Headache Drugs

NSAIDs
	
	Ibuprofen, naproxen, ketorolac
	MOA: anti-inflammatory (dec PGE synth, dec substance P) -> dec dural vasodilation
	1st line acute Rx for migraine
	PK: 10mg/kg advil (ibuprofen), 500mg aleve (naproxen)
	Tox: rebound HA in chronic use*, GI irritation

Caffeine
	
	MOA: vasoconstrictive
	1st line acute Rx for migraine
	Tox: rebound HA in chronic use, insomnia

Metoclopramide
	
	MOA: D2/5HT3 blocker (also muscarinic agonist -> Rx gastroparesis)
	1st line acute Rx for migraine in setting of emesis
	Tox: acute dystonia

-triptans
	
	7 agents: suma- (the original), zolmi-, ele-, riza-, almo-, nara-
	MOA: 5HT 1B/1D agonists (works at peripheral and 2nd order CN5 neurons), vasoconstrictive
	Acute Rx for migraine
	Choice based on speed, tolerability, sustained relief (ie half-life)
	PK: sumatriptan quickest onset but fast offset (t1/2 = 2hr), frova- and nara- longest t1/2

Ergotamines
	
	MOA: vasoconstriction of external carotid, 5HT/alpha-adr blocker
	Acute Rx for migraine
	Tox: nausea, vomiting, weakness, cramps, paresthesia, avoid in heart dz/HTN/pregnancy

Nonpharmacologic prophylaxis
	
	reassurance
	exercise
	adequate sleep
	avoid skipping meals and triggers
	biofeedback
	stress reduction techniques
	dietary interventions (MSG, caffeine, wine)
	psychologist/counseling

Cyproheptadine
	
	MOA: antihistamine, mild 5HT2 blocker
	Migraine prophylaxis in young children < 5yo
	Tox: sedation, appetite stimulant (weight gain)

Propranolol
	
	MOA: (anti-HTN) nonselective beta blocker -> inhibits NE release in locus ceruleus; modulate 5HT-?1A receptors
	Migraine prophylaxis
	Tox: asthma exacerbation due to beta blockade, hypotension, sedation, exercise intolerance

Verapamil
	
	MOA: (anti-HTN) Ca channel blocker
	Rx hemiplegic migraine (thought to be a Ca channelopathy)

Amitriptyline or nortriptyline
	
	MOA: (antidepressant) 5HT2 and NE blocker, probably GABA-B-R upregulation
	Migraine prophylaxis
	Tox: dry mouth, sedation, constipation, arrhythmias

SSRIs
	
	Fluoxetine, sertraline, paroxetine
	MOA: name says it all
	Migraine prophylaxis, weaker than amitriptyline

Valproic acid (depakote TM)
	
	MOA: (anticonvulsant) inc GABA, inhibits Ca channel, dec cortical excitability, dec 5HT dorsal raphe neuron activity
	Migraine prophylaxis
	PK: only migraine prophylaxis that can be given IV
	Tox: weight gain, teratogenic, hepatotox

Gabapentin (neurontin TM)
	
	MOA: (anticonvulsant) GABA analogue, modulates Ca channels
	Migraine prophylaxis, pretty safe agent
	PK: no interactions, no liver metabolism
	Tox: minimal (leg edema, sedation, weight gain)

Topiramate (topamax TM)
	
	MOA: Na & Ca channel, AMPA-kainate, GABA, and carbonic anhydrase blocker
	Migraine prophylaxis, Rx epilepsy
	Tox: cognitive slowing*, weight loss*, word-finding, kidney stones, dec sweating, kidney stones, glaucoma