Drugs for Migraine Flashcards
for migraines with mild to moderate symptoms, what are the first and second line options?
first line: simple analgesics (acetaminophen, acetaminophen-aspirin-caffeine)
second line (if inadequate response): NSAID-triptan combination (naproxen-sumatriptan)
for migraines with moderate to severe symptoms, what are the first (2) and second (3) line options?
first line: selective serotonin 1B/D receptor agonists (“-triptans”) or NSAID-triptan combination (naproxen-sumatriptan)
second line: CGRP antagonists (“-gepants”) or serotonin receptor 1F agonists (“-ditans”) or ergots (dihydroergotamine, ergotamine)
what is the general mechanism of acetaminophen (analgesic) and NSAIDs such as aspirin, naproxen, ibuprofen, and diclofenac in treating migraines?
inhibit prostaglandin synthesis —> prevent neuro-mediated inflammation in the trigeminovascular system
what are the adverse effects and contraindications (3) of acetaminophen (analgesic) and NSAIDs such as aspirin, naproxen, ibuprofen, and diclofenac?
GI adverse effects: dyspepsia, N/V, diarrhea
Renal adverse effects: hemodynamically-mediated AKI, acid-base disorders, acute interstitial nephritis
contraindications: previous ulcer disease, renal disease, aspirin hypersensitivity
what are 3 actions by which selective serotonin 5-HT(1B/D) receptor agonists (“-triptans”) treat migraines?
ex: sumatriptan, rizatriptan, zolmitriptan, eletriptan, almotriptan, naratriptan, frovatriptan
- normalization of dilated intracranial arteries via enhanced vasoconstriction
- inhibition of vasoactive CGRP (calcium gene-related peptide) release from perivascular trigeminal neurons
- inhibition of transmission through second-order neurons ascending to the thalamus
what is the clinical use of “-triptan” medications? what kind of drugs are these?
ex: sumatriptan, rizatriptan, zolmitriptan, eletriptan, almotriptan, naratriptan, frovatriptan
selective serotonin 5-HT(1B/D) receptor agonists
specifically treat migraines (first line for moderate-severe attacks)
basically vasoconstrict over-dilated intracranial arteries and inhibit transmission of neurons ascending to the thalamus (sensation)
what are the adverse effects and contraindications (3) of selective serotonin 5-HT(1B/D) receptor agonists (“-triptans”)?
ex: sumatriptan, rizatriptan, zolmitriptan, eletriptan, almotriptan, naratriptan, frovatriptan
treat mod-severe migraines
adverse: paresthesia, dizziness, somnolence, flushing, chest/neck tightness/pressure
contraindications: ischemic heart disease, uncontrolled HTN, cerebrovascular disease (agonists at coronary artery serotonin receptors!)
also should be avoided in patients receiving SSRI/SNRI antidepressants - risk of serotonin syndrome
what are 3 ways by which calcitonin gene-related peptide (CGRP) receptor antagonists (“-gepants”) treat migraines?
ex: ubrogepant, rimegepant, zavegepant, atogepant
- inhibition of exaggerated trigeminal pain signaling
- inhibition of trigeminal-mediated vasodilation
- inhibition of neurogenic inflammation in the trigeminovascular system
what kind of drugs are “-gepants,” and what is their clinical use?
ex: ubrogepant, rimegepant, zavegepant, atogepant
calcitonin gene-related peptide (CGRP) receptor antagonists
specifically treat migraines (second line for moderate-severe attacks, if “-triptans” fail)
basically inhibit overactivity of trigeminal nerve pain signaling/ vasodilation
what is the potential for drug-drug interactions with calcitonin gene-related peptide (CGRP) receptor antagonists (“-gepants”)?
ex: ubrogepant, rimegepant, zavegepant, atogepant
treat mod-severe migraines (2nd line)
potential interactions when administered alongside CYP3A modulators
safety in children has not been established
what are the 2 mechanisms by which serotonin 5HT(1F) receptor agonists (“-ditans”) such as lasmiditan treat migraines?
- inhibit exaggerated trigeminal pain signaling
- inhibit neurogenic inflammation in the trigeminovascular system
what kind of drugs are “-ditans” such as lasmiditan, and what are their clinical use?
serotonin 5HT(1F) receptor agonists
specifically treat migraines (2nd line for mod-severe attacks if inadequate response to “-triptans”)
basically block overactivity of trigeminal nerve pain signaling
lasmiditan should be avoided in patients receiving which type of antidepressant? why?
serotonin 5HT(1F) receptor agonists (“-ditans”) used to treat migraines
avoid in patients receiving SSRI or SNRI antidepressants due to risk of serotonin syndrome
what are 3 mechanisms by which ergots treat migraines?
ex: dihydroergotamine (DHE), ergotamine
nonselective serotonin 5-HT(1) receptor agonists
- normalization of dilated intracranial arteries via enhanced vasoconstriction
- inhibition of exaggerated trigeminal pain signaling
- inhibition of neurogenic inflammation in the trigeminovascular system
what kind of drug is dihydroergotamine (DHE), and what is it used to treat?
nonselective serotonin 5-HT(1) receptor agonist
treats mod-severe migraine attacks (2nd line, if inadequate response to “-triptans”)
limited use due to tolerability - N/V, chest tightness, diarrhea, paresthesia, muscle pain
what are 3 contraindications of dihydroergotamine (DHE) to treat migraines?
nonselective serotonin 5-HT(1) receptor agonist - basically vasoconstricts and blocks trigeminal overactivity
limited use due to tolerability - N/V, chest tightness, diarrhea, paresthesia, muscle pain
contraindications:
1. renal/hepatic failure
2. coronary/ cerebral vascular disease
3. uncontrolled HTN
name 2 beta blockers used for migraine prophylaxis - what are 3 potential adverse effects?
- propranolol
-
metoprolol
[3. timolol]
particularly useful in patients with comorbid HTN or angina!
adverse effects: dizziness/fatigue, cold hands/feet, insomnia/nightmares, ED
Name a tricyclic antidepressant (TCA) and a serotonin – norepinephrine reuptake inhibitor (SNRI) used for migraine prophylaxis
amitriptyline = TCA
venlafaxine = SNRI
mechanism independent of antidepressant activity, but useful in patients with comorbid depression/insomnia
adverse effects: dizziness, sedation, dry mouth, constipation, and difficulty urinating
what are 3 mechanisms by which anticonvulsants such as topiramate, divalproex, and valproate can be used for migraine prophylaxis?
- enhanced inhibitory GABA (y-aminobutyric acid) activity
- modulation of excitatory glutamate
- inhibition of Na+ and Ca2+ channel activity
useful in patients with comorbid seizure disorder or bipolar illness
name 2 anticonvulsants used for migraine prophylaxis
- topiramate [most commonly used, TOP of the list!]
-
divalproex
[3. valproate - risk of spina bifida]
adverse effects: paresthesia, somnolence, dizziness, diarrhea, weight loss, alopecia (divalproex), kidney stones (weak carbonic anhydrase inhibitors)
what kind of antibodies are galcanezumab, erenumab, fremanezumab, and eptinezumab? what are they used for?
anti-CGRP (calcitonin gene related protein) mAbs
used for migraine prophylaxis (for 4+ attacks/month), administered subcutaneously 1/month
name 2 anti-CGRP (calcitonin gene related protein) mAbs used for migraine prophylaxis
- galcanezumab
- erenumab
others: fremanezumab, eptinezumab
what is the name of the pharmaceutical botulin toxin used for migraine prophylaxis?
onabotulinumtoxin A (BoNTA)
cleaves SNAP-25 (synaptosomal-associated protein) to prevent synaptic vesicle fusion to neuronal cell membrane —> inhibits release of excitatory NT
used for migraine prophylaxis when attacks are 15+/month lasting for 4+ hours
which anti-convulsant should NOT be used in pregnant women to treat migraines, due to risk of neural tube defects (esp. spina bifida)?
valproic acid (valproate) - may also cause GI distress, tremor, hepatotoxicity (measure LFTs), weight gain
