Exam 3 lecture 7 Flashcards by Matti Daniel

What are the neurocognitive domains and how can they be used

Neurocognitive domains are diagnostic criteria. Each domain defines exoectation for major or mild NCD

Complex attention- sustained/divided attention, processing speed
Learning and memory- immediate/recent memory, very long term memory
perceptual/motor- visual perception/praxis
executive function- planning decision making, working memory, flexibility
language- expressive and receptive language
social cognition- recognition of emotion, range of behavior

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difference between dementia and delirium

Dementias- are deficits in learning and memory (long term and irreversible)
delirium is focused on attention (short term and reversible)

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define mild neurocognitive disorders

Evidence of modest cognitive decline from a previous level of performance in 1 or more cognitive domains

does not interfere with independence

not attributed to delirium episode

not explained by mental/medical disorder

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Define major neurocognitive disorder

Evidence of significant cognitive decline from a previous level or performance

interfere with independence

not attributed to delirium episode

not explained by mental/medical disorder

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types of NCD

alzheimers
vascular dementia
lewy body disease

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What are the reversible labs that lead to reversible cognitive decline

B12 or folate deficiency
hypothyroidism
CBC
electrolytes
LFT
infection
Depression

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Most frequently seen drugs that cause cognitive impairement

Skeletal Muscle Relaxants
* Tricyclic Antidepressants
* Bladder antispasmodics
* Antihistamines
* OTC allergy/cough cold
* Rx anti-emetics

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describe alzheimers, vascular dementia and lewy bodies if they were on a graph

Lewy bodies- up and down. Looks like it is getting better but gets worse

Vascular dementia- looks like a downward stair case. Has periods where there is no decline and periods where there is.

Alzheimers- constant decline

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options for treatment for NCDs

Cholinesterase inhibitors
NMDA receptor antagonists

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cholinesterase inhibitor FDAapproved for? what line of treatment? drugs?

FDA approved for mild to moderate and severe dementia
1st line and donepezil usually chosen 1st
Donepezil (Aricept)
◦ Rivastigmine (Exelon)
◦ Galantamine (Razadyne)

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NMDA receptor antagonists used for? FDA approved for? drugs?

Does not slow/prevent neurodegeneration
FDA approved in moderate to severe dementia only
not useful in mild-cognitive impairement

Drugs Memantine (Namenda)
◦ Donepezil/Memantine
(Namzaric)

tx causes 6-12 months in delay of alzheiners

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dosing of donepezil? side effects?
Dosing of galantamine? side effects?
dosing of rivastigimine? side effects?
dosing of memantine? side effects?
dosing of memantine/donepezil? side effectrs?

donepezil
initiate- 5 mg QD at bedtime
increase to 10 mg QD at bedtime after 4-6 wks
side effects- GI bleeding (caution with NSAIDs) N/V/D, bradycardia, syncope, weightloss
CYP 2D6 3A3/4 substrate

galantamine-
IR- 4 mg BID for 4 wks with breakfast and dinner
>16 mg/day not recommended for moderate renal/hepatic impairement

side effects- GI bleeding, weightloss, N,V,D, bradycardia, syncope, insomnia

rivastigamine
- dosing- initiate 1.5 mg BID. Take with meals to minmize GI side effects
toxicity- due to not removing previous patch everyday N/V/D (significant)

memantine
Dose adjustment required in severe renal impairment (CrCl= 5 – 29 ml/min) = Initiate 5mg once daily x 1 week, if tolerated, target dose = 5mg twice daily

side effects- Use with caution in patients with seizure disorder Dizziness, headache, hallucinations, insomnia, confusion, constipation Use with caution with carbonic anhydrase inhibitors and sodium bicarbonate – clearance of memantine is reduced by 80% if urine is alkalinized No P450 interactions

memantine/donepezil
On donepezil 10 mg only: start Namzaric 7/10 daily and increase by 7 mg increments as tolerated to 28/10 target dose once daily If on memantine 10 mg twice daily or ER 28 mg once daily, switch to Namzaric 28/10 with evening meal once daily Warning for vagotonic effects like bradycardia and heart block; increased risk of GI ulceration; diarrhea, nausea, vomiting; bladder outflow obstructions;

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Is combination tx more efficacious? What should we educate the pt about regarding drug tx of NCDs, how to titrate dose? Key concepts with regard to taking drugs?

Combination tx- more efficacious,

educate that there is expected progression of disease.

Titrate to highest dose based on side effects

key concepts- adverse effects are dose dependent
do not suddenly stop and start

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what are some antibody drugs that are used in dementia? eligibility to get these drugs?

Adenacumab and lecanemab

eligibility- require presence of amyloid beta pathology prior to unitiating

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non pcol interventions for dementia

Consider vision, hearing, and other sensory impairments
Cognitive stimulation (puzzles, problem solving, Sudoku) can have short-term benefits on cognition an QOL
Maintain a consistent, structured environment with appropriate stimulation
Provide frequent reminders and orientation cues
Reduce choices, keep requests simple, avoid complex tasks that lead to frustration
Monitor for sudden changes in cognition and functioning
◦ Could be delirium due to reversible cause (dehydration or urinary tract infection/pneumonia)

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behavioral interventions for dementia

Increase enjoyable activities – listen to music, light exercise, pet therapy
Redirect and refocus – reminiscence therapy
Increase social activities – keep them busy
Encourage activities that are appropriate to the individual patient’s functional level
Establish regular sleep habits
Make sure the environment is safe, calm, and predictable
Watch caregiver for signs/symptoms of depression

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agitation interventions

Recognize triggers – pain, fecal impaction, medical illness, boredom, depression, stressors Intervene early, recognize behavior
Outdoor activities more efficacious than antipsychotics for managing agitation and aggression (Watt, et al. Ann Intern Med 2019)
Maintain calmness in interactions, avoid arguing or trying to reason.
Avoid confrontation – meet the patient where they are and avoid forcing them into your reality – live in theirs unless is causes distress to them or others Introduce distraction techniques, turn attention to something pleasant
Minimize audio and visual stressors from the environment

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how to treat vascular dementia and lewy bodies

vascular dementias- cholinesterase inhibitors are recommended
lewy bodies- cholinesterase inhibitors and memantine

compare 2011 and 2017 seizure classifications

2011- partial vs generalized
under partial- simple and complex
under simple- motor, sensory, autonomic, psychic

under generalized- tonic, clonic, tonic-clonic, absence, atonic, myoclonic

2017- Split into focal onset, generalized onset, unknown onset
under focal onset- aware and impaired awareness
under generalized onset- motor (tonic clonic) non motor (absence)

unknown onset- motor (tonic clonic) and non motor

Mediactions that lower the seizure threshold at their usual doses

bupropion
Clozapine
theophyline
varenicline
Phenothiazine (antipsychotics)
CNS stimulants (amphetamines)

Medications that lower seizure threshold at high doses and impaired renal function

Carbapenems (imipenem)
Lithium
Mepridine
Penicillin
Quinolones
Tramadol

most common seizure type? what percent of patients will have good control with 1 drug? When is polytherapy necessary for epilepsy pts

partial seizures (whether simple or complex are most common)

50% of pts will have good control with one drug (most will have good control with 2 drugs)

poly therapy required for pts with drug resistant epilepsy

QOL monitoring for seizure disorders

seizure freq
functional status (evaluation of ability to continue employment school)
Social functioning (drivers license)
Cognition- Many antiseizure medications can have cognitive side effects
Mental health status- depression is a common co morbidity
Number of doses per day
cost of drug therapy

is seizure treatment life long?

Not necessarily. medication can be withdrawn after seizure free period of 2-5 yearsRisk

factors for seizure recurrence

Less than 2 years seizure free onset of seizure after 12 years old History of atypical febrile seizures significant number of seizures before control is achieved partial seizures (most common type) Abnormal EEG through tx organic neurologic disorder (traumatic brain injury, dementia) withdrawal of phenytoin or valproate

What is drug resistant epilepsy defined as

Defined as a failure of atleast 2 trials of antiseizure medications of adequate dose strength

Possible reasons for epilepsy tx failure

Failure to reach CNS target ALteration of drug targets in CNS Drug missing the real target

Management of drug resistant therapy

Rule out pseudoresistance- wrong drug or diagnosis combination therapy electrical/surgical intervention

Define status epilepticus

defined as continous seizure lasting 5 minutes or more or two or more discrete seizures with incomplete recovery between seizures

drug used in status epilepticus

IV drug therapy Benzodiazepine is 1st line (most commonly lorazepam and midazolam)

step by step status epilepticus tx

0-5 mins (stabilization phase) -time seizure -start ECG/O2 - check antiseizure medications serum levels and electrolytes -if BG low tx with D25/50 5-20 mins (initial tx phase) - If seizures continue- IV lorazepam or IV midazolam 20-40 (2nd tx phase) - if seizure continues, IV phenytoin, IV valproic acid, IV levetiracetam -May use phenobarbital if no access to above meds Third phase (40-60 mins) - o Clear Evidence-Based Choice [Level U] *Repeat second-line therapy *Anesthetic doses of the following PLUS continuous EEG monitoring: *Thiopental *Midazolam *Phenobarbital *Propofol

Phenytoin/fosphenytoin loading doses. What to monitor? Notable things about drugs?

Phenytoin- contains propylene glycol, so hypotension limits infusion rate 20 mg/kg IV may give additional dose 10 mins after load fosphenytoin- prodrug of phenytoin. Better IV tolerance 20 mg PE (phenytoin equivalents)/kg IV. May give additional dose 10 mins after load. monitor for cardiac symptoms. May cause local rxn called purple glove syndrome

Oral phenytoin dosing considerations

To calculate new oral dose we MUST obtain both phenytoin serum concentration and serum albumin in same blood draw.

Therapeutic serum concentration range for phenytoin

10-20 mcg/ml

Valproate loading dose, conversion, desired serum concentration.

loading dose- 15-30 mg/kg IV dosed every 6 hours IV to PO conversion is 1:1 mg/kg desired serum concentration- 80 mcg/ml (50-125)

CYP 1 A2 inducer drugs

Carbamezapines phenobarbital phenytoin (same as (2C9))

CYP2C9 inducers

Carbamezapines phenobarbitals phenytoin Same as ((2C9))

CYP3A4 inducers

Carbamezapines phenobarbital phenytoin topiramate oxcarbamezapine lamotrigine

lamotrigine boxed warning

steven johnson syndrome/toxic epidermal necrolysis

know lamotrigine dosing with UGT inhibitor, UGT inducer and without concomitant UGT interactions. Know drug names of UGT inducers and UGT inhibitors

UGT inducers- carbamezapine, phenytoin UGT inhibitors- valproate without UGT therapy 25 mg QD x 14 days 50 mg QD x 14 days 100 mg QD x 7 days 200 mg QD with UGT inhibitor(valproate) 25 mg every other day x 14 days 25 mg QD x 14 days 50 mg QD x 7 days 100 mg QD with UGT inducer (carbamezapine, phenytoin) 50 mg QD x 14 days 100 mg QD x 14 days 200 mg QD x 7 days 400 mg QD

which allele is associated with steven johnsons syndrome with initiation of carbamezapines or the like. WHat does this lead to

HLA-B *1502. We need to test for this in patients initiating therapy. If pt test positive for this allele carbamezapines or the like should not be initiated.

What other gene confers similar risk of HLA-B*1502? what populations is it risky in?

HLA-A*3101 in northern european and asian descent

Strong correlation for positive HLA-B*1502 allele and AHS in patients of Asian descent t/F

true

What is DRESS syndrome? mortality? when does it occur? What drugs is it associated with? What gene/group of people is it most related to?

Drug rxn with eosinophillia and systemic symptoms. Rash leading to multi organ failure potentially life threatening- 10% mortality occurs 2-6 wks after initiating therapy associated with carbamezapine, cenobamate, lamotrigine, phenobarbital, phenytoin, valproate, zonisamide increased risk in HLA 3101 allele (asian and northern european)