Pharmacotherapy Alzheimer Dr. Thomason Flashcards

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1
Q

Which proteins are known to be involved in Alzheimer’s disease?

A

Chromosome 1 and 14
membrane proteins:
-Presenilin 1
-Presenilin 2

-> involved in amyloid precursor protein

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2
Q

Which apolipoprotein E (APOE) genotype is associated with late onset Alzheimer’s disease?

A

APOE*4

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3
Q

Factors that increase the risk for Alzheimer’s disease

A

-Age
-head injury/trauma
-severe depression
-down syndrome
-encephalitis from herpes simplex
-vascular disease

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4
Q

How is Alzheimer’s disease daignosed?

A

autopsy for 100% confirmation
-plaque detection methods
-CTI, MRI, PET scans (tau and amyloid plaques)

-Serology: CBC (infection), CMP (electrolytes, liver dysfunction), thyroids (hypothyroidism - dementia symptoms), syphilis, vitamin b12
-check meds if they are the cause of Alzheimer-like symptoms

-EEG, neuropsychological tests (optional)

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5
Q

Drug classes indicated for Alzheimer’s disease

A

loss of cholinergic neurons is the issue

-Cholinesterase inhibitors (preserve ACh)
Donepezil (Aricept)
Rivastigmine (Exelon)
Galantamine (Razadyne)

-NMDA receptors
Memantine (Namenda)

-Amyloid monoclonal AB
Lecanamab-irmb
Donanemab

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6
Q

treatment plan

A

-mild to moderate ->
Cholinesterase inhibitors (preserve ACh)
Donepezil (Aricept)
Rivastigmine (Exelon)
Galantamine (Razadyn9

titrate up to maintenance dose due to GI side effects (nausea, diarrhea)

moderate to severe:
consider adding NMDA antagonist (memantine) -> titrate up OR monotherapy with ACh esterase or memantine

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7
Q

What to consider about memantine?

A

It doesnt work with mild to moderate Alzheimer

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8
Q

How does the Mini-Mental-Status exam progress in the process of the disease

A

if untreated it goes down by 2-4 points every year

if treated well: the decline is at less than 2

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9
Q

How do Anti-amyloid mabs work?

A

Binding to amyloid beta and preventing them from crossing the BBB

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10
Q

What is required for Lecanemab treatment?

A

treatment of MCI (mild cognitive impairment) and mild dementia -> early stage of Alzheimer’s!!!

IV every 2 months
extensive infrastructure
->PET facilities
->Labs for CSF biomarkers
->Genotype counseling

Dont give to patients on anticoagulants due to risk of hemorrhage in the brain (ARIA)

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11
Q

Which anti-amyloid requires confirmed amyloid beta pathology?

A

Donanemab (Kisunla)

confirm through MRI
-consider stopping if amyloid plaques reduces
-obtain MRI prior to 2nd, 3rd, 4th and 7th infusion, to check for hemorrhage

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12
Q

How do Cholesterase inhibitors work?

A

reversibly inhibiting hydrolysis of ACh (to acetyl and choline)
by blocking the ACh esterase

ADE: GI -> N/V, diarrhea
-> titrate up
other ADE:
Urinary retention, syncope, bradykadia?, salivation, sweating

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13
Q

Donezepil dose, ADE, counsel

A

Donezepil (Aricept)
Starting dose = 5 mg -> can titrate to 10 mg
ADE: GI
-> take it with food (some may take it without food)

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14
Q

Rivastigmine dose, ADE, counsel

A

brand name: Exelon
mostly the patch is used
starting dose: 1.5 mg BID
maintenance: 3-6 mg BID
take with a meal to decrease

MOA: reversible inhibition of ACh and butrylcholinesterase

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15
Q

Which ACh esterase inhibitors also treat anxiety and hallucinations?

A

Galantamine (Razadyne)
-> it also modulates serotonin, glutamate and GABA

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16
Q

Early VS Later treatment

A

according to studies
start later with ACh esterase inhibitor in those with severe AD

when started earlier: more functional levels were maintained, preserving quality of life
EARLIER is more often seen in clinical setting

17
Q

Which drug should be avoided in long-term AD treatment

A

Benzodiazepines
some data indicates that it is linked with cognition impairment and dementia

-sometimes used: Mood stabilizers (Gabapentin, Depakote, carbamazepine)

18
Q

Which drugs are used for Depression in AD?

A

-are not so effective but still used

-SSRIs: citalopram, escitalopram, sertraline
-Trazodone for insomnia

19
Q

Which AD drugs require tapering when D/C

A

ACh

stopping abruptly may cuase behaviral and cognitive decline
-consider reducing from 10 mg to 4 mg daily for 1 month before D/C