 4- cross tolerance 5- reverse tolerance
What is reverse tolerance also known as?
sensitization
This is a physiologic tolerance to others of same drug class or similar action.
cross tolerance
This is adjustment of behavior to compensate for adverse effects.
behavioral tolerance
This is increased metabolism due to enzyme reduction.
pharmacokinetic tolerance (PK tolerance)
This is compensatory change of receptor number or sensitivity.
pharmcodynamic tolerance (PD tolerance)
Acute cocaine increases dopamine binding to what two receptors?
D1 and D2
What happens to compensate for chronic cocaine use?
reduction of Gi and increase of anaylate cyclate (leading to more cAMP and sensitization)
Define addiction.
habitual dependence on a substance or practice beyond voluntary control
What is the impact of chronic drug use?
normal reward function is replaced and it leads to craving/loss of control/addiction
What is one potential cause of aura in migraine?
cortical spreading depression
What is cortical spreading depression?
waves of electrical excitability followed by depression that moves across the cortex at approximately 3-6 mm/min
Meningeal afferents are sensitive to what types of things?
chemical (low pH, inflammatory mediators) and mechanosensitivity
What explains the throbbing pain?
mechanosensitivity
What are abortive therapies for migraines?
nsaids, ergots, triptans, CGRP antagonists
slide 19 migraines
start with ergot questions
