Week 7 (Test 3) Flashcards
Glutamate is ___ in nature.
excitatory
GABA is ____ in nature.
inhibitory
regulation of strength of connection between two synapses
synaptic plasticity
Describe glutamate toxicity.
Too much glutamate = excitotoxicity! Excessive Ca2+ intake triggers neuronal injury/death Could stem from: -excessive glutamate release -poor glutamate reuptake Stroke: anoxia can release toxic amounts of glutamate
Benzodiazepines and barbiturates work on which neurotransmitter receptors?
GABA-a receptors
What causes stiff person syndrome?
Antibodies to GAD prevent GABA production, causing autoimmune or paraneoplastic syndrome
How do benzodiazepines work as anti seizure meds?
increases GABA (inhibitory NT) efficiency
How does Valproate work as an anti seizure med?
inhibits enzymes that deactivate GABA
How does Topiramate work as an anti seizure med?
inhibit GABA reuptake
What are the nuclei of origin of dopamine?
substantia nigra (Pars compacta) and ventral tegmental area
How do D1 (dopamine) receptors work?
signal through G proteins to activate adenylate cyclase, causing cAMP formation and activation of PKA
How do D2 (dopamine receptors work?
block D1 signaling by INHIBITING adenylate cyclase, thereby PREVENTING the formation of of cAMP and subsequent activation of PKA
What causes the dopamine deficiencies seen in Parkinson’s?
Death of pars compacta within substantia niagra
What enzyme is involved in the rate limiting step of dopamine formation?
tyrosine hydroxylase
L-DOPA can be given as treatment for Parkinson’s. How does it work?
increase dopamine by Bypassing rate-limiting step in dopamine synthesis and it Easily crosses blood-brain barrier
What is the nuclei of origin of serotonin (5HT)?
raphe nucleus (pons/midbrain)
5HT-1&2 receptor subtypes are involved in _____.
mood, appetite, energy, sexual function
5HT 3 receptor subtype is involved in _____.
nausea (localized in area prostrema)
This medication is used in the treatment of nausea b/c it is a 5HT 3 receptor antagonist.
Ondansentron
Describe what you would see in Serotonin Toxicity (aka Serotonin Syndrome)?
Cognitive: headache, delirium Autonomic: hyperthermia, hypertension Somatic: tremor, hyperreflexia, clonus
What is the nuclei of origin of norepinphrine?
locus ceruleus (pons)
Selective Norepinephrine/Dopamine re-uptake inhibitor
Buproprion (Wellbutrin)
Selective Serotonin/Norepinephrine re-uptake inhibitor
Venlafaxine (Effexor) Duloxetine (Cymbalta)
What is the nuclei of origin of ACh?
Nucleus Basalis of Mynert (inferior to anterior commissure) Pedunculopontine Nucleus (brainstem, caudal to subs. niagra)
What do you see in ACh toxicity (organophosphates/sarin gas)?
SLUDGEM: Salivation Lacrimation Urination Defication Gastrointestinal upset Emesis Miosis (pupil constrict)
What disorders are associated with norepinephrine?
Panic attacks Parkinsonian symptoms
the instinctual fear center
amygdala
the neurotransmitter involved in anxiety
norepinephrine
What’s the drug of choice for general anxiety disorders?
SSRI’s -sertraline, paroxetine, fluoxetine, fluvoxamine, citalopram, escitalopram -They work for Anxiety disorders by reducing Locus Ceruleus (NE synthesis) firing with chronic use
What disorders are very prevalent with anxiety disorders?
alcohol disorders
What does a patient need to have to get a diagnosis of panic disorder?
Recurrent unexpected panic attacks At least one attack has been followed by 1 month or more of: -persistent concern about having more attacks or their consequences (eg. losing control, having an MI, “going crazy”) -significant maladaptive change in behavior related to attacks
What’s the mainstay of panic disorder treatment?
SSRI’s
Marked fear or anxiety about >2 of Using public transportation Being in open spaces (e.g., parking lots, bridges) Being in enclosed spaces (e.g., shops, theatres) Standing in line or being in a crowd Being outside of the home alone
agoraphobia
What do you need to make a diagnosis of generalized anxiety disorder?
Excessive anxiety and worry, more days than not for at least 6 months 3 or more of: restlessness/keyed up/on edge easily fatigued difficulty concentrating/mind going blank irritability muscle tension sleep disturbance
What is the main comorbid disorder seen with generalized anxiety disorder?
major depression
Marked fear or anxiety about >1 social situations in which the person is exposed to possible scrutiny by others Essentially is fear of scrutiny, humiliation or embarrassment
Social Anxiety Disorder (Social Phobia)
What could you give for performance type ( presentations, recitals, etc.) social anxiety disorder ?
beta blockers (can help get rid of the palpitations, racing heart beat, etc.)
What is the most common anxiety disorder?
specific phobia
What’s the best way to treat specific phobias?
Best evidence is for CBT “Systematic desensitization”
What is the most common comorbidity of Tourettes ?
OCD
What’s the pathophysiology of OCD?
Clear orbitofrontal-limbic-basal ganglia circuit abnormality PET and SPECT have found increased metabolism in orbitofrontal and anterior cingulate cortices and caudate nuclei
Because of the pathophysiology of OCD, what are the possible treatments?
Effective tx with either SSRI or behavioral therapy reduces hypermetabolism
Recurrent or persistent thoughts, impulses, or images seen as intrusive or inappropriate that cause marked anxiety/distress
obsessions
Repetitive behaviors or mental acts driven to perform in response to obsession, or according to rules rigidly applied
compulsions
What is the specific cognitive behavioral therapy used to help people with OCD?
Exposure-Response Prevention
Preoccupation with one or more 1 perceived defects or flaws in physical appearance, not observable or slight to others Person has at some point performed repetitive behaviors (e.g., mirror checking, excessive grooming, reassurance seeking) or mental acts in response to concerns
Body dysmorphic disorder
skin picking disorder is also called what?
Excoriation disorder
persistant difficulty discarding or parting with possessions, regardless of their actual value; difficulty is due to perceived need to save the items and to distress associated with discarding them; possessions accumulate and congest living areas
hoarding disorder
Recurrent pulling out of one’s hair, resulting in hair loss Repeated attempts to decrease or stop hair pulling. The hair pulling causes clinically significant distress or impairment in social, occupational, or other important areas of functioning.
Trichotillomania (Hair-Pulling Disorder)
Hair pulling disorder is also called what?
Trichotillomania
What are the two most commonly seen psychiatric comorbidities in PTSD?
depression and alcohol disorders
Symptoms have to be present for what time period before a diagnosis of PTSD can be made?
1 month (less than 1 month would be acute distress disorder)
What changes are often observed in the amygdala, anterior cingulate gyrus, and medial frontal cortex in PTSD patients?
amygdala: hyperactive anterior cingulate gyrus: reduced volume medial frontal cortex: hypoactive
What’s the function of the medial frontal cortex?
Provides “top-down”, frontal lobe control over the amygdala
What is the role of the hippocampus in the normal stress cycle?
Hippocampus is involved in helping to terminate stress responses -Small hippocampi a risk factor for PTSD from twin studies
What’s the simplistic explanation of the physiology of PTSD?
too much NE and not enough cortisol
What are the only FDA approved medications for PTSD?
Sertraline (Zoloft®) in 2001 Paroxetine (Paxil®) in 2002
a short-term evidence-based cognitive-behavioral treatment for PTSD helps the patient identify natural emotions and connect thoughts/feelings predominantly cognitive and may or may not include a written account focused on helping the patient examine their thinking related to the trauma
Cognitive processing therapy
a short-term evidence-based cognitive-behavioral treatment for PTSD predominantly behavioral and may or may not include cognitive restructuring uses imaginal and invivo exposure in addition to relaxation focused on helping the patient habituate to the trauma memory/feelings
prolonged exposure
Name the three major evidence-based psychotherapies for PTSD .
Eye Movement Desensitization Reprocessing , prolonged exposure, cognitive processing therapy
PTSD Treatment Guidelines specifically recommend against ______ use .
long term benzodiazepine use Why? Not effective for core PTSD symptoms Substance abuse and TBI are contraindications for use Tolerance, dependence and withdrawal problematic Interfere with extinction of conditioned fear May reduce efficacy of exposure therapy
What medication should you consider for patients with PTSD who are having sleep/nightmare problems?
Prazosin
What’s the mechanism of action for Prazosin?
Blocks central alpha-1 norepinephrine receptors
What do fMRI’s depend on?
the blood oxygen levels (neuronal activity will result in increased regional blood flow in that area as well as increased regional cerebral blood oxygenation)
90% of PET exams use ____ to measure metabolism.
18Fluoro-2-deoxy-D-glucose (FDG)
Which offers a higher spatial resolution: PET or SPECT?
PET offers higher spatial resolution (“single” photon vs. lots of photons)
Barbiturates, benzodiazepines and “Z-drugs” (and alcohol) all work via _____.
increased GABA-A action via positive allosteric action
What’s the mechanism of action for benzodiazepines?
Increase FREQUENCY of Cl- channel opening
What’s the mechanism of action of barbiturates?
Increase duration of Cl- channel opening
Which benzodiazepines are good for patients with impaired liver function? Why?
(On The Liver) Oxazepam Temazepam Lorazepam They do not require oxidative metabolism.
Why has there been a shift from barbiturates to benzos?
benzos are very mild respiratory depressants especially compared to barbiturates (but if you take benzos with alcohol or opioids you can toss that statement out the window)
What’s the mechanism of action for Flumazenil?
Competitive antagonist for the BenZo binding site on GABA-a
What’s a common use of Flumazenil?
Often used if you aren’t waking up fast enough post surgery
What’s a key side effect of Flumazenil?
Can cause precipitated withdrawal, including seizures, in BZD dependent patients
Which drug classes does Flumazenil block?
Blocks actions of BZDs and Z-drugs –But not for barbiturates, ethanol, opioids, anesthetics–
Barbiturates are ‘absolutely contraindicated’ in patients with what?
patients with acute intermittent porphyria or porphyria variegata –> because barbiturates enhance porphyrin synthesis
What’s the mechanism of action of Buspirone?
5HT1a partial agonist