Week 2 Flashcards
1
Q
Dementia
A
- Progressive decline of intellectual ability from a previously attained level (baseline)
- Deterioration of speech, memory, judgement and mood
2
Q
1 Risk Factor for Alzheimer’s/Dementia
A
Age
3
Q
Most common forms of Dementia
A
- Alzheimer’s (70%)
- Over 85 years; Both Alzheimer’s and Vascular Dementia
4
Q
Vascular Dementia
A
- 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
5
Q
Alzheimer’s Disease
A
- Progressive, neurodegenerative disorder affecting cognition and behavior
- Slow decline over time (not stepwise)
- **Impairment in activities of daily living
6
Q
Warning signs for Alzheimer’s
A
- 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
7
Q
Apolipoprotein E4 (APOE4)
A
Factor associated with family risk of Alzheimer’s (not well understood)
8
Q
Mild Cognitive Impairment (MCI)
A
Impaired cognition, memory or behavior WITHOUT impairment of daily activities
9
Q
Mini-Mental Status Scores (not sure if we need to know)
A
> 26 - Normal
20-26 - Mild Dementia
12-20 - Moderate Dementia
<12 - Severe Dementia
10
Q
Alternative sources to cognitive impairment
A
- B12 deficiency
- Normal Pressure Hydrocephalus (NPH)
- Hypothyroidism
- Infections (HIV, UTIs in elderly)
- Anticholinergics in elderly
- Alcoholism/Chronic drug intoxication
11
Q
Areas of brain involved in Alzheimer’s
A
- Cerebral cortex (atrophy/shrinks)
- Hippocampus (converts short term memories to long term)
- Amygdala
12
Q
Anticholinergics associated with Alzheimer’s in the elderly
A
- Antihistamines (Doxylamine, Benadryl)
- **Cimetidine (#1 OTC)
- TCAs (Amitriptyline, Cyclobenzaprine)
- Bladder Meds (Oxybutynin)
- Antiemetics (Meclizine, Scopolamine, Prochlorperazine)
- Antipsychotics (Clozapine, Chlorpromazine, Thioridazine)
- Codeine
13
Q
What is concern for Anticholinergics with elderly in Alzheimer’s?
A
- 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
14
Q
Non-pharm therapies for ALZ
A
- 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.)
15
Q
Medication classes for memory
A
- Acetylcholinesterase inhibitors
- Memantine
- Anti-amyloid agents
16
Q
Treatments for behavior
A
- Non-pharm therapies 1st line
- Antidepressants/anxiety/psychotics (*Black box warning for antipsychotics : increased mortality in dementia elderly pts)
17
Q
Donepezil (Aricept)
A
- 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
18
Q
Donepezil ADEs
A
- Bradycardia
- Rhabdomyolysis and/or neuroleptic malignant syndrome (v. rare)
- Less GI effects but more sleep disturbances than other drugs in class
19
Q
Rivastigmine (Exelon)
A
- 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
20
Q
Rivastigmine ADEs
A
- Tabs: GI issues (require slow titration, take with food)
- Patch: site reactions (less GI vs tabs)
21
Q
Galantamine (Razadyne)
A
- 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
22
Q
Memantine (Namenda)
A
- 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)
23
Q
Memantine Precautions
A
- History of seizure disorder (increased risk of seizures)
- Cardiovascular disease (increased incidence of cardiac failure, angina, bradycardia and HTN)
24
Q
Memantine ADEs
A
- Dizziness
- Constipation (AChEi cause diarrhea, may help offset if on both together)
- Issues with balance
25
Hallmark Pathology signs of AD in the brain
1. Beta-amyloid plaques (disrupts neurons, affects hippocampus and cerebral cortex)
2. Neurofibrillary tangles (tau destabilizes leading to microtubule collapse and cell structure failure)
26
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
27
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
28
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
29
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
30
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
31
What are TIAs
- Visual loss
- Abrupt
- Simultaneous occurrence
- Duration < 15 minutes
- Headache is an uncommon accompaniment
32
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
33
Options for mild-moderate migraine attacks
- NSAIDs
- Acetaminophen
- Caffeinated analgesic combinations (non-opiate!)
34
Options for moderate-severe migraine attacks or refractory mild-moderate migraine attacks
- Triptans
- DHE
- Gepants/ditans (if triptans are not tolerated/contraindicated)
35
NSAID options
Diclofenac potassium oral solution
- Powder form - mix in 2-4 TBSP of water
Celecoxib oral solution
Can be used in adults with/without aura
36
Butalbital/Caffeine/APAP
- BBW for hepatoxicity
- Non-controlled
- Indicated for tension HA, but used for migraines
- 50 mg butalbital, 300-325 mg APAP, 40 mg caffeine
- AE: CNS depression, stomach upset
- Common for medication overuse headache
37
Butalbital/Caffeine/ASA
- CIII
- Indicated for tension HA, but used for migraines
- 50 mg butalbital, 325 mg ASA, 40 mg caffeine
- AE: CNS depression, stomach upset
- Common for medication overuse headache
38
Triptans
- Administer early in the course of a migraine attack to improve treatment response
- AE: flushing, chest pain, palpitations, dizziness, fatigue, xerostomia, serotonin syndrome
- Limit use to less than 10 days per month (medication overuse headache)
- Caution in older adults
- May combine with NSAIDs
39
Triptan CIs
- Hemiplegic migraine or migraine with brainstem aura
- Known/suspected ischemic heart disease/ CV disease
- Wolff-Parkinson-White syndrome or arrhythmias
- Stroke, TIA
- Peripheral vascular disease (including ischemic bowel disease)
- Uncontrolled hypertension
- Use within 24 hours of an ergotamine preparation or other triptan
- MAOIs (with riza, suma, and zolmi)
40
Triptans with the longest half life?
Frovatriptan (26 hours)
Naratriptan (6 hours)
41
Triptan CI with potent 3A4 inhibitors
Eletriptan
42
Triptan with an SQ, PO, and Intranasal route of admin
Sumatriptan
43
Triptan with a PO and intranasal route of admin
Zolmitriptan
44
Triptan with the quickest onset of action
Sumatriptan SQ (10 mins!)
Then sumatriptan intranasal (15-30 minutes)
45
Lasmitidan (Reyvow)
- CV
- Max of one dose per day
- Use not recommended in severe hepatic impairment
- Must wait at least 8 hours between dosing and operating heavy machinery or driving
AE: CNS depression, serotonin syndrome, decreased HR, increased BP, palpitations, dizziness, nausea, vomiting
46
Rimegepant (Nurtec)
- PO ODT
- Acute AND preventative treatment for migraine
- Prevention dose is every other day
- Avoid use in severe hepatic impairment and CrCl < 15 mL/min
- Onset of action < 2 hours
- AE: abdominal pain, dyspepsia, nausea
47
Ubrogepant (Ubrevly)
- PO tablet
- Acute treatment in adults with/without aura
- Can repeat a dose after 2 hours
- Contraindicated with strong 3A4 inhibitors
- Dose reduction CrCl <30 mL/min, avoid < 15 mL/min
- Dose reduction with severe hepatic impairment
AE: nausea, drowsiness, xerostomia
48
Anti-migraine ergots
- BBW: contraindicated with potent CYP3A4 inhibitors, including protease inhibitors, macrolide antibiotics, and azole fungals
- AE: Cardiac valvular fibrosis, ergotism, serotonin syndrome
- Do not use in pregnancy or breastfeeding
- Do not use within 24 hours of triptans, other serotonin agonists, or ergotamine-containing or ergot-like agents
-Monitoring: renal and liver function, cardiovascular status
49
Ergotamine
- Not recommended in older adults
- AE: nausea, vomiting, ECG changes, hypertension, ischemia, vasospasm, numbness, paresthesia, gangrene
- D/C may result in withdrawal symptoms, such as rebound headache
- Interaction with grapefruit juice (increased levels)
- May worsen nausea/vomiting with headache
50
Dihydroergotamine
- Injection: cluster headaches and migraine
- NS: migraine
- Fewer side effects than ergotamine
- CI: ischemic heart disease, coronary artery vasospasm, following vascular surgery, concurrent use of peripheral and central vasoconstrictors, NS is contraindicated with brainstem aura or hemiplegic migraine
- Do not use within 24 hours of another ergotamine or triptan
- Monitoring: CAD risk factors, cardiovascular evaluation
51
Severe migraine treatment in the ED
IV/IM dexamethasone
SQ sumatriptan
IV prochlorperazine + diphenhydramine
IV metoclopramide + diphenhydramine
IV chlorpromazine + diphenhydramine
IV DHE + antiemetic
IV valproate
IV/IM ketorolac
IV magnesium
52
When to give preventative migraine treatment
- Attacks significantly interfere with patient's daily routines despite acute treatment
- Frequent attacks
- Contraindication to, failure, or overuse of acute treatments
- AEs with acute treatments
- Patient preference
53
Topiramate
- Prevention of migraine
- AE: cognitive dysfunction, CNS effects, nephrolithiasis, metabolic acidosis, angle-closure glaucoma, oligohidrosis/hyperthermia, suicidal ideation, weight loss, paresthesia
- Counsel on importance of hydration
- Avoid in pregnancy
54
Valproic acid
- BBW: hepatotoxicity, patients with mitochondrial disease, fetal risk, pancreatitis
- Migraine prevention
- AE: CNS effects, hepatotoxicity, encephalopathy, TEN, SJS, DRESS, pancreatitis, suicidal ideation
- CIs: Prevention of migraine in pregnant women and women of childbearing potential who are not using effective contraception, severe hepatic impairment, mitochondrial DNA polymerase gamma mutation-associated mitochondrial disorders
55
Beta-Blockers
Propranolol, timolol are indicated for prevention of migraine
56
Tricyclic antidepressants
Amitriptyline, nortriptyline
- BBW: suicidality
- Lower initial doses for migraine prevention than for MDD
AE: anticholinergic effects, CNS depression, cardiac conduction abnormalities, orthostatic hypotension, serotonin syndrome
57
Venlafaxine
- BBW: suicidality
- AE: CNS depression, weight loss, anorexia, increased blood pressure, hepatotoxicity, hyponatremia, acute angle-closure glaucoma, serotonin syndrome
58
Atogepant (Qulipta)
- Preventative treatment of episodic migraine in adults
- Once daily doses
- Not recommended for use in severe hepatic impairment
- Dose reduction CrCl < 30 mL/min
AE: constipation, nausea, drowsiness, fatigue, weight loss
59
CGRP monoclonal antibodies
Caution in patients with recent cardiovascular or cerebrovascular ischemic events
60
Eptinezumab (Vyepti)
- CGRP ligand
- IV Q3M
- AE: infusion reactions, nasopharyngitis, nausea
61
Erenumab (Aimovig)
- CGRP receptor
- SQ QM
- AE: injection site reactions, constipation
62
Fremanezumab (Ajovy)
- CGRP ligand
- SQ QM or Q3M
- AE: injection site reaction
63
Galcanezumab (Emgality)
- CGRP ligand
- SQ QM
- AE: Injection site reaction
64
Peripheral nerve blocks
Use lidocaine and/or bupivacaine and/or methylprednisolone
65
Non-pharm treatments for migraine
Stress reduction techniques
Dietary changes
Trigger avoidance
Magnesium
Vitamin B2
Feverfew
Butterbur
Neuromodulation devices
66
PO Magesium
- Migraine prophylaxis
- AE: diarrhea, N/V
67
Vitamin B2
- Migraine prophylaxis
68
Feverfew
- Migraine prophylaxis
- Avoid use in pregnancy
AE: GI (stomach pain, bloating, constipation, diarrhea, flatulence, heartburn, nausea)
69
Butterbur
- Migraine prophylaxis
- Avoid products that are not labeled as free from Pyrrolizidine alkaloids
- AE: GI (belching, diarrhea, stomach upset), drowsiness, fatigue, pruritis, rash, hepatotoxicity
70
Botox
- Neurotoxin that prevents calcium-dependent release of ACh and produces a state of denervation
- BBW: spread of toxin effect
- Indicated for prevention of chronic migraine headaches in adults (>15 days per month with headache lasting > 4 hours per day)
- Administered Q12W
- AE: injection site pain, neck pain, myalgia, facial paresis
71
Menstrual migraines
- Frovatriptan x 6 days
- Naratriptan X 5-6 days
- Zolmitriptan x 7 days
- Magnesium
- Acute treatments
- COC (avoid with patients with aura)
72
Special Populations
Acute migraine treatment for patients with cardiovascular/cerebrovascular disease: gepants and lasmiditain
Acute migraine treatment for pregnant patients: APAP
73
Tension Headaches
- 30 mins to 7 days in duration
- Bilateral, pressing/tightening, mild-moderate intensity, not aggravated by physical activity
- No N/V
- NMT 1 of photophobia/phonophobia
74
Tension headache therapies
- Simple analgesics (NSAIDs, APAP)
- Analgesics comboed with caffeine
- Last line: Combo analgesics with butalbital or codeine (counsel on medication overuse headache)
Preventative: Antidepressants, anticonvulsants, trigger point injections
75
Cluster headache treatment
Acute: oxygen, SQ or intranasal sumatriptan, intranasal zolmitriptan
Preventative: Verapamil (preferred!), glucocorticoids, galcanezumab, lithium, topiramate, greater occipital nerve blocks
76
Hemicrania continua treatment
Indomethacin (preferred!) , Botox, occipital nerve stimulation, vagus nerve stimulation, peripheral nerve blocks
77
Pseudotumor cerebri treatment
Withdraw offending agent
Weight loss
Carbonic anhydrase inhibitors (acetazolamide, topiramate)
Furosemide
Migraine preventive medications
78
Medications associated with reversible cerebral vasoconstriction syndrome
SSRIs
Triptans
Ergots
Cyclophosphamide
Tacrolimus
Nasal decongestants
Illegal drugs
Others
79
Symptoms of subarachnoid hemorrhage (life threatening emergency!)
Sudden or thunderclap onset of headache
Worst headache of their life
N/V
Photophobia
Neck stiffness
Focal neurologic deficits
Brief loss of consciousness
80
Medication overuse headache causes
> 5 days per month: butalbital
> 10 days per month: triptans, opioids, anti-migraine ergots
> 15 days per month: non-opioid analgesics
Wean off or D/C, use bridge therapy, or initiate preventative and breakthrough therapy
81
Substance withdrawal headache
Caffeine > 200mg/day for > 2 weeks
Opioids > 3 months
