Migraine

Question 1

what is the leading cause of disability worldwide in those under 50?

Answer 1

migraine

Question 2

what is a migraine?

Answer 2

primary headache disorder characterized by recurring moderate to severe, pulsating headaches that can last from 2-72 hours

Question 3

t/f: migraines can cause a sensitivity to light, sound, and head movements

Answer 3

true, any normal sensory input

Question 4

t/f: migraines won’t cause nausea or vomiting

Answer 4

false

Question 5

what is migraine aura?

Answer 5

visual disturbances such as flashing lights or zigzag lines that precede a migraine (~20%)

Question 6

what is thought to drive migraine aura?

Answer 6

cortical spreading depression

Question 7

what is cortical spreading depression?

Answer 7

wave of neuronal depolarization followed by period of desensitization/depression (ref. period) that propagates across cortex

Question 8

what are 2 factors that can incr migraine risk?

Answer 8

genetic and enviro

Question 9

do migraines affect women or men more?

Answer 9

women

Question 10

in women, when does migraine incidence incr?

Answer 10

after puberty (hormones?)

Question 11

what type of migraine has genetic contribution?

Answer 11

familial hemiplegic migraines (FHM)

Question 12

what are FHMs?

Answer 12

migraines that include weakness in half the body

Question 13

what kind of inheritance does FHM exhibit?

Answer 13

autosomal dominance (haplosufficient)

Question 14

what are 3 known genetic mutations associated w/ FHM?

Answer 14

P/Q-type Ca channels, Na/K ATPases, Na channel subunit

Question 15

how do mutations affect the threshold for cortical spreading depression?

Answer 15

decr threshold (incr risk)

Question 16

what is the trigeminal system?

Answer 16

sensory/motor innervation of the face and skull

Question 17

what is the largest cranial nerve?

Answer 17

trigeminal nerve

Question 18

what are the 3 branches of peripheral trigeminal processes?

Answer 18

ophthalmic (top), maxillary (middle), mandibular (bottom)

Question 19

what are 3 purposes of the trigeminal system?

Answer 19

sense pain/temp in head region, innervate dura mater, control cerebral blood vessels

Question 20

what is the dura mater?

Answer 20

membrane that surrounds the brain

Question 21

what is the system that controls cerebral blood vessels?

Answer 21

trigeminovascular system

Question 22

what branch of the trigeminal nerve detects pain in the head?

Answer 22

ophthalmic (top 1/3) innervating dura mater and blood vessels

Question 23

what kind of disease are migraines thought to be?

Answer 23

neurovascular

Question 24

what are 3 observations of migraines?

Answer 24

1. extracerebral vessels dilate during migraine
2. cranial blood vessel stimulation provokes headache
3. vasoconstrictor drugs alleviate pain

Question 25

release of what NT leads to vasoconstriction?

Answer 25

5-HT

Question 26

when are 5-HT levels low vs high in migraineurs?

Answer 26

low: btwn migraines high: during migraine

Question 27

what 5-HT receptor in particular is associated w/ vasoconstriction for migraines?

Answer 27

5-HT 1D

Question 28

incr of what molecule is associated w/ migraines?

Answer 28

calcitonin gene-related peptide (CGRP)

Question 29

where is CGRP located?

Answer 29

in trigeminal peripheral afferents (on nociceptors)

Question 30

what is CGRP released in response to?

Answer 30

pain (from afferents)

Question 31

what do high levels of CGRP cause? (2)

Answer 31

vasodilation and migraine

Question 32

what are the 2 treatment strategies for migraines?

Answer 32

prophylactic and abortive

Question 33

whats the difference btwn prophylactic vs abortive migraine strategies?

Answer 33

prophylactic: taken daily to prevent migraines abortive: taken when an attack occurs

Question 34

what are non-pharmacological prophylactic migraine interventions?

Answer 34

identify and reduce triggers (diet, exercise, sleep, caffeine, alcohol, stress)

Question 35

what are 3 pharmacological prophylactic migraine interventions?

Answer 35

beta-blockers (propranolol-decr BP), anticonvulsants (gabapentin-decr pain transmission), antidepressants (amitriptyline-SSRI)

Question 36

what are 4 examples of abortive migraine drugs?

Answer 36

aspirin, acetaminophen, NSAIDs, opioids (non-specific analgesics)

Question 37

what is the risk of taking non-specific analgesics for chronic migraines?

Answer 37

medication overuse headache (make headache worse)

Question 38

what is caffeine?

Answer 38

adenosine receptor antagonist

Question 39

what does caffeine binding to adenosine receptors cause?

Answer 39

vasoconstriction (antagonism)

Question 40

what is an additional benefit of caffeine for migraines?

Answer 40

incr absorption of some analgesics (acetaminophen, ergotamines) which improves migraine treatment during attack (improve rate/extent of absorption)

Question 41

what is an adverse effect of using caffeine for migraines?

Answer 41

can trigger headaches or rebound headaches/withdrawal

Question 42

what were the 1st specific anti-migraine agents (1926) but aren't 1st line therapy anymore?

Answer 42

ergotamines (ergot alkaloid - like LSD)

Question 43

what are ergotamines/ergot alkaloids?

Answer 43

5HT-1b/d agonists

Question 44

what does ergotamines/ergot alkaloids binding to 5HT-1b/d Rs cause?

Answer 44

vasoconstriction that inhibits neurogenic inflammation (blocks migraine)

Question 45

what is the issue with ergotamines/ergot alkaloids for migraines?

Answer 45

low receptor selectivity which incr risk of side effects (like LSD)

Question 46

ergotamines/ergot alkaloids having low receptor selectivity can cause what?

Answer 46

can bind to a-adrenergic Rs and produce coronary vasoconstriction (ischemic changes/anginal pain in coronary artery diseased ppl)

Question 47

what are 4 contraindications of using ergotamines/ergot alkaloids for migraines?

Answer 47

peripheral vascular disease, coronary heart disease, uncontrolled hypertension, stroke

Question 48

what is the absorption/distribution of ergotamines? (2)

Answer 48

large first-pass metabolism (oral), low bioavailability (<1%)

Question 49

what is the metabolism and half-life of ergotamines?

Answer 49

metabolized by poorly-defined liver enzymes, half-life is 2hrs

Question 50

where are ergotamines excreted?

Answer 50

bile

Question 51

what is the first-line migraine therapy? ex?

Answer 51

triptans, sumatriptan

Question 52

what are triptans?

Answer 52

selective 5HT-1b/d agonists (~ergotamines)

Question 53

what are 2 effects/mechanisms of triptans?

Answer 53

vasoconstriction and inhibition of trigeminal nerve (5HT-1b/d Rs on blood vessels and peripheral pain neurons)

Question 54

do triptans have similar side effects to ergotamines? why?

Answer 54

no, avoid ergotamine side effects bcse are more selective (decr a-adrenergic binding)

Question 55

what is the bioavailability (absorption/distribution) of sumatriptan when taken orally vs subcutaneously?

Answer 55

14% when oral, 96% subcutaneously

Question 56

what metabolizes sumatriptan and its half-life?

Answer 56

monoamine oxidase (also 5-HT), half-life is 2hrs

Question 57

where is sumatriptan excreted?

Answer 57

urine

Question 58

what do CGRP antagonists do?

Answer 58

prevents CGRP binding during a migraine causing vasodilation (CGRP released from trigeminal pain afferents)

Question 59

what are 2 forms of CGRP antagonists?

Answer 59

small-molecule CGRP antagonists or monoclonal antibodies for CGRP/CGRP receptors

Question 60

what are the 6 stages of clinical drug trials?

Answer 60

preclinical (research), phase 1 (safety), phase 2 (efficacy), phase 3 (detect side effects), FDA review, phase 4

Question 61

why is 5-HT low btwn migraines and high during migraines if it leads to vasoconstriction?

Answer 61

btwn: low levels account for susceptibility to migraine (decr vasoconstrictors) during: released as a rxn to vasodilation