Flashcards in Migraine Therapy Deck (21)
What is thought to be the cause of migraine with aura?
Cortical spreading depression
What is thought to be the cause of migraine pain?
Activation of the trigeminovascular system
What is the latest target in migraine drug development?
CGRP release from trigeminal ganglion neurons
How can migraine pain be stopped?
Constricting blood vessels
Addressing seratonin levels
Targeting CGRP release
What are 3 subtypes of serotonin receptors that are therapeutic targets for migraine?
5-HT1B (substantia nigra, globus pallidus, basal ganglia)
5-HT1Da,b (Brain, Sumatriptan is partially selective agonist here)
5-HT1F (cortex, hippocampus)
Is prophylactic migraine therapy more effective in classic or common migraine?
How do prophylactic migraine therapies work?
Elevate CSD threshold and suppress CSD
What are the primary drugs used for migraine prophylaxis?
Beta-blockers (propranolol, timolol)
Anticonvulsants (valproate, topiramate)
What are contraindications of beta blockers?
Calcium channel blockers
What is the mechanism of valproate in migraine therapy?
Increases GABA-mediated neurotransmission
> suppresses inflammation and nociceptive transmission
Modulates 5-HT > suppresses rostral brain stem modulator
CSD likely suppressed by reduced glutamaergic activity
What is the mechanism of topiramate in migraine therapy?
Blocks sodium and calcium channels
Inhibits glutamate receptors
Enhances GABA activity
Inhibits activation of TNC
How many migraine days per month are needed before using BoTox for chronic migraine?
What is the mechanism of onabotulinum toxin?
Cleaves snares in release of CGRP from peripheral trigeminal sensory nerve terminals which :
1. mitigates development of peripheral sensitization
2. central sensitization
What drugs are good for treatment of acute migraine?
Mild to Moderate
- NSAIDs (naproxen), acetaminophen
- Metoclopramide (anti-emetic, typically used as adjuvant)
- Ergots (ergotamine, dihydroergotamine)
- Triptans (sumatriptan)
What is the mechanism of ergots (ergotamine, DHE)?
Non-selective 5-HT agonist at trigeminal nerves
How does DHE differ from ergotamine?
DHE has :
Fewer adverse effects
Parenteral administration (and nasal) for faster results
What drug interactions are there with ergots?
What is the mechanism of triptans (sumatriptan)?
Selective agonists at 5-HT1 receptors
What drugs should be avoided with triptans in order to reduce likelihood of catecholamine crisis?
Sumatriptan is a derivative of what?