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Year 3 - Clinical (Winter) > 25 - Migraine/Headache > Flashcards

25 - Migraine/Headache Flashcards

1
Q

Pathophysiology of migraine

A
  • Complex phenomenon – vascular theory (vasodilation of cerebral vasculature = headache; vasoconstriction = aura) is no longer appropriate on its own
  • Is a neurological disorder
  • Cortical spreading depression phenomenon (CSD) thought to -> cause migraine aura, activate trigeminal nerve afferents, and disrupt blood-brain barrier permeability
  • Sensitization (peripheral and central) -> nerves become more responsive to stimuli
  • Know that activation of serotonin receptors is key for acute migraine tx, but we don’t really know why (many theories)
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2
Q

Migraine subtypes

A
  • Acute or “episodic” migraine w/ or w/o aura

- Chronic migraine w/ or w/o aura

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3
Q

Diagnostic criteria – acute migraine w/o aura **know this

A
  1. At least 5 attacks fulfilling criteria 2 through 4
  2. Headache attacks lasting 4 to 72 h (untreated or unsuccessfully treated)
  3. Headache has at least 2 of the following characteristics -> unilateral location, pulsating quality, moderate or severe pain intensity, aggravation by or causing avoidance of routine physical activity
  4. During headache at least 1 of the following -> N, V, or both; photophobia and phonophobia
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4
Q

Diagnostic criteria – acute migraine w/ aura **know this

A
  1. At least 2 attacks fulfilling criterion 2 and 3
  2. One or more of the following fully reversible aura sx:
    - Visual -> flickering lights, flashes, lines/shapes, spots
    - Sensory -> tingling and/or numbness of 1 limb, side of face and/or mouth/tongue
    - Speech and/or language -> aphasia/dysphasia, word-finding
    - Motor -> muscle weakness, loss of function
    - Brainstem -> dizziness, loss of balance
    - Retinal -> partial visual loss
  3. At least 2 of the following 4 characteristics:
    - At least 1 aura sx spreads gradually over 5 or more minute, and/or 2 or more sx occur in succession
    - Each individual aura sx lasts 5-60 mins
    - At least 1 aura sx is unilateral
    - Aura is accompanied, or followed w/in 60 mins, by headache
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5
Q

Diagnostic criteria – chronic migraine w/ or w/o aura **know this

A
  1. Headache (tension-type-like and/or migraine-like) on 15 or more days/month for > 3 months and fulfilling criteria 2 and 3
  2. Occurring in a pt who has had at least 5 attacks fulfilling criteria 2-4 for “acute migraine w/o aura” and/or criteria 2 and 3 for “acute migraine w/ aura”
  3. On 8 or more days/month for > 3 months, fulfilling any of the following:
    - Criteria 3 and 4 for “acute migraine w/o aura”
    - Criteria 2 and 3 for “acute migraine w/ aura”
    - Believed by the pt to be migraine at onset and relieved by a triptan or ergot derivative
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6
Q

Migraine phases

A
  • Phase 1 = prodrome
  • Phase 2 = aura
  • Phase 3 = early headache
  • Phase 4 = late headache
  • Phase 5 = postdrome
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7
Q

Premonitory sx (prodrome)

A
  • ~24-48 h before onset of headache
  • Neurologic sx (ex: allodynia, phonophobia, photophobia, hypersomnia, and difficulty concentrating)
  • Psychological (ex: anxiety, depression, euphoria, drowsiness, fatigue)
  • Autonomic (ex: polyuria, diarrhea, constipation)
  • Constitutional (ex: stiff neck, yawning, thirst, food cravings)
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8
Q

Describe phase 2 (aura)

A
  • Can precede and/or be present during headache
  • Lasts < 60 mins
  • Completely reversible
  • Mix of positive and negative focal neurological sx (not just visual and sensory):
    • Visual -> positive = flickering lights, spots, lines; negative = loss of vision
    • Sensory -> positive = pins and needles; negative = numbness
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9
Q

Characteristics of a typical migraine headache **know this

A
  • Unilateral (most often), but not always on the same side
  • Throbbing, pulsating
  • Attack progressively worsens over hours
  • Often N and V (vomiting less common)
  • Photophobia/ phonophobia (very common) -> often migraine sufferer will need to rest in dark, quiet room b/c of this
  • Osmophobia and cutaneous allodynia
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10
Q

Red flag migraine sx

A
  • Age of onset > 50 y/o
  • Severe and abrupt onset
  • Sx worsening over days/weeks
  • Neurologic signs -> stiff neck, focal signs, reduced consciousness, abnormal speech, cognitive impairment
  • Systemic signs -> fever, rash, N/V
  • New onset cancer, lyme disease, HIV
  • Triggered by cough, exertion, sexual activity
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11
Q

Migraine and stroke risk

A

**Take home message = women who have migraine w/o aura and no other risk factors for stroke may use a contraceptive pill w/ < 50 mcg estrogen; women who have migraine w/ aura should be encouraged to stop smoking, control their BP, and use an alternative method of contraception

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12
Q

Potential migraine triggers

A
  • Most common = emotional stress, hormones in women, not eating, weather, sleep disturbances
  • Moderately common = odours, neck pain, lights, alcohol, smoke, sleeping late, heat, food
  • Less common = exercise, sexual activity
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13
Q

Non-pharms for migraine

A
  • *Avoid triggers, hydration, maintain routine
  • Rest/sleep in dark, quiet room
  • Headache diary
  • Stress management
  • Cold/heat packs
  • Regular meals, caffeine balance
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14
Q

Pharmacotherapy options for migraine

A
  • Acute drug treatment (abortive medications, “relievers”) -> taken prn for headache sx
  • Preventative drug tx -> aim to decrease migraine frequency; taken on a regular basis
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15
Q

Goals of acute therapy

A
  • Relieve pain and associated sx of migraines
  • Functional headache-free state in 2 h w/ no recurrence in 24 h
  • Minimal or no adverse effects
  • Relieve migraine-related disability so that pt can return quickly to normal function
  • Avoid medication overuse headache and development of central sensitization (when abortive medications are less effective; can be prevented w/ early tx)
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16
Q

Benefit to treating the headache early

A
  • Early tx reduces overall burden of migraine (and reduces likelihood of central sensitization)
  • Challenges:
    • Some avoid medication unless headache is severe b/c of cost and SE
    • Some w/ frequent attacks limit acute medication for fear of overuse
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17
Q

Migraine – acute pharmacotherapy options

A
  • Triptans (5-HT receptor agonists) *migraine specific
  • Ergot derivatives (nonselective 5-HT agonist) *migraine specific
  • NSAIDs, acetaminophen
  • Domperidone, metoclopramide, prochlorperazine (anti-emetic)
  • *Best if taken early in attack (ie: at onset of head pain); taking at aura may be too soon
18
Q

Triptans for migraine (role, efficacy, MOA, CI)

A
  • Role -> moderate to severe migraine attacks (1st line)
  • Don’t seem as effective if taken during aura (take at pain onset)
  • All effective in reducing N/V, photo and phonophobia
  • 1/3 of px may not respond to triptan -> may benefit from switching to a different triptan (space 24 h)
  • MOA in migraine unclear (vasoconstrictor but also inhibits neurogenic inflammation peripherally and prevents central sensitization)
  • CI in px w/ CAD (despite evidence to suggest safe use)
  • Can use SC, ODT, or intranasal formulations if headache builds rapidly or is accompanied by early N/V; more expensive
  • All triptans require dose adjustment in liver dysfunction (some CI); some require dose adjustment in renal dysfunction
19
Q

Drug-drug interactions w/ triptans

A
  • Don’t take w/in 24 h of ergot alkaloid (additive vasoconstriction)
  • Avoid w/in 2 weeks of MAOIs
  • Caution w/ SSRI/SNRI (serotonin syndrome rare)
  • CYP3A4 inhibitors
  • Propranolol can increase serum concentrations of certain triptans (mostly rizatriptan, so reduce dose if needed)
20
Q

Triptans SE

A
  • Common = paresthesia’s, fatigue, dizziness, flushing, warm sensations, somnolence
  • “Triptan sensations” = mild and transient burning, tingling, tightness, pressure, pain in face/chest/neck/throat
  • Serious but rare = MI, coronary vasospasm w/ ischemia, serotonin syndrome
  • CI = cerebrovascular disease, IHD (angina, post-MI), uncontrolled HTN, PVD, hemiplegic or basilar migraine
21
Q

Ergots for migraine (role, MOA)

A
  • 1st line for severe/ultra-severe attacks
  • Non-selective 5-HT agonist
  • Also, alpha + beta-adrenergic agonist and dopamine D1 + D2 agonist (contributes to SE rather than migraine relief)
  • Brand name = migranal (dihydroergotamine)
    • Slower onset of action and less migraine recurrence than sumatriptan SC/IN
    • More N/V (pre-dose w/ antiemetic) but less chest pain than triptans
22
Q

Ergots SE

A
  • Common = N/V, abdominal pain, weakness, fatigue, muscle pain, diarrhea
  • Serious = severe peripheral ischemia (cold, numb, painful extremities), gangreneous extremities, MI, hepatic necrosis, bowel and brain ischemia
  • CI = cardiac/ cerebrovascular disease, uncontrolled HTN, pregnancy, hemiplegic or basilar migraine
  • Don’t use w/in 12 h of triptans
23
Q

Acetaminophen for migraine (role, efficacy)

A
  • Role -> acute migraine tx of mild to moderate severity; pt w/ CI or intolerance to NSAIDs
  • Best if taken early
  • May be less effective than NSAIDs, but superior to placebo
24
Q

NSAIDs for migraine (MOA, role, SE, caution)

A
  • Prevents inflammation in the trigeminovascular system via prostaglandin synthesis inhibition
  • Role -> acute migraine tx of mild to moderate severity
  • Can use alone or w/ metoclopramide 10 mg
  • SE = GI (dyspepsia, N/V, diarrhea), bleed, renal, rash
  • Avoid or caution in ulcer disease, gastritis/ esophagitis, renal disease, hypersensitivity
25
Q

Acute medications to avoid in migraine

A
  • Fiorinal -> contains butalbital (known for rebound headaches)
  • Opioids for migraine -> ideal limitation is maximum of 2 days/week; lack of evidence for superiority to NSAIDs/triptans
26
Q

What cause medication overuse headache? Which medications are low, moderate, and high risk?

A
  • Occurs from taking too much of an acute migraine reliever medication, for too long
  • Mechanisms unclear
  • Low risk (used 15 or days/month) = NSAIDs, acetaminophen, ASA
  • Moderate risk (used > 10 days/month) = triptans, ergotamine
  • High risk (used >5-10 days/month) = opioids (~8 days), ASA/ acetaminophen/ caffeine, use of > 1 acute med
27
Q

MOH signs and sx

A
  • AM sx -> often either present or develops upon waking; also, poor sleep quality
  • Poor acute tx response -> acute prn meds may only provide partial and/or temporary relief
  • Overuse of acute meds (>3 months)
  • 15 or more headache days per month (often daily) w/ pre-existing episodic migraine
  • Neck pain
  • Great variability in location, quality, and associated sx between px and within a pt; can change over time
28
Q

MOH management

A
  • Taper down/stop the offending drug
  • Watch for refractory rebound headache and withdrawal sx
  • Prophylactic tx may help reduce rebound and withdrawal sx
  • Renewed response to therapy usually occurs w/in 2 months of medication withdrawal (earliest 1-2 weeks)
29
Q

Acute migraine tx algorithm

A
  • Mild/moderate -> ASA, ibuprofen, naproxen, acetaminophen
    • Not responding -> triptans
  • Incomplete relief or frequent tx failure (tried at least 3 different triptans for 3 different attacks) -> triptan + NSAID
  • Not responding -> DHE + anti-nauseant
  • Not responding -> acetaminophen + codeine/tramadol (max 2 days/week)
  • If nausea, add either metoclopramide or domperidone
30
Q

Acute migraine tx in pregnancy (options and what to avoid)

A
  • Options -> non-pharms (especially in 1st trimester), acetaminophen, metoclopramide, sumatriptan (routine use not recommended)
  • Avoid -> ASA, NSAIDs, prochlorperazine, ergotamines
31
Q

Acute migraine tx in breastfeeding (options and what to avoid)

A
  • Options -> acetaminophen, NSAIDs (ibuprofen preferred), metoclopramide/ domperidone/ dimenhydrinate/ prochlorperazine, sumatriptan
  • Avoid -> ASA, codeine (especially if mother is UM), high-dose opioids
32
Q

When to consider prophylaxic tx for migraine

A
  • Frequent and/or long-lasting and/or severely debilitating migraines
  • Contraindication to acute therapies
  • Failure of acute therapy (either poor efficacy and/or intolerable SEs)
  • > 2 attacks per week (risk of MOH)
33
Q

Prophylactic tx for migraine

A
  • Probability of success w/ any one of the preventative drugs is 50-75% (success = 50% or greater reduction in h/a frequency)
  • Goals -> reduce attack frequency by at least 50% and reduce severity, reduce associated disability, prevent transition from acute to chronic migraine
  • May increase effectiveness/response of acute migraine tx
34
Q

Evidence-based medications for migraine prophylaxis

A
  • Beta blockers (metoprolol, propranolol, and timolol)
  • Antidepressants (amitriptyline and venlafaxine)
  • Anti-epileptics (valproate and topiramate)
  • Alternatives = CCBs (verapamil, flunarizine), ACEi/ARB (candesartan, lisinopril), butterbur
35
Q

Beta blockers for migraine (role, SE, CI)

A
  • Raises migraine threshold by modulating adrenergic system and 5-HT transmission in cortical pathways of brain
  • First line (especially in px < 60 y/o, HTN, or CVD)
  • Propranolol, metoprolol, and timolol have the most evidence
  • Beta blockers w/ intrinsic sympathomimetic activity (pindolol, acebutolol) may not be effective
  • SE = bradycardia, fatigue, hypotension, vivid dreams, depression
  • CI = asthma, heart block, uncompensated HF, peripheral vascular disease
36
Q

Antidepressants for migraine (role, SE, CI)

A
  • Consider in those w/ comorbidities (depression, insomnia, neuropathic pain, tension-type h/a)
  • TCAs -> amitriptyline = first line; conflicting evidence of other TCAs, but still used often in practice
    • Anticholinergic (avoid in BPH, glaucoma), sedation (dose HS), increased appetite, weight gain, orthostatic hypotension, cardiac toxicity (slower AV conduction)
    • CI = heart block, significant CVD, urinary retention, uncontrolled glaucoma, prostate disease, mania
  • SNRIs (venlafaxine) -> benefit if co-morbid anxiety/mood disorders
    • N/V, drowsiness, sexual dysfunction
    • Avoid in HTN, kidney failure
    • Monitor for serotonin syndrome especially if also on triptan
37
Q

Anticonvulsant drugs for migraine (role, which ones to use)

A
  • Role -> 2nd line for prophylaxis of severe migraine
    • Px w/ seizure disorder, anxiety, bipolar disorder
  • Valproic acid and topiramate have most evidence
    • Valproate = effective; CI in pregnancy
    • Topiramate = effective; titrate slowly from 15-25 mg daily up to 100-200 mg daily (b/c of rash?); category D in pregnancy
  • Gabapentin has moderate quality evidence for efficacy
    • Generally, well tolerated but somnolence is common
38
Q

Anticonvulsant drugs – safety

A
  • Valproic acid -> N/V, tremor, alopecia, weight gain, hepatotoxicity (rare)
    • Avoid in liver disease, bleeding disorders, pregnancy, obesity
  • Topiramate -> paresthesia, fatigue, anorexia, diarrhea, weight loss, memory impairment
    • Avoid in px w/ hx of kidney stones/failure, pregnancy, cognitive impairment, angle closure glaucoma
  • Gabapentin -> mild/transient somnolence, dizziness, tremor, ataxia
39
Q

Principles of prophylactic management of migraine

A
  • Start low and titrate slowly (to maximal dose, efficacy or to intolerable SE)
  • Trial drug for adequate period of time (delayed response) -> usually 2-3 months at target dose
  • Consider pt-specific characteristics in selection of prophylactic tx
  • Discuss expected benefits w/ px; make sure they are aware of what a tx success looks like
  • If tx failure, try drug from different therapeutic class
  • Lifestyle measures are a very important part of therapy
40
Q

Migraine prophylactic tx algorithm

A
  • 1st time prophylaxis -> propranolol, nadolol, metoprolol, amitriptyline, venlafaxine
  • Not responding -> try different class
  • Refractory -> specialist referral; combination beta blocker w/ topiramate or VPA or TCA; topiramate w/ TCA
41
Q

Pt specific factors when considering migraine prophylactic tx

A
  • High BMI -> topiramate
  • HTN -> beta blocker, candesartan, lisinopril
  • Mood/anxiety -> amitriptyline (nortriptyline), venlafaxine
  • Pregnant -> non-pharms, magnesium, propranolol/ metoprolol, amitriptyline (nortriptyline)
  • Lactation -> non-pharms, magnesium, propranolol/ nadolol/ metoprolol, amitriptyline (nortriptyline), valproate
42
Q

What are CGRP antagonists? Advantages, disadvantages, SE?

A
  • MAb for preventative tx of migraine
  • Target calcitonin gene-related peptide (CGRP) which is a vasodilatory neuropeptide w/ role in migraine
  • Don’t appear to have greater efficacy than other prophylactic tx
  • Advantages -> once monthly injection, well tolerated, specific targets (low risk of Dis)
  • Disadvantages -> no long-term safety data, increased stroke/MI risk?
  • Erenumab SE = constipation, Ab development, injection site reaction
  • Strongly consider for px w/ severe disability and lack of benefit from or unable to tolerate existing alternatives, difficulty adhering to daily medication regimens, polypharmacy
  • Caution in px who are concomitantly exposed to vasoconstrictive drugs or substances (CGRP blockade may be risky)

Year 3 - Clinical (Winter) (30 decks)

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