Migraine Drugs - Fitzpatrick Flashcards
CGRP
CSD
DHE
Calcitonin gene related peptide - neurotransmitter
Cortical-spreading depression
Dihydroergotamine
Typical prodrome symptoms before a migraine
When?
Yawning, depression, lethargy, excitability, craving, distaste
12-36 hours before
Typical acute migraine symptoms
Headache, Photophobia, Phobophobia, Nausea, Vomiting
Typical postdrome symptoms after a migraine
Exhaustion, fatigue
When does the aura come in (if present)?
Symptoms?
Between prodrome and headache
Flashing lights, deja vu, weird neurologic symptoms
3 groups of therapeutic migraine drugs (+ when they are administered)
Triptans - during prodrome phase
Ergot alkaloids - during prodrome phase
NSAIDs/acetaminophen - during headache phase
Other name for serotonin
Why is this useful to know?
5-HT = hydroxyTRIPTAmine
TRIPTANs = serotonin receptor 1B/1D agonists
4 groups of preventative migraine drugs (w/ drug names)
Given when?
Beta-blockers (propranolol, timolol)
Antidepressants (Tri-cyclic, SSRIs)
Anticonvulsants (valproate, topirimate)
Ca++ channel blockers (verapamil)
Asymptomatic phase (between attacks)
Describe the pathophysiology of a migraine
- Neural electric wave from periphery to TRIGEMINAL GANGLION/NERVE to brain causes CEREBRAL vessel vasoconstriction and release of CGRP, NO, Histamine, PGs release.
- Released NTs diffuse across and dilate CRANIAL blood vessels, and CGRP sensitizes nerves to pain.
- Neurogenic inflammation travels back to the Trigeminal ganglion to the Trigeminal nucleus, causing PAIN
A patient has coronary artery disease and is prescribed organic nitrates for treatment to dilate the vessels. What is a potential side effect of taking this drug?
MIGRAINES - N.O. is heavily involved in the pathophysiology
Where does serotonin come into play regarding migraines?
Cranial vessels possess 5HT-1B receptors.
Neurons possess 5HT-1D receptors (pre-synaptic).
The TG nucleus (CNS) has 5HT-1D receptor also.
Function of serotonin on vessels, nerves, and TG nucleus?
Vessels - causes vasoconstriction (opposses vasodilation)
Neuron terminals - inhibits CGRP release
TG nucleus - inhibits incoming pain sensations from reaching thalamus and higher brain, where pain is perceived
Sumatriptan benefit?
Half-life?
Clearance?
Sub-Q or Nasal Spray options (quicker and longer than oral)
Half-life = 1-2 hours
Metabolized by MOA
Contrast different Triptans (compare to Sumatriptan)
Naratriptan - Longer half-life, higher bioavailability
Zolmitriptan - has active metabolite
Frovatriptan - MUCH longer half-life (1 day)
Pro and Con of oral Triptan
Easy to take, but ineffective w/ vomiting
Pro and Con of nasal spray Triptan
Good, easy, and quick with nausea/vomiting, but few options available
Pro and Con of injection Triptan
Works quickly, but inconvenient to give shot every time
2 Triptans with most delivery options
Compare and contrast delivery options
Sumatriptan, Zolmitriptan
BOTH = Tablets and nasal spray Suma = Sub-Q injection Zolm = Orally-disintegrating tablets
If one Triptan does not work, should you quit them all?
NO
A patient needs a Triptan for migraines, and wants one that works the longest to prevent risk of overuse. Best option?
Frovatriptan
A patient needs a Triptan for migraines, and needs them to work fast. Best options?
Nasal spray (Suma, Zolm) or Sub-Q injection (Suma)
Contraindications to Triptan use
Ischemic/vasospastic coronary disease or other CV disorders
A patient needs a Triptan for migraines. She is currently taking a MAO inhibitor for depression. Which drugs should be AVOIDED?
Sumatriptan, Zolmitriptan, Rizatriptan
Why should MAO inhibitors and certain Triptans not be used together?
The Triptans (previous card) can be converted into an active metabolite that is then broken down by MAO. Inhibiting MAO will cause prolonged and toxic effects of the Triptan.
2 Ergot alkaloids
DHE, Ergotamine
Caution regarding ergot alkaloids?
Interact with serotonin receptors AND dopamine receptors AND alpha-adrenergic receptors. THUS –> can lead to a variety of side effects
DHE vs. Ergotamine/caffeine (Cafergot)
DHE - sub-lingual, intranasal, IV, IM, SC
Cafergot - oral, rectal
Contrast DHE vs. Triptans
Triptans - FASTER
DHE - LONGER
A patient is on a Triptan for migraines, but it doesn’t seem to be working well enough. What should you try?
What should you NOT do?
Why?
DHE instead
Do NOT use DHE + Triptan together
Both cause vasoconstriction
Side effects of ergot alkaloids (DHE)
Emesis (major), BAD vasoconstriction
Patient needs treatment for migraines. She has a present history of coronary artery disease. What should especially be avoided?
DHE
A pregnant woman presents with migraines. What are your treatment options?
What is especially contraindicated? Why?
Acetaminophen +/- codeine
Aspirin/Ibuprofen - 1st and 2nd trimesters
Triptans - CAUTIOUSLY
DHE/ergot alkaloids (vasoconstriction –> abortion)
Good drug COMBOS for migraine treatment
Triptan + NSAIDs/acetaminophen
- Sumatriptan + Naproxen (especially good)
Triptan + anti-emetic
DHE + anti-emetic
Function of BOTOX for migraines
Used when?
Inhibits ACh release at motor synapses
CHRONIC migraines, or nothing else works
Migraine prevention agent groups
Taken when?
Beta-blockers
TC antidepressants
Anticonvulsants
Ca++ channel blockers
Daily, when bad or chronic, when asymptomatic
1st choice for migraine prevention
Mechanism?
Verapamil (Ca++ channel blocker)
Prevents cerebral vasoconstriction and NT release –> prevent cranial vasodilation
A patient needs preventative treatment for migraines. She has a history of asthma. What is contraindicated?
Beta-blockers (due to bronchoconstriction)
Other side effects of beta-blockers
Typical anti-sympathetic stuff (fatigue, change of sexual function, lost exercise tolerance, hypotension/bradycardia)
Anti-epilepsy drugs used for migraine prevention
Mechanism?
Caution?
Topirimate, Valproate
Prevents that spread of electrical activity during seizure
SUICIDE RISK when not used for epilepsy/seizures
