Week 2 Flashcards
Dementia
- Progressive decline of intellectual ability from a previously attained level (baseline)
- Deterioration of speech, memory, judgement and mood
1 Risk Factor for Alzheimer’s/Dementia
Age
Most common forms of Dementia
- Alzheimer’s (70%)
- Over 85 years; Both Alzheimer’s and Vascular Dementia
Vascular Dementia
- Impaired cognition due to multiple ischemic events to the brain (strokes)
- May present from sub-clinical strokes (lacunar)
- **Involves stepwise decline
- African Americans, Japanese, elderly with comorbidities at higher risk
Alzheimer’s Disease
- Progressive, neurodegenerative disorder affecting cognition and behavior
- Slow decline over time (not stepwise)
- **Impairment in activities of daily living
Warning signs for Alzheimer’s
- Problems with words/speaking
- Poor judgement
- Withdrawal from social/work life
- Changes in mood/personality
- Memory loss that disrupts daily life
- Problems with visual and spatial relationships
Apolipoprotein E4 (APOE4)
Factor associated with family risk of Alzheimer’s (not well understood)
Mild Cognitive Impairment (MCI)
Impaired cognition, memory or behavior WITHOUT impairment of daily activities
Mini-Mental Status Scores (not sure if we need to know)
> 26 - Normal
20-26 - Mild Dementia
12-20 - Moderate Dementia
<12 - Severe Dementia
Alternative sources to cognitive impairment
- B12 deficiency
- Normal Pressure Hydrocephalus (NPH)
- Hypothyroidism
- Infections (HIV, UTIs in elderly)
- Anticholinergics in elderly
- Alcoholism/Chronic drug intoxication
Areas of brain involved in Alzheimer’s
- Cerebral cortex (atrophy/shrinks)
- Hippocampus (converts short term memories to long term)
- Amygdala
Anticholinergics associated with Alzheimer’s in the elderly
- Antihistamines (Doxylamine, Benadryl)
- **Cimetidine (#1 OTC)
- TCAs (Amitriptyline, Cyclobenzaprine)
- Bladder Meds (Oxybutynin)
- Antiemetics (Meclizine, Scopolamine, Prochlorperazine)
- Antipsychotics (Clozapine, Chlorpromazine, Thioridazine)
- Codeine
What is concern for Anticholinergics with elderly in Alzheimer’s?
- Marked decrease in ACh in ALZ pts
- ACh plays role in memory formation
- Exposure to anticholinergics 10 years prior to dementia diagnosis associated with dementia AND risk does NOT go away when drug is D/C’d
Non-pharm therapies for ALZ
- Memory books/notes
- Environmental changes (quiet, well-lit rooms)
- Exercise/ Occupational therapy
- Cognitive Rehab (early stages only)
- Support groups
- Pt input on health choices prior to loss of judgement (power of attorney, proxy, will, etc.)
Medication classes for memory
- Acetylcholinesterase inhibitors
- Memantine
- Anti-amyloid agents
Treatments for behavior
- Non-pharm therapies 1st line
- Antidepressants/anxiety/psychotics (*Black box warning for antipsychotics : increased mortality in dementia elderly pts)
Donepezil (Aricept)
- AChE inhibitor
- Indicated for mild to severe AD
- 5 mg daily for 4-6 weeks (can inc to 10mg or 23mg if desired)
- CYP2D6/3A4 metabolite
Donepezil ADEs
- Bradycardia
- Rhabdomyolysis and/or neuroleptic malignant syndrome (v. rare)
- Less GI effects but more sleep disturbances than other drugs in class
Rivastigmine (Exelon)
- AChE inhibitor
- Indicated for mild to severe AD and mild to moderate Parkinson’s dementia
- NOT metabolized by CYP (only AChEi)
- Tabs: 6-12 mg/day given BID
- Patch: 4.6mg/day for 4 weeks (increase to 9.5mg if tolerated)
- Patch should ONLY be applied to back, arms and chest for best absorption
Rivastigmine ADEs
- Tabs: GI issues (require slow titration, take with food)
- Patch: site reactions (less GI vs tabs)
Galantamine (Razadyne)
- AChE inhibitor
- Indicated for mild to moderate AD
- IR: 4mg BID for 4 weeks (inc to 8,12)
- ER: 8mg daily for 4 weeks (inc to 16, 24)
- Should NOT be used in hepatic/renal failure
- CYP2D6/3A4 metabolite
Memantine (Namenda)
- NMDA receptor antagonist
- Approved for moderate to severe AD
- Not metabolized by CYP enzymes
- **CL significantly reduced by alkaline urine (caution with meds/diet in urine pH)
- IR: 5mg daily (target dose 20mg)
- ER: 7mg daily (target dose 28mg)
Memantine Precautions
- History of seizure disorder (increased risk of seizures)
- Cardiovascular disease (increased incidence of cardiac failure, angina, bradycardia and HTN)
Memantine ADEs
- Dizziness
- Constipation (AChEi cause diarrhea, may help offset if on both together)
- Issues with balance
Hallmark Pathology signs of AD in the brain
- Beta-amyloid plaques (disrupts neurons, affects hippocampus and cerebral cortex)
- Neurofibrillary tangles (tau destabilizes leading to microtubule collapse and cell structure failure)
Aducanumab (Aduhelm)
- Anti-amyloid therapy (directed against aggregated soluble/insoluble amyloid beta)
- Partially FDA approved due to 1 of 2 trials showing no clinical improvement
- Indicated for MCI or mild AD
- 10 mg/kg IV infusion every 4 weeks
Anti-Amyloid Precautions/ADEs
- **Boxed warning for ARIA (Amyloid related imagining abnormalities)
- ARIA-E: vasogenic edema or sulcal effusions/exudates
- ARIA-H: microhemorrhages or hemosiderosis
Symptoms of ARIA
Usually asymptomatic but present on scan
- Headache
- Confusion/delirium/AMS
- Dizziness/vertigo
- Visual disturbances/Nausea
D/C drug therapy if moderate to severe on MRI regardless of symptoms
Lecanemab (Leqembi)
- Anti-amyloid therapy
- Received FULL FDA approval (slowed disease progression by 27% ~ 7 months)
- 10 mg/kg IV every 2 weeks
- Boxed warnings for ARIA
- ADEs: Infusion related reactions
What are migraines
At least 5 attacks with:
- Headaches lasting 4-72 hours
- Headaches that are (at least 2/4) unilateral, pulsating, moderate/severe pain intensity, are aggravated by or cause by physical activity
- During headache, have photophobia/phonophobia and/or nausea/vomiting
What are TIAs
- Visual loss
- Abrupt
- Simultaneous occurrence
- Duration < 15 minutes
- Headache is an uncommon accompaniment
Migraine pharmacotherapy principles
- Acute treatment is more effective if given early in the course of a headache
- A large single dose is better than small, repetitive doses
- Counsel patients on medication overuse headache