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
What is Buspirone approved for treating?
Only approved for Generalized Anxiety Disorder
What’s the mechanism of action of Ramelteon?
Agonist at MT1 and MT2 melatonin receptors located in the suprachiasmatic nuclei of the brain —MT1 receptor agonists promote the onset of sleep, MT2 receptor agonists shifts timing of the circadian system
What is Ramelteon used to treat?
only used for insomnia
What’s the clinical relevance of the Habenular nuclei?
STIMULATE LATERAL HABENULA = Hopeful TREATMENT for DEPRESSION that DOESN’T RESPOND TO MEDS
Light turns the pineal gland ____.
off
When the pineal gland is turned on (in the dark), what does it do?
produces and releases MELATONIN into blood Functions in: Antigonadotropic - Sex Cycles Sleep/Wake Cycle – Feel Rested
Increased melatonin will lead to what?
HYPOgonadism
Decreased melatonin will lead to what?
Precocious Puberty
In burst firing by thalamic neurons, Calcium channels are ___.
active
In tonic firing by thalamic neurons, calcium channels are ____.
inactivate
Burst firing by thalamic neurons will lead to what?
sending NO Details; solely Aware of Event (NO Details, also Sleep)
Tonic firing by thalamic neurons will lead to what?
sending Detailed information, Focusing
Where do thalamocortical fibers run?
in the internal capsule
What’s the blood supply of the thalamus?
posterior cerebral artery
What makes up the epithalamus?
Habenular Nucleus AND Pineal Gland
Which thalamic nuclei are labeled as “diffuse type”?
Centro Medial
Which thalamic nuclei are labeled as “external relay type”?
Ventro Posterior Lateral Ventro Posterior Medial Lateral Geniculate Medial Geniculate
Which thalamic nuclei are labeled as “internal relay type”?
Ventro Anterior Ventro Lateral Anterior
which thalamic nuclei are labeled as “association type”?
Dorso Medial
Describe afferent and efferent pathways involved in the Ventro Posterior lateral nuclei.
IN from Dorsal column medial lemniscus + Spinothalamics OUT to Somatosensory Cortex (body)
Describe afferent and efferent pathways involved in the Ventro posterior Medial nuclei.
IN from Trigeminothalamics, CTT (taste) OUT to Somatosens. Cortex (face), Insula (taste)
Describe afferent and efferent pathways involved in the Lateral Geniculate nuclei.
IN from Retina (via optic tract) OUT to Calcarine Cortex (via geniculocalcarine tract)
Describe afferent and efferent pathways involved in the Medial Geniculate nuclei.
IN from Inferior Colliculus (via brachium of inferior colliculus) OUT to Auditory Cortex (via auditory radiations)
Describe afferent and efferent pathways involved in the Anterior Nuclei.
INPUT from Mammillary Bodies (mammillothalamic tract) OUTPUT to Cingulate Gyrus
Describe afferent and efferent pathways involved in the Ventro Anterior nuclei.
INPUT from Basal Ganglia OUTPUT to Motor (4) and Premotor (6) Cortex
Describe afferent and efferent pathways involved in the Ventro Lateral nuclei.
INPUT from Basal Ganglia + Dentate Nuc. Cerebellum OUTPUT to Motor (4) and Premotor (6) Cortex
Describe afferent and efferent pathways involved in the Centro Medial nuclei .
IN from Reticular Formation & Basal Ganglia OUT to Cortex (diffusely : Centro Medial to 4 & 6)
Describe afferent and efferent pathways involved in the Dorso Medial nuclei.
IN from Prefrontal Cortex & Limbic System OUT to Prefrontal Cortex Dorso Medial deals with affect/emotion and foresight
Mania due to… or substance induced mania
secondary mania
What is rapid cycling in Bipolar Disorder ?
defined as 4 or more mood episodes/year.
describe atypical depression
Excessive sleeping Increased eating
Teen atypical depression may be first sign of what disorder?
bipolar disorder
What can result from the use of Lithium to treat bipolar disorder?
hypothyroidism
Hypothyroid symptoms are similar to ____.
depression
-For at least 2 years, the presence of hypomanic symptoms that do not meet criteria for full hypomanic episode and numerous periods of depressive symptoms that do not meet criteria for full major depressive episode. -Results in distress or functional impairment. -A chronic, smoldering form of bipolar illness.
cyclothymic disorder
What do you look for to determine if a patient is in a manic state?
DIG FAST need 3 of these 7: Distractible Increased activity/psychomotor agitation Grandiosity/Super-hero mentality Flight of ideas or racing thoughts Activities that are dangerous or hypersexual Sleep decreased Talkative or pressured speech
Major depressive episodes & hypomanic episodes would give you the diagnosis of what?
Bipolar II
Manic episode, with or without an episode of major depression.
Bipolar I
What are the therapeutic levels of Lithium you should aim for?
Therapeutic= 0.8- 1.2 mEq/L
Toxic levels of Lithium may require hemodialysis. Why?
b/c lithium is a salt that will be excreted through the kidneys–> too much would put major stress on kidneys to get rid of it
Adverse effects of lithium:
Tremor Sedation Ataxia Aphasia Thyroid enlargement Reversible nephrogenic diabetes insipidus Edema Acneiform skin eruptions Teratogenic: Ebstein anomaly
What can increase lithium levels?
Dehydration NSAIDs Angiotensin-converting enzyme inhibitors (ACEIs) Diuretics: Thiazides and Loop
What can decrease lithium levels?
Caffeine Theophylline
What are the therapeutic levels of Valproate you should aim for?
Therapeutic: 50-100 μg/mL
What are the adverse effects of Valproate?
GI: nausea, vomiting, diarrhea, anorexia Tremor – resembles benign tremor Sedation Hair loss Pancreatitis Leukopenia and thrombocytopenia Hepatotoxicity Weight gain Polycystic Ovarian Syndrome Birth defects: Neural tube defects and others
What are the therapeutic levels of Carbamazepine & Oxcarbamazepine you should shoot for?
Therapeutic 4-12 mcg/mL
What are the life threatening adverse effects of Carbamazepine & Oxcarbamazepine?
Rare Aplastic Anemia, agranulocytosis Rare Stevens Johnson Sd SIADH with hyponatremia
What are the life threatening adverse effects of Lamotrigine?
Rare Stevens Johnson Sd RASH SO YOU HAVE TO TITRATE VERY SLOWLY
What are the two essential symptoms (have to have at least 1 to land the diagnosis) of depression?
- Depressed mood – may present as irritability in children, teens, and men 2. Anhedonia (inability to feel pleasure)
What are the major symptoms of depression?
SIG E CAPS Sleep Interests (anhedonia) Guilt (emphasize hopelessness, helplessness, worthlessness) Energy Concentration Appetite Psychomotor slowing or agitation Suicidal ideation (including thoughts of death)
If a patient presented with depression along with delusions and hallucinations, what would be the diagnosis?
depression with psychotic features
If a patient presented with depression along with Mutism, immobility or motor overactivity, posturing, or echolalia, what would be the diagnosis?
Depression with catatonia
If a patient presented with depression along with an increase in appetite, increasing sleep and heaviness in arms or legs , what would be the diagnosis?
Depression with atypical features
If a patient presented with depression that was worse in the morning along with an early wake up and loss of pleasure or reactivity , what would be the diagnosis?
Depression with melancholic features (classical description)
If a patient presented with depression onset during pregnancy or in the 4 weeks following a delivery , what would be the diagnosis?
Depression with peripartum onset
If a patient presented with depression that had regular temporal relationship between onset and a particular time of the year , what would be the diagnosis?
Depression with seasonal pattern
Depression may be caused by medical illness. List the 2 prominent examples.
Carcinoma: pancreas Vitamin deficiency: pernicious anemia – vitamin B12 HYPOthyroidism
can cause depression and mania
steroids
Depression can be caused by medical treatments. List the ones we have to pay special attention to.
Antihypertensives Propranolol Reserpine Methyldopa Interferon Opioids Steroids CNS depressants Alcohol Barbiturates Benzodiazepines Clonidine
Neurotransmitter that deals with your drive.
dopamine
Neurotransmitter that deals with your impulse control.
serotonin
Neurotransmitter that deals with your energy and interest.
norepinephrine
what are the effective psychotherapies for depression?
Cognitive Behavioral Therapy, Behavioral Therapy, Interpersonal Therapy (IPT)
What are tricyclic antidepressants commonly used for today?
insomnia and relieving chronic pain
What drug class do you not combine with SSRIs?
MAOI’s; can cause serotonin toxicity
What are the only two antidepressants that have no sexual side effects?
Bupropion (Welbutrin) and Mirtazapine
What’s the mechanism of action of Mirtazapine?
-Blocks H1 (histamine) receptors -Blocks presynaptic α2 receptors leading to increased release of NE
Which antidepressant has sever hepatotoxicity?
Nefazodone
This antidepressant has the unfortunate side effect of causing priapism (erect penis won’t go flaccid–>medical emergency).
Trazodone
What antidepressant would you not prescribe if your patient didn’t need to put on any weight?
Mirtazepine
What are the prototype MAOI’s?
Phenelzine and tranylcypromine
Rapid (as soon as 40 min after IV administration) and sustained (on the order of months) antidepressant effects in otherwise treatment-resistant patients
Ketamine
only SSRI approved for depression in children and adolescents
Fluoxetine
Ophthalmic artery is ____ in location.
subarachnoid
What are the signs a patient in a manic state displays?
During the mood disturbance, three or more of the following are present. Use the DIG FAST mnemonic: Distractibility Irresponsible and erratic behavior Grandiosity (inflated self-esteem) Flight of ideas (racing thoughts) Activity is increased and goal directed Sleep (decreased need) Talkativeness or pressured speech
Ingestion of what medications can lead to serotonin syndrome?
Remember the drugs causing serotonin syndrome with the following mnemonic: Sinners SELl Drugs That MAke ME TRIP ON the TRAM LINE St John’s Wort (Sinners and Saints!) SELective Serotonin Reuptake Inhibitors Dextromethorphan TCAs MAO inhibitors MEperidine TRIPtans ONdansetron TRAMadol LINEzolid
What might result from a lesion of the intralaminar nuclei of the thalamus?
The intralaminar nuclei are several cell groups enclosed within the internal medullary lamina. The exact function of these nuclei is not yet fully understood. However, lesions of the intralaminar nuclei can result in disturbances in attention and arousal
What is the function of the basal ganglia?
The basal ganglia are involved in excitatory and inhibitory cortico-thalamic feedback loops that modulate motor activity.
Congenital absence of pain is due to genetic mutation of one type of _____.
voltage gated sodium channel
Allodynia is pain due to ____.
activation of a normally non-nociceptic receptor
The wheal of the triple response is due to _____.
exudate from capillaries and venules
This substance acts on mast cells causing degranulation.
substance P
causes plasma extravasation and edema
histamine
Primary hyperalgesia is due to sensitization of _____.
nociceptive receptors
Secondary hyperalgesia is due to _____.
upregulation of receptors in CNS
Allodynia is due to sensitization of _____.
spinal cord neurons and thalamic cells
Ordinary inflammatory pain is ____ pain.
nociceptive pain
Pain due to injury to the CNS is ____ pain.
neuropathic
Pain caused by cancer is ____ pain.
mixed pain (nociceptive and neuropathic)
Which fiber types convey nociceptive information?
C and A-delta
Pain due to nociceptors in the kidney is referred where?
flank region on same side
Nociceptive signals activate the ARAS (ascending reticular activating system) through synapses in which thalamic nucleus or nuclei?
intralaminar nuclei
Which neurotransmitter is released by the pituitary gland during high stress?
endorphin
Chronic pain can be alleviated by a lesion in which thalamic nucleus?
intralaminar
an increase in the pain caused by a normally painful stimulus
hyperalgesia
pain caused by a stimulus that is normally not painful
allodynia
“pins and needles” sensations such as felt when an arm or leg “goes to sleep”
paresthesias and dysesthesias
What is the triple response to nociception from skin?
1) redness at lesion- due to capillary dilation 2) flare- spread of redness around lesion due to axon reflex 3) wheal- raised region due to exudation of fluid from capillaries and venules
produces dilation of peripheral blood vessels - redness
CGRP (calcitonin gene related peptide)
convey secondary, aching pain
C fibers
convey primary, localization pain
A-delta fibers
What’s the advantage of CT angiography over MR angiography?
CTA can show precise demonstrations of calcifications in the vascular wall
Which artery extends through the Sylvian fissure?
middle cerebral artery
What is the most medial point of all the branches that come off of MCA?
Sylvian point
What is shown in this image?
Arteriovenous malformation
Cytotoxic edema involves ______.
grey and white matter in infarct
Vasogenic edema involves _____.
involves white matter as edema spreads typically in abscess or tumor
Best for looking at anatomy.
T1 MR
Best for looking for pathology.
T2 MR
What is the only sensory system that does not go through the thalamus in order to get to the cortex?
olfactory system
produces ACh and is thought to have a role in Alzheimer’s disease
nucleus basalis
What does the arcuate fasciculus connect?
Wernicke’s area to Broca’s area
What does the uncinate fasciculus connect?
the temporal lobe with the inferior part of the frontal lobe
Sensory cortices will have more of which type of cells in their cytoarchitecture?
granular cells
Parinaud’s Syndrome is an inability to move the eyes up or down. What causes it?
Caused by a tumor of the pineal gland
lesions of what nucleus can cause hemiballismus (wild flinging movements)?
subthalamic nucleus
