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PHAR255 > Migraines & Headache > Flashcards

Migraines & Headache Flashcards

1
Q

Describe a simplified pathophysiology of migraines.

A
  1. some people have sensitized neurons (unclear)
  2. a migraine trigger comes along
  3. brain releases potent vasodilators (CGRP, NO) and inflammation reactions
  4. vasodilation=big pain; inflammation begets more inflammation
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2
Q

What is the MOA of triptans?

A

selective serotonin agonists = vasoconstrictors

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3
Q

What is the MOA of NSAIDs?

A

anti-inflammation

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4
Q

What is the MOA of anti-CGRP drugs?

A

prevent/reduce vasodilation

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5
Q

What is critical with migraine treatment in regards to the timing of treatment?

A

early treatment=nip it in the bud=better efficacy
-hitting inflammation early is critical

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6
Q

What is migraine aura?

A

early warning sign of migraine

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7
Q

What percentage of people with migraines experience aura?

A

30%

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8
Q

What are the symptoms of aura?

A

visual aura (90% of symptoms)
-lightning bolts, blind spots, flickering bright lines
sensory disturbances
-tingling, numbness, pins and needles
speech disturbances
-difficulty word-finding

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9
Q

What are some migraine triggers?

A

stress
meal skipping
foods
alcohol
caffeine withdrawal
dehydration
menstruation
lights/sunlight
erratic sleep/shift work
perfume/odour
obesity
change in barometric pressure

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10
Q

What is the mnemonic used to help in the diagnosis of a migraine?

A

POUND
-pulsatile
-one day duration(4-72h if untreated or poor treatment)
-unilateral headache
-nausea or vomiting
-disabling intensity
each one is worth 1 point

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11
Q

What is the likelihood of migraine based on points derived from the POUND mnemonic?

A

4-5 pts = 92%
3 pts = 64%
0-2 pts = 17%

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12
Q

Describe a simplified treatment approach to acute migraine.

A
  1. NSAID
    -cheap
    -response in 4-5/10 patients
  2. triptan
    -bit of a boost compared to NSAIDs
    -can start here
    -response in 5-6/10 patients
  3. NSAID + triptan
    -combining is better than one alone
    -response in 6-7/10 patients
  4. subcutaneous sumatriptan
    -can start here if really bad migraines
    -response in 8/10 patients
  5. refractory patients
    -manage agent failure
    -try alt combinations (acet, NSAIDs, triptans, metoclopramide, caffeine)
    -start migraine prophylaxis
    -possibly try DHE nasal spray
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13
Q

What is “response” defined as for acute migraines?

A

pain relief at 2 hours
-placebo response is 2-3/10 patients

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14
Q

Which agent has the fastest onset for acute migraine?

A

subcutaneous sumatriptan

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15
Q

Which drugs should be avoided in acute migraine?

A

opioids and barbiturates
-risk of MOH, AE, and overdose
-not doing anything for inflammation
-2x as likely to cause MOH

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16
Q

Which agent can be added anywhere along the treatment approach to acute migraine to improve efficacy and decrease nausea?

A

metoclopramide
-anti emetic by speeding up GIT motility
-faster absorption of other drugs

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17
Q

What is the DHE nasal spray?

A

dihydro ergotamine
-hits 5HT receptors but dirtier (more AE)
-almost never used

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18
Q

How can we manage NSAID failure for acute migraine?

A

ensure NSAID is taken at earliest onset of migraine pain and on an empty stomach (food delays onset)
try a faster-acting NSAID formulation (10-20 min faster than regular tabs)
-naproxen sodium, ibuprofen liquid gels, diclofenac potassium

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19
Q

Differentiate naproxen sodium and naproxen base.

A

naproxen sodium is 20-30min faster than naproxen base
-sodium of choice for migraine

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20
Q

What are the benefits of migraine prophylaxis?

A

decrease intensity of migraines and less migraines
decreasing intensity helps boost efficacy of other drugs

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21
Q

How can we manage triptan failure for acute migraine?

A

ensure triptan is taken at earliest onset of migraine pain
switch to a different triptan
-try for at least 3 different migraines (not a class response)
add acetaminophen, NSAID, or metoclopramide
ensure adequate absorption
-switch to injectable or nasal spray if vomiting dose
fast-acting triptan often preferred but if tolerability concerns then try slow-onset triptan

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22
Q

What are the slow-onset triptans?

A

naratriptan
frovatriptan

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23
Q

What are the fast-acting triptans?

A

eletriptan
almotriptan
rizatriptan
sumatriptan
zolmitriptan

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24
Q

Why should Tylenol #3 be avoided for migraines in almost every patient?

A

opioids have double the risk of MOH
caffeine dose is subtherapeutic
-~100mg needed for migraine efficacy, T3 has 15mg
acetaminophen dose is often subtherapeutic
-1000mg has best evidence, would need T3 x 3
codeine metabolism is unpredictable

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25
Q

What are the side effects and contraindications of triptans?

A

triptans are potent vasoconstrictors
-chest discomfort/tightness, palpitations, dizziness, flushing
-CI in CV disease (uncontrolled HTN, previous stroke/MI, etc)
-CI within 24h of ergots due to coronary vasospasm; do not combine triptans
triptans are potent 5HT agonists
-nausea
-CI with MAOI (serotonin syndrome) and caution with other serotonergic drugs (increase monitoring)

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26
Q

What are some considerations when deciding which triptan is best for your patient?

A

fastest relief: 10-15min with SC or nasal
best efficacy at 2hr: SC suma
-lowest efficacy at 2hr: nara or frova
best tolerability: slow onset or nara or frova decreases AE or nausea
best if long-lasting attacks: nara or frova
best for privacy: ODT (no H20)
lower cost: almo po
useful if vomiting: SC or nasal or add antiemetic

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27
Q

True or false: all triptans have similar safety in hepatic and renal disease

A

false

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28
Q

Which triptan has the highest efficacy?

A

SC sumatriptan
-works in up to 80% of patients
-useful if vomiting/severe nausea with oral agents
-guarantee absorption

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29
Q

What are some tips and tricks for acute migraines?

A

try a triptan for at least 3 migraines before giving up and try at least 3 triptans before giving up on the class
acetaminophen alone or in combo can be helpful
-overall less powerful than NSAIDs
N/V is common with migraines
-ODT, antiemetic, intranasal, injectable = all useful

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30
Q

True or false: ODT triptans are faster than regular tabs

A

false
they are not buccal, absorbed in the intestine
useful if water causes nausea

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31
Q

What is the max days per month of acute meds to help avoid MOH?

A

opioids: 9 days
triptans: 9 days
NSAIDs or acet: 14 days
multiple classes: 9 days

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32
Q

What is menstrual migraine?

A

for some, migraines increase during menstruation

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33
Q

What are the options for pre-treatment of menstrual migraine?

A

start ~2 days before treatment
-naproxen 500mg BID x ~6 days
-frovatriptan 2.5mg BID x ~6 days
-naratriptan 1mg BID x ~6 days
-estradiol gel 1.5mg daily x 7 days
option for prevention with continuous CHC
-but CHC + migraine with aura = CI

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34
Q

What are the available anti-CGRP drugs?

A

ubrogepant
-treatment dose: 50-100mg stat
rimegepant and zavegepant (USA)
atogepant approved for prevention
-10-60mg daily

35
Q

What are the adverse effects of the anti-CGRP drugs?

A

nausea
somnolence

36
Q

What are the benefits of the anti-CGRP drugs?

A

not CI in CV disease
very low risk of MOH

37
Q

What is a con of the anti-CGRP drugs?

A

not as effective for acute migraine
-although not compared head to head

38
Q

Who should consider utilizing migraine prophylaxis?

A

patient preference
-patient prefers prophylaxis for any reason
frequent attacks
-e.g. > 6 headache days/month
severely disabling attacks
-especially if > 3/month
difficult-to-treat attacks
-acute tx doesnt work well, is CI, or causes problems

39
Q

Describe the steps in setting up an adequate trial for migraine prophylaxis.

A
  1. initiate a headache diary
  2. start a migraine prevention drug at a low dose
  3. increase dose gradually q1-2wks guided by target dose range, patient response and tolerability
  4. remain at that dose for ~8-12wks to assess effectiveness and tolerability
  5. assess and decide whether to continue, increase the dose, or taper/dc
40
Q

Which agents have the best efficacy data for migraine prophylaxis?

A

amitriptyline 50-75mg/d hs
propranolol 80-160mg/d
metoprolol 100-200mg/d
topiramate 100mg/d

41
Q

Which agents for migraine prophylaxis have the fewest adverse effects?

A

candesartan 16mg/d
magnesium 500-600mg/d
riboflavin 400mg/d

42
Q

Which agent might be tried for migraine prophylaxis if the patient wants to pursue smoking cessation?

A

nortriptyline

43
Q

Which agent might be tried for migraine prophylaxis if the patient experiences insomnia?

A

amitriptyline

44
Q

Which agent might be tried for migraine prophylaxis if the patient has hypertension?

A

beta-blocker
candesartan
lisinopril
verapamil

45
Q

Which agent might be tried for migraine prophylaxis if the patient has chronic pain?

A

amitriptyline
venlafaxine
duloxetine
topiramate
possibly gabapentin

46
Q

Which agent might be tried for migraine prophylaxis if the patient has depression or anxiety?

A

venlafaxine
duloxetine
amitriptyline

47
Q

What are some tips and tricks for migraine prophylaxis?

A

set realistic expectations
-decrease in migraine days/month by >50%; less severe headaches
use a headache diary
-watch for triggers & track medication effectiveness + tolerability
be patient: allow time to stabilize on an effective dose
-effectiveness increases with time
-tolerability improves with time
help manage side effects

48
Q

What are the next steps if a trial of migraine prophylaxis fails?

A

consider:
-another drug class
-combo therapy
-a CGRP antagonist if failure with 2 or more agents

49
Q

How long should we treat at target dose before deciding if prophylaxis is helping?

A

8-12 weeks

50
Q

Which beta-blockers are used for migraine prophylaxis and what are their target doses?

A

propranolol: 40-80mg BID, 80-160mg LA
metoprolol: 50-100mg BID, 100-200mg SR
timolol: 10-15mg BID

51
Q

Which TCAs are used for migraine prophylaxis and what are their target doses?

A

amitriptyline: 50-75mg hs
nortriptyline: 50-75mg hs

52
Q

Which anticonvulsants are used for migraine prophylaxis and what are their target doses?

A

topiramate: 50mg BID
divalproex: 500-750mg BID cc

53
Q

What is a caution with anticonvulsants as migraine prophylaxis?

A

caution with women of child-bearing age

54
Q

Which ACEI and ARBs are used for migraine prophylaxis and what are their target doses?

A

candesartan: 16mg daily
lisinopril: 20mg daily

55
Q

Which SNRIs are used for migraine prophylaxis and what are their target doses?

A

venlafaxine 150mg daily
duloxetine: 60mg daily

56
Q

What is the target dose of pizotifen for migraine prophylaxis?

A

1.5mg hs

57
Q

What is the MOA of pizotifen?

A

serotonin antagonist

58
Q

What is an adverse effect of pizotifen?

A

very sedating

59
Q

Which CCBs are used for migraine prophylaxis and what are their target doses?

A

flunarazine: 10mg hs
verapamil: 240mg daily with food

60
Q

Which herbals are used for migraine prophylaxis and what are their target doses?

A

magnesium oxide: 500mg elemental daily
magnesium citrate: 300mg BID
riboflavin: 400mg daily

61
Q

What is an adverse effect of high dose riboflavin?

A

neon-yellow urine

62
Q

What are the anti-CGRPs used for migraine prophylaxis?

A

fremanezumab: 225mg SC q4wk or 675mg SC q12wk
eptinezumab
erenumab
galcanezumab
atogepant
rimegepant

63
Q

What are some “other” drugs used for migraine prophylaxis?

A

memantine: 10mg hs
Botox: maybe if > 15 migraine days/month

64
Q

What is a critical drug interaction of propranolol with respect to migraines?

A

slows metabolism of rizatriptan and thus levels increase 70%

65
Q

How can we manage the propranolol-rizatriptan drug interaction?

A

use 5mg rizatriptan tabs instead of 10mg
change triptans
change beta-blockers

66
Q

What is the MOA of the CGRP MABs?

A

MAB targeting calcitonin gene-related peptide

67
Q

What is the response rate of the CGRP MABs?

A

40% of patients

68
Q

Which CGRP MAB is covered by Sask and NIHB?

A

fremanezumab
-failed two po prophylactic agents

69
Q

How frequently is fremenazeumab dosed?

A

can be given q3mo but prefer monthly (better Css)

70
Q

What are the adverse effects of CGRP MABs?

A

injection site rxn
hypertension

71
Q

What are the red flags of acute headache?

A

emergency (call for ambulance)
-worst HA
-impaired speech, strength, sensation, consciousness
-neck stiffness or fever
-thunderclap HA
-head trauma
-eye symptoms
urgent (send for referral)
-first ever headache
-headache with exercise or sex
-new headache if age >50 yrs
-HIV, cancer, lyme dx, pregnancy
-papilledema
-older adult with cognitive changes

72
Q

What are the different types of headaches?

A

migraine
tension type
cluster

73
Q

Describe migraines based on the following:
-duration
-location
-pain description
-symptoms
-acute tx
-prophylaxis

A

duration: 4-72h
location: typically unilateral (but 40% bilateral)
pain: pulsating, mod-severe
sx: N/V, photophobia, phonophobia, aura (5-60min), triggers
acute tx: NSAIDs, acet, triptan, anti-emetic, DHE
prophylaxis: BB, TCA, topiramate, candesartan, herbs, anti-CGRP, venlafaxine

74
Q

Describe tension type headache based on the following:
-duration
-location
-pain description
-symptoms
-acute tx
-prophylaxis

A

duration: 30min-7d
location: typically bilateral
pain: photo or phonophobia, NO N/V, not usually triggered by routine activity
acute tx: NSAIDs, acet
prophylaxis: TCA

75
Q

Differentiate frequent and infrequent TTH.

A

infrequent: < 1 day/month average
frequent: 1-14 days/month average

76
Q

Describe cluster headache based on the following:
-duration
-location
-pain description
-symptoms
-acute tx
-prophylaxis

A

duration: 15min-3h (untreated)
location: unilateral, orbital, supraorbital, temporal, combo
pain: stabbing, nonpulsating, severe to excruciating
sx: clusters qod up to 8 HA/d, ipsilateral, nasal, eye, sweating, restlessness
acute tx: SC sumatriptan
prophylaxis: verapamil (240-960mg/d)

77
Q

Differentiate episodic and chronic cluster headache.

A

episodic: 2 cluster periods lasting 7-365d, remissions of >1 month
chronic: episodes recur for >1 year without remission or with remission lasting < 1 month

78
Q

What is MOH?

A

chronic HA caused by the overuse of acute HA medication that often provides inadequate pain relief
- > 15 HA days/month
-common to wake up with a daily HA

79
Q

What causes MOH?

A

> 9 days/month of triptans or opioids
14 days/month of NSAIDs or acet
9 days/month of combo

80
Q

How can we break the cycle of MOH?

A

recognize MOH
stop the overused med
create a prevention and treatment plan to avoid relapse

81
Q

How is MOH treated?

A

stopping the overused medication
stop or taper the overused med while starting a prophylactic med
start prophylactic med only

82
Q

What is considered resolution of MOH?

A

return to episodic headaches ( < 15 days/month)
-allow 3 months to establish new baseline

83
Q

What are some tips and tricks for treating MOH?

A

educate all patients on risk of MOH
prophylactic meds may become more effective once the overused med is stopped
headache diaries
non-drug approaches

84
Q

What are the withdrawal symptoms of MOH?

A

HA will increase in pain and frequency before they improve
anxiety, NV, sleep issues
generally last 2-10 days but can be up to 2-4wks
meaningful improvement in HA frequency usually 4-8wks

PHAR255 (24 decks)

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