Migraines

Question 1

Migraines

Answer 1

primary headache disorder
recurring headaches (moderate to severe)
last 2-72 hours
sensitivity to normal sensory input
nausea/vomiting - general autonomic dysfunction

Question 2

Aura

Answer 2

visual disturbances (changes in cortical activity)
precede a migraine ~20% of time

Question 3

Cortical Spreading Depression

Answer 3

wave of neuronal depolarization leads to desensitization (refractory period)
cause of aura
blood flow increases and then decreases in correspondence with increase and decrease of neuronal activity

Question 4

familial hemiplegic migraine

Answer 4

autosomal dominant inheritance
weakness on half of body
genetic mutations:
- P/Q type Ca2+ channel
- Na+/K+ ATPase
- Na+ channel subunit
lower threshold for cortical spreading depression

Question 5

Trigeminal System

Answer 5

trigeminal nerve is the largest cranial nerve
opthalmic branch - eyes + top of head
maxillary branch - upper jaw
mandibular branch - lower jaw
senses pain and temperature in head
innervates dura mater
controls cerebral blood vessels

Question 6

Mechanism

Answer 6

pain is detected by opthalmic branch of trigeminal nerve - dura mater and blood vessels

Question 7

neurovascular disease

Answer 7

1. extra cerebral blood vessels dilate during migraine
2. cranial blood vessel stimulation leads to headache
3. vasoconstrictor drugs alleviate pain

Question 8

5-HT

Answer 8

release of serotonin - vasoconstriction
binds to 5-HT1b/d receptors on blood vessels
low levels between attacks - vasodilation leads to migraines
homeostasis - body releases 5-HT during migraine to decrease vasodilation

Question 9

CGRP

Answer 9

calcitonin gene-related peptide
in trigeminal peripheral afferents
released in response to pain = vasodilation
binds to receptors on smooth muscle

Question 10

treatment

Answer 10

prophylactic - taken daily to prevent attacks
abortive - taken once an attack occurs

Question 11

non pharmacological prophylactic

Answer 11

identify triggers - diet, sleep, exercise, caffeine

Question 12

pharmacological prophylactic

Answer 12

beta blockers (propanolol) decrease blood pressure
anticonvulsants (gabapentin) blocks pain transmission by binding to Ca2+ channel to decrease neuronal activity
antidepressants (amitriptyline) elevate serotonin levels - vasoconstriction

Question 13

non-specific analgesics

Answer 13

NSAIDs, acetaminophen, opioids
don’t work great (except for opioids)
risk of overdose, addiction - rebound headache

Question 14

caffeine

Answer 14

adenosine receptor antagonist (blood vessels) →vasoconstriction
increases absorption of analgesics

Question 15

Ergotamines

Answer 15

agonist for 5-HT1b/d receptors - inhibit neurogenic inflammation = vasoconstriction
less receptor selectivity = side effects
alpha 1 and 2 receptors - cardiovascular effects
oral administration - large first pass metabolism = low bioavailability

Question 16

Triptans

Answer 16

selective 5-HT1b/d agonist
vasoconstriction and inhibition of trigeminal nerve
avoids side effects
sumotriptan - orally = 14% bioavailability, subcutaneously = 96%
metabolized by MAO

Question 17

CGRP antagonists

Answer 17

small molecules block activation of CGRP receptor

Question 18

Olcegepant

Answer 18

poor bioavailability

Question 19

Telcagepant

Answer 19

increased liver enzymes

Question 20

Nurtek

Answer 20

effective + approved

Question 21

CGRP antibodies

Answer 21

larger molecules that bind to receptor
inhibit signalling = vasoconstriction