1
Q
What is the simplified pathophysiology of migraines? (i.e., what are the 4 steps to a migraine occurring?)
A
- Some people have sensitized neurons - unclear why
- A migraine trigger comes along
- The brain releases potent vasodilators (e.g., CGRP, nitric oxide) and inflammation reactions
- Vasodilation = big pain; inflammation begets more inflammation
2
Q
3 possible symptoms of migraine aura are?
A
- Visual aura (90% of symptoms)
- Sensory disturbances
- Speech disturbances
3
Q
Should know some migraine triggers. (10 - get 6)
A
- Stress
- Meal-skipping (consider food insecurity)
- Foods (e.g., chocolate or soft cheese)
- Alcohol (esp red wine)
- Caffeine withdrawal
- Dehydration
- Menstruation
- Lights/sunlight
- Erratic sleep/shift work
- Perfume /odor
- Obesity
- Change in barometric pressure
4
Q
Each symptom of POUND is worth one point.
How does likelihood of migraine change in the following:
0-2 points
3 points
4-5 points
A
0-2 points = 17%
3 points = 64%
4-5 points = 92%
4
Q
Know the POUND mnemonic for diagnosis of migraine
A
Pulsatile quality of headache
One-day duration of headache (4-72 hours if untreated or unsuccessfully treated)
Unilateral headache
Nausea or vomiting
Disabling intensity of headache
4
Q
What are the 5 steps of acute migraine treatment?
A
Step 1: NSAID
- Response in ~4-5/10 pts
Step 2: Triptan
- Response in ~5-6/10 pts
Step 3: NSAID + Triptan
- Response in ~6-7/10 pts
Step 4: SubQ sumatriptan
- Response in ~8/10 pts
Step 5: Refractory pts
- Try alternative combinations
- Start prophylaxis
- Possible try DHE nasal spray
5
Q
How might we manage NSAID failure? (2)
A
- Ensure NSAID is taken at the earliest onset of migraine pain and on an empty stomach (food delays onset)
- Try a faster-acting NSAID formulation (liquigel typically 10-20 minute faster onset than regular tabs)
6
Q
How might we manage triptan failure? (5)
A
- Ensure triptan is taken at the earliest onset of migraine pain
- Switch to a different triptan (try at least 3)
- Add acet, an NSAID, or metoclopramide to triptan therapy
- Ensure adequate absorption (e.g., switch to nasal or injectable if vomiting up oral dose)
- Fast-acting triptans often preferred, but if tolerability concerns may try a slow-onset triptan (i.e., naratriptan or frovatriptan)
7
Q
What are 2 medication types that should be avoided in acute migraine management?
A
- Opioids
- Barbituates
8
Q
Why should T3’s be avoided for migraines? (4)
A
- Opioids have double to risk of medication overuse headache compared to other agents
- Caffeine dose is subtherapeutic
- Acetaminophen dose is often subtherapeutic
- Codeine metabolism is unpredictable
9
Q
What are the 2 major MOAs of triptans?
A
- Potent vasoconstrictors
- Potent serotonin agonists
10
Q
What are some side effects due to vasoconstriction of triptans? (4)
A
- Can cause chest discomfort/tightness
- Palpitations
- Dizziness
- Facial flushing
11
Q
What are 2 CI’s of triptans due to vasoconstriction?
A
- CVD
- CI within 24 hours of ergots (e.g., DHE) due to additive coronary vasospasm; also do not combine triptans
12
Q
What is a side effect due to serotonin agonism of triptans?
A
Can cause nausea
13
Q
What is a CI of triptan due to serotonin agonism?
A
CI with MAOIs (risk of serotonin syndrome) and cautioned with other serotonin drugs
14
Q
Triptans have unique dosage forms. What are 2 side effects related specifically to dosage forms?
A
- Injection site reactions with injection
- Bad taste with nasal spray
15
Q
All of the triptans are fast acting except for which 2?
A
Naratriptan and Frovatriptan
16
Q
The fastest triptans and fastest dosage forms are? (2)
A
- Sumatriptan subcut and nasal. 10 and 10-15 mins respectively
- Zolmitriptan nasal 10-15 mins
17
Q
The highest efficacy triptan is?
A
Subcutaneous sumatriptan (80% of pts)
18
Q
What are 3 acute migraine tips and tricks?
A
- Try a triptan for 3 migraines before giving up, and try at least 3 triptans before giving up on the class
- Acetaminophen alone or combination can be helpful (but overall is less powerful than an NSAID)
- Nausea/vomiting is common with migraines - an orally disintegrating tablet can be useful; an antiemetic can be useful; an intranasal dosage form can be useful; injectable sumatriptan can be useful
19
Q
Orally disintegrating triptans are no faster than regular tablets, and may even be slower. Why?
A
Dissolving in the mouth but not sublingual absorption. It takes a while to get into the stomach and small intestine after it dissolves. If you take it with water it’s at least comparable to a regular tab in terms of speed
20
Q
What is the max days per month you can take the following acute medications in order to avoid medication overuse headache:
Triptans
Opioids
NSAIDs or Acetaminophen
Multiple classes
A
Triptans = 9 days
Opioids = 9 days
NSAIDs/Acet = 14 days
Multiple classes = 9 days
21
Q
For some, migraines increase during menstruation.
What are some options for pre-treatment (starting ~2 days before menstruation) (4)?
A
- Naproxen 500mg BID x 6 days
- Naratriptan 1mg BID x 6 days
- Frovatriptan 2.5mg BID x 6 days (best evidence but most expensive)
- Estradiol gel 1.5mg daily x 7 days
22
Q
What does CGRP do? What then, would anti-CGRP do?
A
CGRP is a vasodilator.
Anti-CGRP prevents vasodilation by getting rid of the CGRP
23
What are the 2 anti-CGRP medications? (-gepants) Might as well know their dose too.
1. Ubrogepant
- Treatment dose: 50-100mg stat
2. Atogepant (prevention only)
- Prevention dose: 10-60mg daily
24
What are the adverse effects of the -gepants (anti-CGRP)? (2)
1. Nausea
2. Somnolence
25
How do -gepants compare to triptans in terms of efficacy?
Likely NOT as effective as triptan for acute migraine, although not compared head-to-head
26
What is two big W's for the -gepants (anti-CGRP)?
1. Appears to have very low risk of medication overuse headache
2. Not contraindicated in CV disease
27
Migraine prophylaxis is commonly underutilized. Who should consider using it? (4)
1. Pt preference
- Pt prefers prophylaxis for any reason (e.g., based on their occupation)
2. Frequent attacks
- e.g., >6 headache days/month
3. Severely disabling attacks
- Especially if >3/month
4. Difficult-to-treat attacks
- Acute treatment doesn't work well, is contraindicated, or causes problems
28
What are the 5 steps of setting up an adequate trial of a prophylactic migraine medication?
1. Initiate a headache diary
2. Start a migraine prevention drug at a low dose
3. Increase the dose gradually, every 1-2 weeks, guided by target dose range, patient response and tolerability
4. Remain at that dose for ~8-12 weeks to assess effectiveness and tolerability
5. Assess and decide whether to continue, increase the dose, or taper/discontinue the drug
29
Which drugs and which target dose has the best efficacy data for migraine prophylaxis? (4)
1. Amitriptyline ~50-75mg/day at bedtime
2. Propranolol ~80-160mg/day
3. Metoprolol ~100-200mg/day
4. Topiramate ~100mg/day
30
Which 3 drugs (and dose) seem to have the fewest adverse effects when it comes to migraine prophylaxis?
1. Candesartan 16mg/day
2. Magnesium ~500-600mg/day
3. Riboflavin ~400mg/day
31
Migraine Prophylaxis and comorbidities:
If a smoker, try:
Nortriptyline
32
Migraine Prophylaxis and comorbidities:
If insomnia, try:
Amitriptyline
33
Migraine Prophylaxis and comorbidities:
If hypertension, try (4)
1. Beta-blocker
2. Candesartan
3. Lisinopril
4. Verapamil
34
Migraine Prophylaxis and comorbidities:
If chronic pain, try (5)
1. Amitriptyline
2. Venlafaxine
3. Duloxetine
4. Topiramate
5. Possibly gabapentin
35
Migraine Prophylaxis and comorbidities:
If depression/anxiety, try (4)
1. Venlafaxine
2. Duloxetine
3. Amitriptyline
4. Optimize the role of non-drug approaches e.g., CBT, lifestyle changes
36
For migraine prophylaxis, what is a realistic expectation to set when it comes to goals?
Decrease in migraine days per month by ≥50%; less severe headaches okay too
37
If migraine prophylaxis trial fails, consider: (3)
1. Another drug class, and/or
2. Combo therapy (drug/drug) or (drug/non-drug)
3. A CGRP antagonist, e.g., fremanezumab, if failure with 2 or more conventional agents
38
Treat at target dose for _-__ weeks before deciding if prophylaxis is helping
8-12
39
Migraine vs. Tension type vs. Cluster headache:
Compare the duration
Migraine = 4-72 hours
Tension = 30 mins to 7 days
Cluster = 15 mins to 3 hours when untreated
40
Migraine vs. Tension type vs. Cluster headache:
Compare the location
Migraine = typically unilateral (but 40% bilateral)
Tension = typically bilateral
Cluster = unilateral, orbital, supraorbital, temporal, or a combination of these
41
Migraine vs. Tension type vs. Cluster headache:
Compare the pain descriptions
Migraine = usually pulsating pain; moderate to severe intensity
Tension = usually pressing or tightness (nonpulsating) pain; mild to moderate intensity
Cluster = stabbing, nonpulsating pain; severe to excruciating intensity
42
What are the common symptoms of tension-type headaches? (3. 1 is actual side effect, 2+3 are non-side-effects)
1. Either photophobia or phonophobia are present
2. Nausea and vomiting are NOT present
3. Usually not aggravated by routine physical activity such as walking or climbing stairs
43
What are the common symptoms of cluster headaches? (2+6)
1. Occurs in clusters from every other day to up to 8 headaches per day
2. May have the following ipsilateral symptoms:
- Conjunctival injection or lacrimation
- Nasal congestion or rhinorrhea
- Eyelid edema
- Forehead and facial sweating
- Miosis or ptosis
- Restlessness or agitation
44
Acute treatment for tension-type headaches include? (5)
1. NSAIDs
2. Acet
3. IV or IM ketorolac
4. Metoclopramide
5. Chlorpromazine
45
Acute treatment for cluster headache include? (5)
1. Subcutaneous sumatriptan
2. Intranasal sumatriptan
3. Intranasal zolmitriptan
4. High-flow oxygen
5. Non-invasive vagal nerve stimulation (if episodic cluster headache)
46
What might be used as prophylaxis for tension-type headaches?
TCA (ami- or nortriptyline)
47
What might be used as prophylaxis for cluster headaches? (4)
1. Verapamil (target 240-960mg per day)
2. Lithium
3. Galcanezumab
4. Topiramate
48
What are the red flag signs and symptoms of acute headache which would make you call for an ambulance (emergency)? (6)
1. Worst headache
2. Impairment of speech, sensation, strength, or consciousness
3. Fever or neck stiffness
4. Thunderclap headache (severe peak intensity in seconds to minutes)
5. Eye symptoms
6. Head trauma
49
What are the red flag signs and symptoms of acute headache which would make you send the pt for a referral (urgent)? (6)
1. First ever headache
2. Headache with exercise or sex
3. New headache if age >50 yrs
4. HIV, cancer, lyme disease, or pregnancy
5. Papilledema
6. Older adult with cognitive changes
50
What is the critical drug interaction between propranolol and rizatriptan ("gotta give props to the rizz")? (2)
1. Propranolol slows rizatriptan metabolism and thus increases levels by ~70%
2. For any pts on propranolol, use rizatriptan 5mg tabs (and not 10mg tabs)
- Or change to a different triptan
- Or change to a different beta-blocker
51
What are the new CGRP monoclonal antibody medications? (4) (FEGE)
1. Fremanezumab
2. Erenumab
3. Galcanezumab
4. Eptimezumab
52
Why is once monthly CGRP monoclonal antibody injection preferred to Q3 months?
Once monthly keeps the Cp pretty consistent, and doesn't allow for the body to produce anti-drug antibodies. Whereas, Q3 months, the trough gets pretty low, and the body can produce those antibodies, rendering the drug useless.
53
What are 2 AEs associated with CGRP monoclonal antibodies?
1. Injection site reactions
2. HTN
54
CGRP monoclonal antibodies often work how quickly?
Days (but give 3-6 months for adequate trial)
55
What are the 3 beta-blockers that can be given for migraine prophylaxis?
1. Propranolol*
2. Metoprolol*
3. Timolol
56
What is the target dose of propranolol in migraine prophylaxis?
40-80mg BID OR
80-160mg LA daily
57
What is the target dose of metoprolol in migraine prophylaxis?
50-100mg BID OR
100-200mg SR daily
58
What are the 2 TCAs that can be used in migraine prophylaxis?
1. Amitriptyline
2. Nortriptyline
59
What is the target dose of amitriptyline in migraine prophylaxis?
50-75mg HS (100mg if tolerated)
60
What are the 2 anticonvulsant drugs that can be used in migraine prophylaxis?
1. Topiramate
2. Divalproex
61
What is the target dose of topiramate in migraine prophylaxis?
50mg BID
62
Which ACEi and ARB can be used for migraine prophylaxis?
1. Lisinopril
2. Candesartan
63
What is the target dose of candesartan for migraine prophylaxis?
16mg daily
64
What are the SNRIs that can be used in migraine prophylaxis? (2)
1. Venlafaxine
2. Duloxetine
65
What are the CCBs that can be used in migraine prophylaxis? (2)
1. Verapamil
2. Flunarizine
66
What is the serotonin antagonist that can be used in migraine prophylaxis?
Pizotifen
67
What are the 5 supplements/herbals that can be used in migraine prophylaxis?
1. Magnesium oxide*
2. Magnesium citrate*
3. Riboflavin*
4. Butterbur
5. Co-enzyme Q10
68
What is the target dose of magnesium oxide in migraine prophylaxis?
500mg po daily (elemental)
69
What is the target dose of magnesium citrate in migraine prophylaxis?
300 mg po daily
70
What is the target dose of riboflavin in migraine prophylaxis?
400mg po daily
71
What is the -gepant that can be used for migraine prophylaxis?
Atogepant
72
What are the 2 "others" that can be used for migraine prophylaxis?
1. Memantine (Alzheimer's drug)
2. Botox
