Migraine Flashcards
what is the leading cause of disability worldwide in those under 50?
migraine
what is a migraine?
primary headache disorder characterized by recurring moderate to severe, pulsating headaches that can last from 2-72 hours
t/f: migraines can cause a sensitivity to light, sound, and head movements
true, any normal sensory input
t/f: migraines won’t cause nausea or vomiting
false
what is migraine aura?
visual disturbances such as flashing lights or zigzag lines that precede a migraine (~20%)
what is thought to drive migraine aura?
cortical spreading depression
what is cortical spreading depression?
wave of neuronal depolarization followed by period of desensitization/depression (ref. period) that propagates across cortex
what are 2 factors that can incr migraine risk?
genetic and enviro
do migraines affect women or men more?
women
in women, when does migraine incidence incr?
after puberty (hormones?)
what type of migraine has genetic contribution?
familial hemiplegic migraines (FHM)
what are FHMs?
migraines that include weakness in half the body
what kind of inheritance does FHM exhibit?
autosomal dominance (haplosufficient)
what are 3 known genetic mutations associated w/ FHM?
P/Q-type Ca channels, Na/K ATPases, Na channel subunit
how do mutations affect the threshold for cortical spreading depression?
decr threshold (incr risk)
what is the trigeminal system?
sensory/motor innervation of the face and skull
what is the largest cranial nerve?
trigeminal nerve
what are the 3 branches of peripheral trigeminal processes?
ophthalmic (top), maxillary (middle), mandibular (bottom)
what are 3 purposes of the trigeminal system?
sense pain/temp in head region, innervate dura mater, control cerebral blood vessels
what is the dura mater?
membrane that surrounds the brain
what is the system that controls cerebral blood vessels?
trigeminovascular system
what branch of the trigeminal nerve detects pain in the head?
ophthalmic (top 1/3) innervating dura mater and blood vessels
what kind of disease are migraines thought to be?
neurovascular
what are 3 observations of migraines?
- extracerebral vessels dilate during migraine
- cranial blood vessel stimulation provokes headache
- vasoconstrictor drugs alleviate pain
release of what NT leads to vasoconstriction?
5-HT
when are 5-HT levels low vs high in migraineurs?
low: btwn migraines
high: during migraine
what 5-HT receptor in particular is associated w/ vasoconstriction for migraines?
5-HT 1D
incr of what molecule is associated w/ migraines?
calcitonin gene-related peptide (CGRP)
where is CGRP located?
in trigeminal peripheral afferents (on nociceptors)
what is CGRP released in response to?
pain (from afferents)
what do high levels of CGRP cause? (2)
vasodilation and migraine
what are the 2 treatment strategies for migraines?
prophylactic and abortive
whats the difference btwn prophylactic vs abortive migraine strategies?
prophylactic: taken daily to prevent migraines
abortive: taken when an attack occurs
what are non-pharmacological prophylactic migraine interventions?
identify and reduce triggers (diet, exercise, sleep, caffeine, alcohol, stress)
what are 3 pharmacological prophylactic migraine interventions?
beta-blockers (propranolol-decr BP), anticonvulsants (gabapentin-decr pain transmission), antidepressants (amitriptyline-SSRI)
what are 4 examples of abortive migraine drugs?
aspirin, acetaminophen, NSAIDs, opioids (non-specific analgesics)
what is the risk of taking non-specific analgesics for chronic migraines?
medication overuse headache (make headache worse)
what is caffeine?
adenosine receptor antagonist
what does caffeine binding to adenosine receptors cause?
vasoconstriction (antagonism)
what is an additional benefit of caffeine for migraines?
incr absorption of some analgesics (acetaminophen, ergotamines) which improves migraine treatment during attack (improve rate/extent of absorption)
what is an adverse effect of using caffeine for migraines?
can trigger headaches or rebound headaches/withdrawal
what were the 1st specific anti-migraine agents (1926) but aren’t 1st line therapy anymore?
ergotamines (ergot alkaloid - like LSD)
what are ergotamines/ergot alkaloids?
5HT-1b/d agonists
what does ergotamines/ergot alkaloids binding to 5HT-1b/d Rs cause?
vasoconstriction that inhibits neurogenic inflammation (blocks migraine)
what is the issue with ergotamines/ergot alkaloids for migraines?
low receptor selectivity which incr risk of side effects (like LSD)
ergotamines/ergot alkaloids having low receptor selectivity can cause what?
can bind to a-adrenergic Rs and produce coronary vasoconstriction (ischemic changes/anginal pain in coronary artery diseased ppl)
what are 4 contraindications of using ergotamines/ergot alkaloids for migraines?
peripheral vascular disease, coronary heart disease, uncontrolled hypertension, stroke
what is the absorption/distribution of ergotamines? (2)
large first-pass metabolism (oral), low bioavailability (<1%)
what is the metabolism and half-life of ergotamines?
metabolized by poorly-defined liver enzymes, half-life is 2hrs
where are ergotamines excreted?
bile
what is the first-line migraine therapy? ex?
triptans, sumatriptan
what are triptans?
selective 5HT-1b/d agonists (~ergotamines)
what are 2 effects/mechanisms of triptans?
vasoconstriction and inhibition of trigeminal nerve (5HT-1b/d Rs on blood vessels and peripheral pain neurons)
do triptans have similar side effects to ergotamines? why?
no, avoid ergotamine side effects bcse are more selective (decr a-adrenergic binding)
what is the bioavailability (absorption/distribution) of sumatriptan when taken orally vs subcutaneously?
14% when oral, 96% subcutaneously
what metabolizes sumatriptan and its half-life?
monoamine oxidase (also 5-HT), half-life is 2hrs
where is sumatriptan excreted?
urine
what do CGRP antagonists do?
prevents CGRP binding during a migraine causing vasodilation (CGRP released from trigeminal pain afferents)
what are 2 forms of CGRP antagonists?
small-molecule CGRP antagonists or monoclonal antibodies for CGRP/CGRP receptors
what are the 6 stages of clinical drug trials?
preclinical (research), phase 1 (safety), phase 2 (efficacy), phase 3 (detect side effects), FDA review, phase 4
why is 5-HT low btwn migraines and high during migraines if it leads to vasoconstriction?
btwn: low levels account for susceptibility to migraine (decr vasoconstrictors)
during: released as a rxn to vasodilation
