Sedation, Epilepsy, Memory (oh my) Flashcards
In classical conditioning, what is a conditioned stimulus?
a stimulus that used to be neutral that now provokes a conditioned response after being linked to an unconditioned stimulus
ex. a whistle that is consistently blown while giving a dog food will eventually make the dog drool on its own even without food present
What drug binds at omega receptors on GABA?
benzodiazepines (between gamma and alpha subunits)
What benzodiazepine is used for refractory status epilepticus?
midazolam (IV infusion)
What are some connections to the limbic system?
limbic lobe, olfactory system, amygdaloid connections
What is eszopiclone used for?
sleep maintenance insomnia
What seizure disorder can phenobarbital be used for?
refractory status epilepticus (IV infusion)
What is the pathway of the paralimbic cortex?
cingulate gyrus –> paraolfactory gyrus –> orbitofrontal cortex –> insula –> uncus –> parahippocampal gyrus –> cingulate gyrus
What is a “hypnotic” agent?
an agent that causes drowsiness and sleep
What is the main difference between mild and major neurocognitive disorder?
modest impairment (not significant)
does not interfere with daily life
What are the downsides of phenytoin?
non-linear pharmacokinetics with high protein binding (hard to predict doses)
side effects: sedation, imbalance, diplopia, dizziness, gum hyperplasia, hirsuitism
more serious effects: hepatotoxicity, bone marrow suppression, rash
Which anti-convulsants can also be used for neuropathic pain?
gabapentin, carbamazepine, pregabalin
What is the concept of “extinction” in memory?
loss of responses to stimuli over time (ex. loss of stimuli conditioning)
failure of extinction may cause PTSD
What is dementia?
a generic term for a progressive decline of mental status to the point of interference with daily activities
What are the clinical features of mesial temporal lobe epilepsy?
seizures begin in childhood/adolescence
often a predisposing “hit” in the medical history (ex. trauma, infection)
often starts with generalized tonic-clonic seizures followed by typical focal seizures
associated with characteristic auras
usually requires surgery
What is a myoclonus?
brief, lightening-like single jerk of a muscle or muscle group
What is the difference between childhood absence epilepsy and juvenile absence epilepsy?
juvenile has a later onset (around puberty) and does not always go away (unlike the childhood form)
What is the definition of epilepsy?
A set of disease states characterized by a predisposition to unprevoked seizures
What is the metabolism of suvorexant?
CYP3A4 followed by glucuronidation
What is the mechanism of valproate?
acts on T-type Ca2+ channels and may also act on Na+ channels and increase GABA levels
Which anti-convulsants can also be used for migraines?
valproate, topiramate, zonisamide
What is positive reinforcement?
providing a reward to increase behavior
ex. pushing a lever to get a treat
In classical conditioning, what is a conditioned response?
a response to a conditioned stimulus
ex. salivation by a dog in response to a whistle that has been linked to presentation of food
When is epilepsy onset most common?
in childhood or in old age (bimodal peaks)
What are the appropriate pharmacological treatments for alcohol withdrawal?
benzodiazepines (diazepam, lorazepam,and oxazepam)
What is zonisamide?
a drug that acts on Na+ channels, Ca2+ channels, and carbonic anhydrase inhibition
used for all seizure types
What symptoms are associated with Wernicke-Korsakoff syndrome?
Wernicke symptoms: ataxia, eye movement abnormalities, confusional states
Korsakoff symptoms: longer term; anterograde and retrograde amnesia; poor judgment, initiative, impulse control, and sequencing tasks
can cause “spurious answers” to questions
What is C?
orbital frontal gyri + insula (not visible)
What are the side effects of topiramate?
kidney stones (most common)
paresthesias, sedation, cognitive impairment
What is the metabolism of the long acting ___azepams?
phase 1 metabolism by CYP2C19 and CYP3A4 to active intermediates that are hydroxylated (LOTs) and then glucuronidated
What are the side effects of valproate?
GI upset, sedation, cognitive impairment
hepatic failure, thrombocytopenia, and pancreatitis
highly teratogenic
What is a “sedative”?
a drug that reduces the excitatory responsiveness to external stimuli and produces a calming effect
What is a forgetting curve?
A curve that represents the fact that information loss is time dependent
loss decreased by sleep and reviewing
Which type of dementia is associated with inability to look down voluntarily?
progressive supranuclear palsy
What is the difference in dose of drug vs. biological effect for benzodiazepines compared to barbituates or propofol?
benzodiazepines general saturate at low anaesthetic levels (they function by increasing opening rate of chloride channels, which is self-limiting)
barbituates and propofol continue sedating to the point of coma or death at high doses (they function by increasing the opening duration of chloride channels, which is not self-limiting)
Which benzodiazepines are used for sedation and anaesthesia during medical procedures?
midazolam, diazepam
Which type of epilepsy is associated with generalized tonic-clonic seizures that only occur at night and resolve after puberty?
benign rolandic epilepsy
What is tigabine? What is it used for?
selective GABA reuptake inhibitor
used for partial seizures (but not often)
What are the main functions of the limbic system? What structures are associated with each function?
HOME
Homeostatic functions (including autonomic and neuroendocrine control) - hypothalamus
Olfaction - olfactory cortex
Memory - hippocampal formation
Emotions and drives - amygdala
What is the clinical presentation of frontal lobe epilepsy?
seizures most often at night
usually not associated with arua or post-ictal confusion
involves bizarre and complex automatisms
What are the steps of the papez circuit?
parahippocampal gyrus (entorhinal cortex) –> hippocampus (subiculum) –> fornix mamillary bodies –> anterior thalamic nuclei –> cingulate gyrus –> back to the parahippocampal gyrus
info from the cortex enters this circuit through the perforate pathway and parahippocampal gyrus
What is the cause of absence seizures?
abnormal cortico-thalamic interactions with the reticular nucleus of the thalamus acting as the pacemaker for cortical neurons and thalamic relay neurons
What are the spatial patterns of memory consolidation?
starts in the hippocampus, spreads out and gets incorporated into the cortex
When is a seizure automatically a medical emergency?
when it lasts a long time and becomes status epilepticus
What is levetiracetam?
unknown mechanism anti-convulsant
minimalside effect profile, minimal drug interactions
What is the clinical presentation and gross pathology of progressive non-fluent aphasia?
clinical presentation: deficits in expressive language, agrammatisms, apraxia of speech
gross pathology: atrophy of interior frontal and insular cortex, associated with both FTD-tau and FTD-TDP
What is A?
cingulate gyrus
What is working memory?
memory that involves retention of information for brief periods of time that is limited in time and capacity
What condition is associated with temporal lobe epilepsy?
mesial temporal sclerosis
What non-benzodiazepine and non-ZAZOLES agents are used to treat insomnia?
barbituates, scopolamine (antimuscarinics), diphenhydramine (antihistamines), ethanol
What is the function of the dentate gyrus?
thin cortex that acts as the input station for hippocampal information (from the cortex)
cortex –> entorhinal cortex –> dentate gyrus (via perforant pathways) –> hippocampus
What are the two general pathways from the cortex to the hippocampus?
alvear pathway (via alveus) and perforant pathway (via dentate)
What are the treatments for frontotemporal lobar degeneration?
SSRIs, non-pharmacological interventions (reward based therapy, speech therapy, PT)
What is E?
parahippocampal gyrus
What is the treatment for mesial temporal lobe epilepsy?
usually requires surgery (anteromesial temporal lobectomy)
What is the utility of topiramate?
all seizure types (except absence seizures)
migraines, pain, and essential tremor
What benzodiazepines are used to treat muscle spasms?
diazepam and clonazepam
What is the clinical presentation and gross pathology of semantic dementia?
clinical presentation: lack of understanding or knowledge of words, objects, faces, and other items; can also have verbal deficits or trouble recognizing faces and behavioral changes
gross pathology: bilateral, frequently asymmetric atrophy of the temporal neocortex, associated with FTD-TDP
What sleep pattern changes are associated with insomnia?
longer latency period before sleep, multiple awakenings throughout the night, decreased total sleep tie, reduced slow wave sleep
What are the main side effects of vigabatrin?
visual field loss (but maybe not as bad as reported)
headaches, dizziness, depression, etc.
can also cause psychosis or other psychiatric disorders
What benzodiazepines are used for acute seizures?
lorazepam, diazepam
What is the clinical presentation of corticobasal syndrome?
clinical presentation: asymmetric motor signs and cortical signs
usually associated with FTD-Tau and with FTD-TDP
What are the components of the hippocampal formation?
dentate gyrus, hippocampus, subiculum
What is the effect of MT2 agonists?
used to treat non-24 hour sleep-wake disorder in patients that are blind
ex. tasimelteon
What is F?
fornix
Which anti-convulsants can also be used for bipolar disorder?
lamotrogine, valproate
What is the structure of the hippocampus?
A structure along the floor of the inferior horn of the lateral ventricle - becomes continuous with the fornix below the splenium of the corpus callosum
What are the side effects of lamotrigine?
headache, insomnia, and rash (stevens-johnson syndrome)
What is the effect of GABA antagonists? What are examples of competitive, non-competitive, and uncompetitive inhibitors of GABA-A?
they are convulsants
competitive: bicuculline (binds at GABA site)
non-competitive: picrotoxin (binds at the channel region of all subunits)
uncompetitive: penicillin (blocks open channel)
How are ZAZOLES metabolized?
With CYP3A4
What are the core features of lewy body disease?
1) fluctuations in attention and alertness
2) motor changes of Parkinsonism
3) recurrent visual hallucinations
* must have at least 2/3*
What types of seizures is carbamazepine used for?
partial and generalized tonic-clonic seizures
can make absence, atonic, and myoclonic seizures worse
What is the effect of HSV1 on the limbic cortex?
HSV1 has a tropism for the limbic cortex and can cause encephalitis of the limbic areas
leads to profound anterograde amnesia
What is the main indication for clobazam?
to treat drop attacks in children
Which type of dementia is associated with asymmetric vision, balance, speech, and swallowing problems?
corticobasal degeneration
What are the side effects of barbituates?
sedation, respiratory depression, cognitive impairment, hepatotoxicity, allergic rashes
What is the mechanism of eslicarbazepine?
potent inhibition of sodium channel activity
What is zaleplon used for?
good for sleep onset insomnia
What anti-convulsants are selective CYP3A inducers?
felbamate, topiramate, oxcarbazepine
What is the metabolism of ___azolam drugs?
metabolized by CYP3A4 before glucuronidation
What are the clinical features of lennox-gastaut syndrome?
mental retardation (usually severe)
multiple seizure types (GTC, myoclonic, atypical absence, atonic, focal)
seizures are not controllable
What is the effect of MT1 agonists?
reduce sleep latency (but do not alter the number of times waking up) in patients with insomnia
ex. ramelteon
What is positive punishment?
utilizing an aversive stimulus to decrease behavior
ex. shock delivered every time lever is pressed
What types of auras are associated with mesial temporal lobe epilepsy?
aura caused by limbic system malfunction
rising epigastric sensation (insular cortex)
deja vu (temporal neocortex)
olfactory hallucination (uncus)
sudden emotion (amygdala)
perceptual distortions (temporo-parieto-occipital association areas)
autonomic symptoms (insular cortex)
Where is the insula/insular cortex?
underneath the frontal lobe laterally
Where do benzodiazepines bind on the GABA-A receptor?
at the junction of the alpha and gamma subunits
What is the general mechanism of benzodiazepines?
allosteric modulation of the GABA-A receptor, which leads to increased fequency of Cl- channel opening and membrane hyperpolarization
What is zolpidem used for?
normalizes sleep without producing drowsiness
used for sleep onset insomnia and in patients who awaken frequently during the night
What structures are linked to explicit/episodic memories?
hippocampus and limbic system
What are the clinical features of neocortical epilepsy?
seizures that have a focal onset anywhere in the cortex (except mesial temporal lobe)
can have auras or can spread quickly and become generalized tonic-clonic seizures
What conditions can make benzodiazepines dangerous?
if patients have obstructive sleep apnea or COPD
when used in combination with opioids or ethanol