Friday, 8-26-Migraines-Fitzpatrick Flashcards
NSAIDs and Acetaminophen are useful in treating this phase during a migraine attack:
Headache phase
What are some beta-blocking preventive agents for tx of migraine? Ca channel blockers?
B blockers –> propanolol, timolol
Ca channel blockers –> verapamil
Given in the Asymptomatic phase
In the Neurogenic inflammation theory of migraine, a wave of electrical activity and H+ and K+ passing through nerve cells stimulates the release of these neuropeptides ___ and these inflammatory mediators ___ that dilate cranial blood vessels and sensitive nerves to pain. Sensitization of nerves progresses from periphery to the brain
Neuropeptides=CGRP, Substance P
Inflamm mediators=NO, histamine, PG’s
Neurogenic inflammation is stimulated by ___
CGRP (neuropeptide) and NO
In the steps of Cortical Spreading Depression in migraines, step 1 involves brainstem dysfunction sparking a wave of excitation/depression in the cortex. Explain what happens to cerebral vasculature and the discharge from neurons:
Cerebral vasocontriction accompanied by H+, K+, NO discharge from neurons
In the steps of Cortical Spreading Depression in migraines, step 2 involves electrolytes and NO diffusing and dilating cranial arteries and depolarize perivascular trigeminal terminals. What promote the neurogenic inflammation in this stage?
CGRP and neuropeptides
Step 3 includes Neurogenic inflammation irritating TG nerve and transmitting migraine pain
These 2 key mediators interact throughout the trigeminal neurovascular system in migraines
CGRP and NO
___ used to treat CAD can provoke migraine
Organic nitrates (NO)
Cranial vessles and pre-synaptic TG nerve terminals express a distinc sub-set of 5-HT-1 receptors: Label the following:
Cranial vessels: __
Peripheral neuron: __
Central neuron: __
5HT-1B
5HT-1D
5HT-1B/1D
___ are selective serotonin 5HT-1D/1B receptor agonists
Triptans
Triptan binding to ___ receptor lowers cAMP, stimulates vasoconstriction (opposes vasodilation)
5HT-1B
Triptan binding to ___ receptor on neurons lowers cAMP and inhibits pre-synaptic release of CGRP
5HT-1D
Triptans have a high affinity for __ receptors located centrally in the region of the trigeminal nucleus caudalis in the brainstem. This modulates incoming painful sensory info from the periphery and inhibits upward transmission to the thalamus and higher brain centers where brain is perceived
5HT-1D
What is the prototypical triptan? What is it metabolized by?
Sumatriptan (Imitrex)
Metabolized by Monoamine Oxidase-A (it is an indoleamine)
These triptans have ~70% bioavailability and t1/2 of ~6 hrs
Almotriptan and Naratriptan
This triptan drug is the active metabolite
Zolmitriptan
These triptans show some evidence of better tolerance, claims of better efficacy (relative to sumatriptan)
Rizatriptan and Eletriptan
This triptan has a t1/2 of ~24 hrs
Frovatriptan
What are pros and cons of PO triptans?
Pros=easy to take
Cons=ineffective if vomit
What are pros and cons of nasal spray triptans?
Pros=effective with nausea/vomiting, simple, works quickly
Cons=few triptans formulated as nasal sprays
What are pros and cons of injectable triptans?
Pros=works quickly
Cons=inconvenient
Which triptans have the most delivery options?
Sumatriptan –> injectable subQ, nasal spray, tablets
Zolmitriptan–> tablets, orally disintegrating tablets, nasal spray
What are some contraindications for triptan usage?
Contraindicated in pts with a history or suspicion of ischemic or vasospastic coronary disease or other significant CV disorder and pts with uncontrolled HTN
Sumatriptan, rizatriptan, and zolmitriptan are contraindicated in pts taking ____
MAO inhibitors –> They are metabolized by MAO
This class of drugs are still used for severe or refractory migraine. They are less specific and interact with alpha receptors, dopamine receptors, various 5-HT receptors and exhibit mixed action at different receptors - agonist, partial agonist, antagonist
Ergot alkaloids –> dihydroergotamine and Ergotamine and caffeine (Cafergot)
What are some ergot alkaloids?
Dihydroergotamine –> sublingual, intranasal, IV, IM, SC
Ergotamine and caffeine (Cafergot) –> oral tablet, rectal suppository
WHat should you never use a triptan with?
NEVER use a triptan and DHE together
What are some side effects of ergot alkaloids?
- poisons/drugs of antiquity
- strong emetic action is a major side effect
- vasoconstriction is worse than that seen with triptans (Saint anthonys fire)
When should you use the following for migraine tx in pregnancy:
Aspirin: ___
Ibuprofen: __
Triptans: ___
Aspirin-1st, 2nd trimesters only
Ibuprofen-1st, 2nd trimesters only
Triptans-cautiously
What migraine tx drugs are contra-indicated in pregnancy?
Dihydroergotamine
Other ergot alkaloids (abortion risk)
BOTOX cleaves SNAP-25 in motor neurons, which inhibits ___ release at the motor endplate
Ach
This Ca channel blocker for migraine prevention is often a 1st choice because of a good side effect profile
Verapamil
Normalizes vessel tone, lessens Ca-dependent vesicle fusion
What beta blockers are FDA approved for migraine prevention?
Propanolol or Timolol
Anxiolytic action Decreases sympathetic activity Blunts cortical spreading depression Clinically effective in 60-80% pts Lower frequency of attacks by ~50%
What is a contraindication for beta blocker use in migraine preventative tx?
Asthmatic pts
These anti-epilepsy drugs are approved for and effective in migraine prevention in adults
Topirimate and valproate
Triptans (5HT1B/1D) receptor agonists and Ergot alkaloids are useful for this phase of a migraine attack:
Prodrome phase
