Pharmacotherapy Alzheimer Dr. Thomason Flashcards
Which proteins are known to be involved in Alzheimer’s disease?
Chromosome 1 and 14
membrane proteins:
-Presenilin 1
-Presenilin 2
-> involved in amyloid precursor protein
Which apolipoprotein E (APOE) genotype is associated with late onset Alzheimer’s disease?
APOE*4
Factors that increase the risk for Alzheimer’s disease
-Age
-head injury/trauma
-severe depression
-down syndrome
-encephalitis from herpes simplex
-vascular disease
How is Alzheimer’s disease daignosed?
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)
Drug classes indicated for Alzheimer’s disease
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
treatment plan
-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
What to consider about memantine?
It doesnt work with mild to moderate Alzheimer
How does the Mini-Mental-Status exam progress in the process of the disease
if untreated it goes down by 2-4 points every year
if treated well: the decline is at less than 2
How do Anti-amyloid mabs work?
Binding to amyloid beta and preventing them from crossing the BBB
What is required for Lecanemab treatment?
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)
Which anti-amyloid requires confirmed amyloid beta pathology?
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
How do Cholesterase inhibitors work?
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
Donezepil dose, ADE, counsel
Donezepil (Aricept)
Starting dose = 5 mg -> can titrate to 10 mg
ADE: GI
-> take it with food (some may take it without food)
Rivastigmine dose, ADE, counsel
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
Which ACh esterase inhibitors also treat anxiety and hallucinations?
Galantamine (Razadyne)
-> it also modulates serotonin, glutamate and GABA
