Lecture 9: Anti-migraine drugs

Question 1

Debilitating headache disorder

Answer 1

recurring
affects only one head unilateral
pulsating

Question 2

symptoms of prodrome

Answer 2

feelings of elation and intense energy
feelings of depression
craving for sweets
thirst
irritability drowsiness

Question 3

Aura: stage 1

Answer 3

vasoconstriction of arteries (ischemia)
not enough blood flow to brain

cortical spreading depression (CSD)

Question 4

Aura: stage 2

Answer 4

aura disappears
vasoconstriction becomes vasodilation
concomitant stimulation of trigeminal nerve (TGN) endings release neuropeptides
produce swelling and send pain signals

Question 5

Inflammation muscle contraction: stage 3

Answer 5

pain becomes more diffuse
release of inflammatory chemicals in the brain
photophobia
pain continues

Question 6

Post-headache: stage 4

Answer 6

relief
fatigue

Question 7

Familial Hemiplegic Migraine (FMH)

Answer 7

autosomal dominant subtype of migraine with aura
point mutations
increase synaptic glutamate

Question 8

3 steps in the cause of migraine in the brain

Answer 8

1) excited brain cells activate perivascular sensory trigeminal nerves to release vasoactive neurogenic peptides
1. substance P
2. calcitonin gene-related peptide (CGRP)
3. neurokinin A
2) produce inflammation and swelling of blood vessels
3) swollen blood vessels send pain signals to brainstem pain centres

Question 9

Serotonin role in migraine

Answer 9

serotonin receptors can reduce release of CGRP and substance P
induce vasoconstriction

Question 10

Metoclopramide

Answer 10

dopamine D2R antagonist
relief nausea and vomiting
does not relief migraine pain

Question 11

NSAIDs and antihistamine

Answer 11

ibuprofen or aspirin
most effective when taken onset of migraine

Question 12

Opiates and lidocaine

Answer 12

pain killer
no effect on mechanisms of migraine

lidocaine - local anesthetic
nasal drop

Question 13

Triptans (Sumatriptan)

Answer 13

agonist that bind to 5-HT receptors (serotonin receptors)
produce vasoconstriction and inhibit release of neurogenic peptide (substance P, CGRP, neurokinin A) from trigeminal nerves
side effect: nausea, dizziness, fatigue and VASOCONSTRICTION

Question 14

Gepants (Ubrogepant)

Answer 14

CGRP receptor antagonist
side effect: nausea, somnolence, dry mouth, dizziness
WILL NOT TRIGGER VASOCONSTRICTION, so no cardiovascular effect

Question 15

Antihypertensive to treat migraine

Answer 15

Prevent vasoconstriction at stage 1 aura

Question 16

Anti-seizure medication to treat migraine

Answer 16

Topiramate: GABAa agonist (first-line)
Valproate: Sodium channel blocker
prevent excitation of neurons