Migraine Pharmacology Flashcards
Ergot alkaloids used to in treatment of migraine
Dihydroergotamine (DHE)
Ergotamine + caffeine
Triptans used in the treatment of migraine
Sumatriptan Almotriptan Naratriptan Zolmitriptan Rizatriptan Eletriptan Frovatriptan
Beta blockers used in prevention of migraine
Propranalol
Timolol
Tricyclic antidepressants used in prevention of migraine
Amitriptyline
Imipramine
Anticonvulsants used for migraine prevention
Topiramate
Valproate
Calcium channel blocker used for migraine prevention
Verapamil
In what case is Botox considered as a therapeutic option for migraine?
Chronic migraine only — 15+ days/month with headache lasting 4+ hours/day in people age 18+
MOA of Botox used for treatment of chronic migraine
Botox neurotoxin cleaves SNAP-25 in motor neurons which inhibits ACh release at the motor endplate —> reduced muscle activity
Migraines are considered neurovascular headaches in that neural events result in _____ of blood vessels resulting in pain and further nerve activation
The meninges sense pain due to their innervation by _____ axons
Vasodilation; trigeminal
During a migraine headache, mediators are released which potentiate the disease process.
______ is released from trigeminal Ad-fibers which increases dural vessel vasodilation
____ and ____ are released from trigeminal C-fibers and increase dural vessel permeability
CGRP
Substance P; neurokinin A
Why might organic nitrates (NO— used to treat coronary artery disease) provoke migraine?
NO causes release of CGRP in vessels and nerves
During a migraine, brainstem dysfunction sparks a wave of excitation and depression in the cortex termed _______ ______ ______, which leads to cerebral _________
This process is accompanied by H+, K+, and NO discharge from neurons
Cortical spreading depression (CSD); vasoconstriction
Cranial vessels and presynaptic trigeminal nerve terminals express a subset of _____ receptors, which modulate the actions of CGRP. _____ are selective agonists at these receptors (specifically ____ and _____), making them more effective than ergot alkaloids
Serotonin; Triptans; Vascular 5HT-1B; Synaptic 5HT-1D
Describe Triptans effects on binding to 5HT-1B receptors
Triptans binding to 5HT-1B receptors on vascular smooth muscle stimulates vasoconstriction of dilated meningeal, dural, and pial blood vessels
Describe Triptans effects on binding to 5HT-1D receptors
Triptans binding to 5HT-1D receptors on presynaptic nerve terminals inhibits presynaptic release of CGRP and other neuropeptides from the peripheral end of the trigeminal n.
Triptans binding to 5HT-1D receptors on trigeminal nucleus in the brainstem modulates incoming painful sensory info from the periphery, and inhibits upward transmission of painful sensory info to the thalamus and higher brain centers where pain is perceived
Sumatriptan has a half-life of 1-2 hours and is metabolized by _________
Monoamine oxidase A [thus it is contraindicated in those taking MAOIs]
Note that rizatriptan and zolmitriptan are also contraindicated in those taking MAOIs
______ is a triptan that is considered a prodrug, its active metabolite is a 5HT-1D agonist
Zolmitriptan
____ and ____ are triptans with some evidence of better tolerance and claims of better efficacy relative to sumatriptan
Rizatriptan; eletriptan
Which triptan would you choose for longest duration of migraine pain relief?
Frovatriptan — longest half life ~24 hrs
Which triptan would you choose for the most immediate relief of migraine?
Sumatriptan subcutaneous injection has fastest onset (works in 15 mins)
Could also use nasal spray of sumatriptan or zolmitriptan
[note that sumatriptan and zolmitriptan have the most options for delivery]
When choosing a triptan, why is it important to consider whether the patient is taking SSRIs, SNRIs, SDRIs, or linezolid (antibiotic - oxazolidinone)?
These patients would be put at higher risk for serotonin syndrome
All triptans are modest vasoconstrictors of coronary and renal vessels due to location of 5HT-1B/D receptors in smooth muscle. Given this, in what patient populations are triptans contraindicated?
Patients with hx or suspicion of ischemic or vasospastic coronary disease, or other significant cardiovascular disorder
Patients with uncontrolled HTN
Clinical manifestations of ergotism (ergot alkaloid toxicity)
Central: agitation, cerebrovascular ischemia, hallucinations, headaches, miosis, nausea, seizures, facial twitching, vomiting
Peripheral: bradycardia
Ischemic: angina, gangrene, hemorrhagic vesiculations and bullae, mesenteric infarction, myocardial infarction, renal infarction
What receptors does Dihydroergotamine bind to?
Binds various serotonin receptors non-selectively, as well as adrenergic and dopamine receptors
Also binds peripheral alpha1-adrenergic receptors in blood vessels
Effect of dihydroergotamine binding to peripheral alpha1-adrenergic receptors in blood vessels
Causes worse vasoconstriction when compared with triptans
Can lead to peripheral ischemia, vascular disease, acute coronary syndrome, and/or coronary vasospasm
Describe treatment of migraine during pregnancy
All trimesters: acetaminophen +/- codeine
First and second trimester only: aspirin, ibuprofen
Triptans are contraindicated
DHE and other ergot alkaloids are contraindicated (abortion risk)
Effective prophylactic treatment in migraine used in patients who fail triptan therapy; contraindicated in pregnant women because it likely causes decreased IQ scores in children born from women using this drug
Valproate
Beta blockers for migraine prevention are contraindicated in what patient population?
Asthma patients (due to SE of bronchoconstriction)
