Exam #2 Flashcards
Treatment for Bipolar disorder
Normal
Anti seizure drugs
Antipsychotics
Normal: lithium Anti seizure drugs: - valproic acid - carbazepime - Lamatrigine Antipsychotics: - Quetiapine
Lithium MOA
- activates GABA release
- inhibits glutamate and dopamine
- inhibits phosphoinositol cascade (IP3 and DAG pathway)
- Inhibition of glycogen synthase kinase-3 (GSK-3) leading to neuroprotection
Lithium therapeutic range
0.6-1.5 mEq/L
Lithium Pharmokinetics
Competes w Na+ for tubular reabsorption in the kidneys (Lithium can be in by Na+ loss often seen in diuretic use)
-diuretics can inc lithium concentration
Lithium Adverse Effects
Hypothryroidism (weight gain, dry skin, hair loss, and constipation)
Tremors
Ataxia (ESP WHEN PAIRED W ATYPICAL PSYCHOTICS)
Nephrogenic diabetes insipidus (dec response to ADH leading to polyuria)
Nausea, vomiting, diarrhea
PREGNANCY = Ebstein anomaly
Carbamazepine CYP
inducer
Monoamine Hypothesis
Depression resulting from pathological dec in serotonin, NE, and/or dopamine neurotransmission
Neurotropic Hypothesis
Loss of neurotrophic support leading to depression (Brain derived neurotrophic factor)
Hypothalamic-Pituitary-Adrenal Axis Dysregulation
Elevated levels of cortisol and CRH
Thyroid Dysregulation
Depression associated w hypothyroidism or hyperthyroidism
SSRIs names
Fluoxetine Paroxetine Sertraline Citalopram Escitalopram Vilazadone
SNRIs names
Duloxetine
Venlafaxine
Milnacipran
Levomilnacipran
initial inhibition of SERT induces
activation of 5-HT1A and 5-HT1D autoreceptors
TCS names
Imipramine
Amitriptyline
TCA nonselective effects
Antimuscarinic
Antihistaminic
Alpha-blockade
5-HT2 Antagonists
Trazodone
Nefazodone
5-HT2 Antagonists Nonselective effects
Antimuscarinic, antihistamine, alpha-blockade
MOA-A and MOA-B irreversible inhibitors
Phenelzine
Tranylcypromine
MOA-B irreversible inhibitor only
Selegiline
bupropion MOA
inhibits the norepinephrine transporter (NET) and the dopamine transporter (DAT)
Mirtazapine moa
alpha-2 inhibition increases presynaptic release of serotonin and norepinephrine
Trazodone moa
serotonin modulator (antagonizes 5-HT receptors and inhibits 5-HT reuptake)
increased risk of suicide between children, adolescents and young adults. SSRI SNRI TCA MOA inhibitor Atypical
SSRIs: -Escitalopram -Fluoxetine SNRIs: -Duloxetine TCAs: -Imipramine MOA inhibitor: -Phenelzine Atypical: -Bupropion
Schizophrenia pathology
- Inc dopaminergic activity (D2 receptor)
- Inc serotonergic activity (5-HT2A and 5-HT2C)
- Diminished GABA activity leading to hyperstimulation
Typical antipsychotics names
Chlorpromazine
Haloperidol
Atypical antipsychotics names
Chlorpromazine
Haloperidol
Typical antipsychotics MOA
D2 antagonist
Atypical antipsychotics MOA
Preferential antagonism of 5-HT2A receptors; some D2 antagonist action
Aripiprazole MOA
partial agonist at D2
5-HT2A
Transducer:
Effect:
Transducer: Gq
Effect: PKC mediated reduction of Ca2+ and Na+ conductance
5-HT2C
Transducer:
Effect:
Transducer: Gq
Effect: PKC mediated reduction of Ca2+ and Na+ conductance
Dopamine Inhibition
α-adrenergic Inhibition
Muscarinic Inhibition
Histamine (H1) Inhibition
Dopamine Inhibition: -extrapyramidal reaction -hyperprolactinemia α-adrenergic Inhibition: -orthostatic hypotension Muscarinic Inhibition -urinary retention -constipation -blurred vision -dry mouth Histamine (H1) Inhibition: -sedation
antipsychotics w highest Dopamine Inhibition
haldol
Neuroleptic Malignant Syndrome
Life threatening disorder most commonly associated w/ typical antipsychotics with high affinity for D2 receptors Symptoms: -Hyperthermia -extreme muscle rigidity -tachycardia
typical psychotics adverse effects
Weight gain
QT prolongation
Sedation
Diazepam MOA
GABAa agonist that hyperpolarizes the cell via opening of Cl- channels
Baclofen MOA
GABAb agonist which hyperpolarizes via:
- Closure of pre-synaptic Ca+2 channels
- Increased post-synaptic K+ channels
- Inhibits dendritic Ca+2 influx channels
Tizanidine MOA
alpha2 adrenergic agonist in spinal cord (pre and post synaptic inhibitor in spinal cord, inhibits nociceptive transmission in dorsal horn)
Tizanidine contraindication
Potent CYP1A2 inhibitor (don’t take w fluvoxamine/ciprofloxacin)
Cyclobenzaprine adverse effects
Concomitant MAO
Acute recovery phase of MI
Patients w heart block or congestive heart failure
Cyclobenzaprine adverse effects
Hallucinations
Dantrolene MOA
blocks RYR1 channels in SR of SKM
Botulinum Toxin MOA
inhibits synaptic exocytosis of vesicles via cleaning SNAP-25 or synaptobrevin-2
Malignant hyperthermia treatment
Dantrolene
Dantrolene adverse effects
Hepatotoxicity
Contraindication concomitant use of meperidine
Selegiline
Rasagiline
Amantadine MOA
increase dopamine release and decrease dopamine uptake (exact MOA unknown)
Amantadine adverse Effects
Orthostatic hypotension
Urinary retention
Peripheral edema
Benztropine MOA
muscarinic and histamine antagonist
Benztropine contraindication
Children <3 yo
Trihexyphenidyl MOA
muscarinic and histamine antagonist
Adjunctive PD therapy w on-off phenomena
Selegiline
Trihexyphenidyl adverse effect
Glaucoma
Pramipexole MOA
D3 agonist
Cylclobenzaprine contraindication
Concomitant MAO
Acute recovery phase of MI
Patients w heart block or congestive heart failure
Vigabatrin MOA
Irreversibly inhibits GABA-T
Vigabatrin adverse effects
Permanent Visual field loss (Black Box)
Tiagabine MOA
selective inhibitor of the GAT-1 GABA transporter
Tiagabine adverse effects
Dizziness, drowsiness, nervousness, lack of concentration
Perampanel MOA
non-competitive antagonist of the AMPA receptor on post-synaptic neurons, a main mediator of synaptic excitation in the central nervous system
Perampanel adverse effects
aggression, hostility, irritability, and anger
**Alcohol use may exacerbate the level of anger
Selegiline
Rasagiline adverse effects
anxiety and insomnia
what special about Oxcarbazepine
no cyp interactions
Phenytoin adverse effects
diplopia
ataxia
gingival hyperplasia
hirsutism
Lamotrigine indication
Conversion to monotherapy in adults with partial-onset seizures
Topiramate adverse effects
Decreased serum bicarbonate
impaired expressive language function
Topiramate contraindication
alcohol use
patients with metabolic acidosis
Valproic Acid/Valproate/Divalproex contraindication
pregnancy
liver failure
Lacosamide MOA
Selectively binds fast-inactivated state of sodium channels
Ethosuximide MOA
inhibition of low-voltage activated T-type calcium channels in thalamocortical neurons
Lamotrigine adverse effect
insomnia
Gabapentin MOA
avidly binds to alpha-2-delta-1 (α2δ) subunit of voltage-gated calcium channels
Gabapentin adverse effects
somnolence
ataxia
Phenobarbital MOA
- positive allosteric modulators of GABAa receptors at low concentrations
- directly activate GABAA receptors at higher concentrations
Levetiracetam MOA
binds selectively to SV2A, a ubiquitous synaptic vesicle integral membrane protein, reducing the release of glutamate during trains of high-frequency activity
Perampanel MOA
non-competitive antagonist of the AMPA receptor on post-synaptic neurons, a main mediator of synaptic excitation in the central nervous system
Perampanel adverse effect
aggression, hostility, irritability, and anger
Ezogabine MOA
binds the KCNQ voltage-gated potassium channels
Inhibitors of Brain Carbonic Anhydrase
Topiramate
Zonisamide
Known teratogens or associated with congenital malformations
Valproate
phenobarbital
topiramate
Ethosuximide adverse effects
Fatigue GI distress Headache Itching (and urticaria) SJS
ezogabine adverse effect
pigment discoloration
Levetiracetam adverse effect
personality changes
Tabes dorsalis effects
Dorsal columns: proprioception, vibration, ataxia
Doral roots: reflex
Troheryma whipplei association
endocarditis
Leptospira uniterrogans symptoms
meningitis
hepatitis
conjuntivitis
acute renal failure w hematuria
Leptospira uniterrogans treatment
doxycycline
Borrelia burgdorferi serology
ELISA IgM/IgG antibody
followed by western blot
Nocardia can causes
parenchymal brain abscesses
basilar meningitis
Tb
cavernous sinus cranial nerves
3,4,V1,V2,6
internal carotid artery
prosthetic devices meningitis
Staph epi
Staph aureus
cochlear implants
strep pneum
CSF leaks
strep pneum
mycotic aneurysm
staph aureus
salmonella
paraspinous abscess
staph aureus
bacterial meningitis treatment
neonate
normal
>60
neonate: Ampicillin + Gentamicin + Cefotaxime
normal: ceftriaxone + vancomycin
>60: ceftriaxone + vancomycin + ampicillin
skin popping
clostridium
HSV-1 on EEG
slow, sharp spikes
“Ghost” or Mollaret’s cells
HSV
CMV associations
myelitis
polyradiculopathy
CMV treatment
gancyclovir
Primary CNS lymphoma in HIV patient
solitary, ring enhancing lesion in white matter usually next to ventricle
HHV-6 roseola symptoms
child w high fevers, seizures, and macular-papular rash beginning at torso and spreading to the extremities
colorado tick fever virus (dengue fever) symptoms
saddleback/biphasic fever
Chikungunya virus symptoms
rash
inflammatory arthritis
**severe arthralgias and arthritis that can last for weeks-years
zika virus symptoms
conjunctivitis
rash (including palms)
arthralgia
in pacific florida or texas
Measles/Rubeola causes
subacute sclerosing panencephalitis
Naegleria fowleri work up
check both centrifuged and non uncentrifuged CSF
Rhabdovirus histo
bullet shaped
negri bodies
Rhabdovirus encephalitic symptoms
hyperpyrexia alternating to hypothermia
hydrophobia
aerophobia
hypersalvation
Rhabdovirus paralytic symptoms
mimicking guillian barre leadings to ascending paralysis
crypto treatment
flucytosine + amp B
coccidiodes treatment
fluconazole
aspergillus
elevated beta-D-glucan
mucomycosis
negative beta-D-glucan
eosinophilic meningits
angiostrongylus cantonensis
acanthomeoba
spikey
hippocampus controls
episodic memory and spatial maps
entorhinal cortex
declarative memory and memory consolidation
hyperphosphorylate tau
CDK5
GSK3B
CRMP2
frontotemporal lobe dementia
aka pick disease
TDP-43
Neisseria meningitidis agars
Blood agar
Chocolate agar
Mueller-Hinton agar
Thayer-Martin
Neisseria meningitidis associations
DIC
Waterhouse-Friderichson syndrome
CSF adenosine deaminase means
TB
Familial fatal insomnia
location
mutation
diagnosis
location: thalamus
mutation: PRNP
diagnosis: thalamic hypometabolism on PET scan
Huntington mutation
CAG repeat in HTT gene on chromosome 4
Lewy body dementia location
midbrain
Chronic encephalopathy histo
tau protein chains that start in gray matter
Glutamate channels
GABA channels
Glutamate: Na+ open, K+ channels close
GABA: Cl- into cell, K+ channels open
GABA is made how
Glucose -> alpha ketoglut -> glutamate -(GAD-B6)> GABA
glutamate recycle patoway
glutamate that is not used is broken down to glutamine via glutamine synthase in astrocytes it is then transferred to neuron where it is converted back to glutamate
tyrosine pathway
diet/phenylalanine -> tyrosine -> DOPA -> dopamine -> NE -> epi
glutmate receptors and type
NMDA
AMPA
KA
ionotropic (ligand gated channel)
NDMA
requires glycine and glutamate for activation
GABAa
GABAb
GABAa: inotropic (inc Cl- influx)
GABAb: metabotropic (G protein, dec Ca2+ and activated K+ channels)
alpha1, beta
alpha 2
alpha1, beta: excititory
alpha 2: inhibitory
5HT3
inotropic
H1
H2
H1: Gq
H2: Gs
multiple system sclerosis def and hist
autonomic nervous system and movement dysfunction
histo: accumulation of alpha-synuclein
MS primary progressive
no history of attack, slow insidious progressive worsening
RR w secaondyr progression
slow progressing worsening after initial history of “relapsing remitting” form
progressive muscular atrophy
ALS with w mainly LMN involvement
primary lateral sclerosis
ALS w mainly UMN involvement
kugelberg-welnader disease
childhood/adolescents w LMN
bind GABAa
benzos barb alc etomidate propofol
subdural chronic and acute treatment
acute: 2 incision
chronic: burr hole
encephalitis CSF
RBC present
concussion
rotational/angular force
decorticate
decerebrate
decorticate: arms flexed to chest
decerebrate: arms ext to side
vasogenic edem
disruption of BBB
cervicaly myelopathy effect
arms>legs
nueromyelitis optica
long lesion of demyelination in spinal cord involving optic nerve
- anti aquaporin 4 antibody
- more segment involved than MS (>3)
- more aggro than MS
Acute disseminated encephalomyelitis
one attack that leaves (not reemitting like MS)
Acute transverse myelitis
one attack that leaves deficits
rubrospinal tract
forelimbs
SPECT
dopamine transporter
Parkinson’s induced by
Basal gang
Latrogenic
Basal gang: dec dopamine, inc Ach
-abnorma SPECT
Latrogenic: drug induces
-normal SPECT
ALS prognosis
bulbar (CN) has worse prognosis than manual (extremities)
diffuse axonal injury
global brain injury due to high velocity deceleration
-micro/macro transaction of neurons
rate limiting step for tyrosine pathway
tyrosine hydroxylase
tyrosine -> DOPA
NE location
LC
watershed infarcts manifestation
paraplegia to legs
penumbra
ischemic core
penumbra: enough blood to keep tissue alive but electrically silent
ischemic core: permanent tissue damage
brain infarcts
acute
chronic
acute:
-edema
-no gliosis
-RBCs
chronic:
-no edema
-hemosiderin
-gliosis
-liquification necrosis
inc subdural hematoma mortality
inc age
anticoagulants
unhelmeted
best montage for seizures
referential
alpha waves
8-13 hz
alpha rhythm
post prominent alpha waves
surpassed w eye opening
delta waves
<3 hz
absent seizure is a
generalized seizure
clonus
rhythmic fast flexion and slow extension
myoclonus
sudden movente w no rhythm
Kidling
focal simulation leads to continued intermittent seizures after simulation is removed
mirror focus def
most common location
secondary epileptic foci develop in the contralateral hemisphere homotopic area
-temporal/frontal love epilepsy (occipital not likely)
post titanic potentiation
inc frequency of miniature excitatory post synaptic potential w no affect on amplitude
long term potentiation
persisting strengthening of synaptic signaling based on recent patterns of activity
-long lasting gin in signaling transmission between two neurons
tuberous sclerosing complex
cortical tubers
seizures
subependymal nodules
giant cel astrocytomas
Down syndrome most common seizure
tonic clonic
PKU EEG
slowing, epileptiform discharge, or hyper arrhythmic patterns
dravets syndrome
100s of seizures
epilepsy mutations commonly include
K+, Na+, Ca2+ channels
myoclonus epilepsy
ragged red fibers
mitochondrial dna mutation