Migraine Flashcards
Migraine
severe, recurrent, unilaterial throbbing in temples, eye orbits, front of head, with nausea and vomiting
Required to terminate most migraine attacks
sleep
Symptoms of a migraine include
aura, photophobia, hyperacusis, polyuria, diarrhea, and disturbances in mood and appetite - may occur up to 24 hours before headache
Most common comorbidities of migraines
depression, anxiety disorders, stroke, irritable bowel syndrome, epilepsy, and hypertension
Migraine trigger factors
- Dietary factors
- Food additives
- Sleep disturbances
- Emotional factors
- Environmental factors
- Hormones cycles or changes
- Medication Use/Overuse/Withdrawal
- Excessive exercise
Migraine with Aura definition
- Minimum of 2 attacks
- Exhibits at least 3 of the following characteristics: gradual onset, mild to severe in intensity; reversible aura, lasts 5-60 min; headache follows aura within 60 min; may or may not have nausea and vomiting; photophobia, phonophobia
Migraine without aura definition
- Minimum 5 attacks lasting 4-72 hours (no aura, stars with headache
- Any 2 of: unilateral, pulsating, aggravated by routine physical activity, moderate to severe intensity
- Any 1 of: nausea and vomiting, photophobia and phonophobia
Migraine pathophysiology
Vasospasm of cerebral arteries - initial vasoconstriction, then vasodilation; sterile neurogenic perivascular edema and inflammation
Drugs that abort migraines are
vasoconstrictors
Cortical spreading depression
Elevates extracellular: K+, H+, NO, AA;
Activates TG nociceptors (afferents)
TG efferents release:
CGRP, substance P, NKA-
5-HT receptors
5-HT(1B), 5-HT(1D), and 5-HT(1F) receptors are highly expressed in the trigeminovascular system
5-HT(1B) receptors mediate
vasoconstriction
5-HT(1D) receptors likely inhibit
neurotransmitter release
5-HT(1F) receptors likely inhibit
release of nociceptive signaling molecules
Drugs used to abort migraines
- Acetominophen
- Aspirin/NSAIDs
- Serotonin (5-HT(1B/1D/1F)) agonists
Drugs used to prevent migraines
- beta-adrenergic antagonists
- Tricyclic antidepressants
- Anticonvulsants
- Botulinum Toxin A (Botox)
Nonspecific abortive agents
- Aspirin
- Acetaminophen (APAP)
- NSAIDs: ibuprofen, naproxen, ketoprofen, ketolorac
- Combination therapy with barbiturates, opiates
Excedrin Migraine
APAP 250 mg, ASA 250 mg, Caffeine 40 mg
combination therapy outperformed ibuprofen
Migralam
APAP 250 mg, Caffeine 100 mg, Isometheptene 65 mg
caffeine dose may cause insomnia
Midran
APAP 325 mg, dichlorophenazone 100 mg, isometheptene 65 mg
Fiorinal
butalbital 50 mg, aspirin 325 mg and caffeine 40 mg; with or without codeine 39 mg
FioricetR
butalbital 50 mg, APAP 325 mg and caffeine 40 mg; with or without codeine 30 mg
Butorphanol
nasal spray
Anti-emetics as adjuncts in migraine
Metoclopramide (ReglanR)
Metoclopramide (ReglanR)
Dopamine (D2) receptor antagonist; decreases nausea, stimulates gastric emptying, gastric emptying decreased in migraines, improves absorption of antimigraine agents
Source of ergot alkaloids
claviceps purpurea growing on rye
Contaminated rye flour caused
epidemics of ergot poisoning - gangrenous limbs, psychoses, spontaneous abortions
Ergot alkaloids
Ergonovine, serotonin, ergotamine
Ergot alkaloids used to abort migraines
Ergotamine and Dihydroergotamine (DHE)
Ergotamine and dihydroergotamine are
5-HT (2A/1B/1D/1F) receptor agonists and alpha1-adrenergic receptor agonists
Which ergot alkaloid is less prone to cause severe peripheral vasoconstriction with frequent dosing?
Dihydroergotamine (DHE)
How is DHE administered?
IM injection or nasal spray (poorly absorbed from GI tract)
How is Ergotamine administered?
Sublingual tablets (poorly absorbed from GI tract)
Most common toxic effects of ergots
- GI disturbances including diarrhea, nausea and vomiting
- Over-dosage particularly with ergotamine results in prolonged vasospasm
- Powerful uterine stimulants; contraindicated in pregnancy
Severe toxic effect of ergots
May result in gangrene and amputation of arms and legs
Drug-drug interactions with ergots
- HIV protease inhibitors and macrolides increase ergot levels
- beta blockers inhibit vasodilation (may cause gangrene)
- Dihydroergotamine decreases nitrate efficacy, i.e. decreased antianginal effects
5-HT (1B/1D/1F) receptor agonists
Serotonin and the “triptans”
Sumatriptan (Imitrex)
Synthetic 5-HT (1B/1D/1F) agonist; little peripheral effect; faster onset of relief than DHE; oral, nasal or subcutaneous routes of administration
Adverse effect of sumatriptan
higher incidence of headache recurrence with sumatriptan than with DHE
5-HT (1B/1D/1F) agonists slightly more efficacious and better tolerated than sumatriptan:
Zolmitriptan (Zomig); Naratriptan (Amerge); Rizatriptan (Maxalt); Almotriptan (Axert); Eletriptan (Relpax)
Naratriptan compared to sumatriptan
Naratriptan has slow onset, longer duration of action, lower incidence of recurrence than sumitriptan
Side effects of “triptans”
Mild and transient side effects: warmth and tingling, vertigo, malaise, fatigue, feelings of heaviness, sense of pressure in the chest
General contraindication for “triptans”
all triptans can precipitate angina; contraindicated in coronary artery disease (ischemic heart disease)
Contraindications for Sumatriptan (Imitrex)
increases bioavailability of MAO-A inhibitors; combined use is contraindicated
Contraindications for Naratriptan (Amerge)
Severe hepatic or renal impairment or peripheral vascular disease
Contraindications for Zolmitriptan (Zomig)
Patients with Wolff-Parkinson-White syndrome
Contraindications for Rizatriptan (Maxalt)
Contains phenylalanine; PKU patients beware (orally disintegrating tablets only)
Criterion for a refractory headache (Status Migrainosus)
headahce for >72 hours with or without treatment
Treatment for status migrainosus
Triptans
Treatment for status migrainosus if triptans fail
Sub-Q of DHE
+/- IM or IV narcotic
+/- corticosteroid
When should preventive meds be used for migraine headache?
- More than 2 moderate or severe headaches per month
- Abortive medications have failed to provide sufficient relief or are contraindicated
- Quality of life is significantly decreased due to the migraine severity and/or frequency
- You are willing to take daily medications, endure possible side effects, and change medications if necessary
1st line agents used to prevent migraines
- Beta-adrenergic receptor antagonists (propranolol and timolol)
- Topiramate
- Tricyclic antidepressants
- Valproic acid
MOA of OnabotulinumtoxinA (Botox)
Toxin heavy chains mediate uptake into nerve terminals via endocytosis; toxin light chains cleave SNAP25; NT release is inhibited
Cleaved SNAP15 co-localizes with
CGRP in the dura
Criteria for Botox use in chronic migraines
- 15 headache days/month for 3 months
2. Migraine medication overuse
What is calcitonin gene-related pepetide?
a 39 aa peptide and potent vasodilator
Where is CGRP released from
released from the trigeminal nerve in migraines
What does CGRP potentiate
potentiates the pain response
Potential alternative to triptans for patients sensitive to vasoconstrictors
antagonism of the CGRP receptor (effective in aborting migraines)
5-HT can inhibit
release of inflammatory neuropeptides such as substance P, neurokinin A, and CGRP from perivascular nerve terminals via 5-HT (1F) receptors
Lasmiditan
selective 5-HT (1F) agonist - in development
