Migraine Therapy

Question 1

What is thought to be the cause of migraine with aura?

Answer 1

Cortical spreading depression

Question 2

What is thought to be the cause of migraine pain?

Answer 2

Activation of the trigeminovascular system

Question 3

What is the latest target in migraine drug development?

Answer 3

CGRP release from trigeminal ganglion neurons

Question 4

How can migraine pain be stopped?

Answer 4

Constricting blood vessels
Addressing seratonin levels
Targeting CGRP release

Question 5

What are 3 subtypes of serotonin receptors that are therapeutic targets for migraine?

Answer 5

5-HT1B (substantia nigra, globus pallidus, basal ganglia)
5-HT1Da,b (Brain, Sumatriptan is partially selective agonist here)
5-HT1F (cortex, hippocampus)

Question 6

Is prophylactic migraine therapy more effective in classic or common migraine?

Answer 6

Classic

Question 7

How do prophylactic migraine therapies work?

Answer 7

Elevate CSD threshold and suppress CSD

Question 8

What are the primary drugs used for migraine prophylaxis?

Answer 8

Beta-blockers (propranolol, timolol)

Anticonvulsants (valproate, topiramate)

Question 9

What are contraindications of beta blockers?

Answer 9

Asthma
Depression
Heart failure
Calcium channel blockers

Question 10

What is the mechanism of valproate in migraine therapy?

Answer 10

Increases GABA-mediated neurotransmission
> suppresses inflammation and nociceptive transmission
Modulates 5-HT > suppresses rostral brain stem modulator
CSD likely suppressed by reduced glutamaergic activity

Question 11

What is the mechanism of topiramate in migraine therapy?

Answer 11

Blocks sodium and calcium channels
Inhibits glutamate receptors
Enhances GABA activity
Inhibits activation of TNC

Question 12

How many migraine days per month are needed before using BoTox for chronic migraine?

Answer 12

15+

Question 13

What is the mechanism of onabotulinum toxin?

Answer 13

Cleaves snares in release of CGRP from peripheral trigeminal sensory nerve terminals which :

1. mitigates development of peripheral sensitization
2. central sensitization

Question 14

What drugs are good for treatment of acute migraine?

Answer 14

Mild to Moderate

• NSAIDs (naproxen), acetaminophen
• Caffeine
• Metoclopramide (anti-emetic, typically used as adjuvant)

Severe

• Ergots (ergotamine, dihydroergotamine)
• Triptans (sumatriptan)

Question 15

What is the mechanism of ergots (ergotamine, DHE)?

Answer 15

Cerebral vasoconstriction

Non-selective 5-HT agonist at trigeminal nerves

Question 16

How does DHE differ from ergotamine?

Answer 16

DHE has :
Fewer adverse effects
Weaker vasoconstriction
Parenteral administration (and nasal) for faster results

Question 17

What drug interactions are there with ergots?

Answer 17

Triptans
Beta blockers
Nicotine

Question 18

What is the mechanism of triptans (sumatriptan)?

Answer 18

Selective agonists at 5-HT1 receptors

Question 19

What drugs should be avoided with triptans in order to reduce likelihood of catecholamine crisis?

Answer 19

MAOIs

Question 20

Sumatriptan is a derivative of what?

Answer 20

Serotonin

Question 21

Are ergots or triptans more effective later in the course of a migraine?

Answer 21

Triptans