Alzheimer Flashcards
alzheimers disease
-MC form of dementia
-5.2 million Americans dx with AD
-5 million persons > age 65
-200,000 people < 65
->14 million Americans will have AD by 2050
risk factors
-Age- ~1/2 of individuals > 85 have probable AD
-Gender: Female > male (bc females live longer)
-Family history of AD- not really
-Genetic predisposition -> Apo E4
-Caucasian
-Down Syndrome
AD patho
-Excessive deposition of beta-amyloid fibrils
-“Cholinergic hypothesis”
-Decrease in activity of choline acetyltransferase
-Degeneration of cholinergic neurons
-Fewer presynaptic cholinergic receptors
-Excessive NMDA glutamate activation -> neurodegredation
course of AD
-Progressive
-Degenerative
-More than loss of memory:
-Loss of cognitive function
-Decline in ability to perform ADLs
-Change in personality and behavior- depression
-Eventual nursing home placement
10 warning signs of AD
-Memory loss
-Difficulty performing familiar tasks
-Problems w/ language
-Poor/Decreased Judgment- manic behavior
-Disorientation to time and place
-Problems w/ abstract thinking
-Misplacing things- getting keys in the fridge
-Change in mood or behavior
-Change in personality
-Loss of Initiative
stages of AD
-Mild Cognitive Impairment (MCI)
-Mild (MMSE 21-30)
-Moderate (MMSE 10-20)
-Severe (MMSE < 10)
AD often overlooked
-38% correctly diagnosed at initial physician visit
-60% are misdiagnosed!
-11% – no diagnosis
-19.5% – “usual aging” diagnosis
-8.7% – depression diagnosis
-7.4% – dementia diagnosis
drug induced cognitive impairment
-Anticholinergics
-Antihistamines
-Sedative/hypnotics
-Narcotics
-Corticosteroids
-Antiparkinson drugs
-Skeletal muscle relaxants
-Anticonvulsants
-Antipsychotics
-Antiemetics
-Antidepressants
-Alpha 2 agonists
-Disopyramide
-Lithium
-indomethacin
other drugs with anticholinergic properties
-Cimetidine!!
-Prednisolone
-Theophylline
-Digoxin
-Nifedipine
-Furosemide
-Isosorbide
-Warfarin
-Dipyridamole
-Codeine
-Triamterene/HCTZ
-Captopril
treatment
-No known cure for AD
-Acetylcholinesterase inhibitors (AChEIs) are mainstay of treatment
-Memantine – newer agent being used
-Potential Benefits with DHEA, anti-oxidants, anti-inflammatory agents (statins!), hormonal agents, statins, and vitamins
-Tx of behavioral symptoms w/ appropriate psychotherapeutic medications (CBT)
-Early stages of AD: irritability, anxiety, depression
-Late stages of AD: sleep disturbances, delusions, agitation
AChEIs
-MOA: Prevent breakdown of acetylcholine by blocking enzyme Acetylcholinesterase
-Important for memory, thought, and judgment
-takes 3-6 months to work
-Indications Used for mild-moderate AD. They are NOT recommended for mild cognitive impairment or early AD. Donepezil (Aricept) also FDA-approved for SEVERE Alzheimer’s.
-Precautions: PUD, unstable asthma or COPD!, cardiac conduction abnormalities (heart block, sinus bradycardia), concurrent digoxin, or beta-blocker use
-COPD- bc causes bronchospasm
AChEIs: ADRs and DDI
-ADRs: Generally well tolerated: MC ADRs include GI effects!, CNS effects (headache), CVS effects (bradycardia!), bronchospasm, cholinergic effects
-DDIs:
-Cholinergic drugs will exacerbate ADRs
-Anticholinergic drugs may decrease effectiveness
-Donepezil and Galantamine are CYP450 substrates
-Monitoring Parameters:
-For ADRs – esp GI effects, bradycardia, urinary incontinence
-every month monitor
-concern for wt loss with GI effects
-MMSE or other assessment tool/rating scale -> draw a clock
AChEIs: agents in this class
-Tacrine (Cognex)- LFTs SE ARE BAD! -> dont use
-Donepezil (Aricept): 5 mg, 10mg, 23 mg
-Rivastigmine (Exelon – also available as a patch)- tablet burden
-Galantamine (Razadyne)
reasonable expectations of AChEI therapy
-Improve, maintain, or slow decline in ADLs and cognitive function
-Control or delay emergence of troublesome behaviors
-Ease patient’s loss of independence
-Ease caregiver burden
-Delay placement in long-term care facility
-All AD pts eventually deteriorate over time
cholinesterase inhibitors: comparative pharm, pharmokinetics, and dosing
-donepezil is used to start -> very long half life (70hrs)
-DO NOT MEMORIZE ANYTHING ELSE
cholinesterase inhibitors: comparative pharm, pharmokinetics, and dosing
cont.
-DONEPEZIL has CYP450 drug interactions -> if the pt is having issues -> switch to rivastigmine
-best for GI is donepezil
-worst for GI is rivastigmine
-increase dose slow
-NOTHING ELSE ON TEST
memantine
-MOA – NMDA antagonist. Excessive NMDA plays a role in pathophysiology of AD
-Precaution – renal dysfunction
-Used in moderate to severe AD
-Can combine w/ AChEIs
-ADRs - dizziness, headache, confusion, constipation or diarrhea
-DDIs – no CYP450 DDI, no cholinergic/anticholinergic DDIs
combo product: memantine + donepezil
-decrease pill burden but $
-NMDA antagonist + cholinesterase inhibitor
-Use in moderate to severe AD.
-Blocks effects associated with excess glutamate, prevents breakdown of acetylcholine in the brain
-ADR: HA, N/V, diarrhea, dizziness, anorexia
amyloid beta-directed antibody: aducanumab
-DISCONTINUED
-under accelerated approval pathway
-provides pts with serious disease earlier access to drugs when there is expected clinical benefit despite some uncertainty aboutclinical benefit
-$$$
-1st therapy to demonstrate that removing beta-amyloid, from brain is likely to reduce cognitive and functional decline in people living with early Alzheimer’s
other tx options
-Cholinergic Receptor Agonists – Bethanechol- this is an old tx
-NSAIDS - May reduce inflammation that contributes to the plaque formation of AD -> not a huge help, GI effects
-Statins – 2 studies showing possible relationship b/w statins and decrease AD -> Need more studies -> Yet other studies show cognitive impairment w/ statins!
-Hormonal Therapy: DHEA
-Vitamins: Folic acid, B6, B12, Vit E, Vit C
natural medicines: AChEIs/NMDA inhibitor
Huperzine A (Memorall, MindPro, Memory Mate) - use in combo with donezipil not in leu of
-Acetylcholine Precursors: Acetyl-L-carnitine, Choline, Lechitin, Phosphatidylcholine
-Antioxidants: Ginkgo, Vit E, Vit C, beta-carotene
-Anti-inflammatory agents: Cat’s claw, Ginkgo (can cause bleeding and DDI), Gotu kala
medical food: axona
Powder product that provides ketones as an alternative fuel source for the brain. GI side effects are common
JL, a 62 year old female with a past medical history of HTN comes to your office with her daughter. Her daughter informs you that her mother is experiencing short term memory loss, confusion, constantly loses thing, dresses inappropriately and can’t do the simple things she used to. Current medications include:
HCTZ 25mg PO daily
Enalapril 20mg PO daily
Cimetidine 75 mg PO PRN for acid indigestion
Diphenhydramine 25mg PO QHS PRN sleep
-What is your initial diagnosis?- alzheimers
-What diagnostic exam would you perform at this time?
-MMSE
-switch her to a PPI and start Donepezil
-Write a prescription and provide education
beta-amyloid directed antibody
-Donanemab-azbt
-approved for early ds
-NOT ON TEST?- SLIDES ADDED ON
