migraine

acute tension h/a treatment

NSAIDs

muscle relaxants/analgesics (carisoprodol, orphenadrine, chlorzoxazone, methocarbamol, cyclobenzabrine, metaxalone, baclofen)

chronic treatment of tension h/a

NSAIDs

TCAs/SSRIs

headache involvement of neuropeptides

neuropeptides (Calcitonin gene-related peptide, neurokinin A, substance P) are released from peripheral neurons causing sensitization of neurons and dilation of blood vessels

involvement of 5HT in h/a

can cause both vasoconstriction and vasodilation

activation of 5HT2 receptors on large vessels (arteries and veins) = constriction

activation of 5HT2 receptors on arterioles= dilation (by acting on endothelial cells to release NO)

activation of 5HT1 receptors on intracranial vessles = vasoconstriction

cluster h/a characteristics

generally last 30-45min (but can last a few hrs)

no known genetic link

histamine may cause but anti histamines are not helpful

1-4 h/a a day during cluster period of 1-2wks, then several weeks without

usually occur late @ night or early am, more common in spring/fall therefore often mistaken as allergies

acute cluster h/a treatment

dihydroergotamine, sumatriptin, lidocaine

preventative cluster h/a treatment

verapamil, prednisone, ergotamine, lithium

orphenadrine moa

anti cholinergic anti histamine

baclofen moa

agonist at GABA B

lidocaine moa in h/a

block AP in neuronsv

verapamil moa in h/a

L type CCB

block Ca channels and propogation of action potentials in nervous system, and decreases excitation of the brain overall, stopping triggering of a h/a

lithium moa h/a

IP3 signalling, unknown

hormonal h/a

caused by hormone fluctuations

OCs, pregnancy

organic h/a

caused by tumor, meningitis

sinus h/a

caused by sinus blockages (ex: from infection)

rebound h/a

caused by overuse of meds

does migraine have genetic link

yes 90% do

migraine personality

yype type A high stress people like Julius Caesar and Charles Darwin more likely potentially

age of onset of migraines

can start in childhood but often not til age 20-30yrs or age

IHS diagnostic criteria for migraine

episodic attack lasting 4-72hr with 2 of the following:

unilateral pain

throbbing

aggravation on movement

pain of moderate-severe intensity

and one of the following:

nausea or vomiting

photo or phonophobia e

explain aura and cortical spreading depression

1/3 of patients get

could be sx like nausea, tingling

often get development of scotoma- disruption of visual field (not feeling pain yet but is a sx the h/a is coming)

cortical spreading depression- decreased electrode activity across the brain, starting in PFC and spreads to the back of the brain. once it reaches brain sterm h/a is triggered and start feeling pain

dilation of blood vessels in pre headache phase vs in migraine

pre headache: likely constriction of blood vessels

blood vessels dilate and that is beginning of migraine

cranium/meninges involvement in migraine

cranium and meninges is area with all the blood vessels and nerves

if h/a is triggered(w no aura) get initial constriction than sudden dilation and release of inflammatory mediators/neuropeptides (SP, NKA, CGRP)

info then travels to brain stem and to tri geminal nerve and gives info to the brain that there is pain

cortical spreading depression involvement in pathophys of migraine

as cortical spreading depression moved across brain get changes in: arachadonic acid, K, NO, protons

gets to brain stem eventually and triggers h/a

how does eating things like cheese/wine cause migraine

brainstem has blood flow and monitors whether or not something in the blood is toxic

ex: opiates may cause vomiting bc brain stem senses them as toxic and wants it out of stomach

this is likely what brain is doing if someone is sensitive to types of food w/ migraine, blood flow goes by brain stem then TGN gets activated and get process initiated in meninges which feeds back down to brain and feel pain

ex of acute migraine treatments

NSAIDs (@ v high doses)- ibuprofen, ASA, naproxen, acetaminophen

erogt derivatives (5HT1 agonists); ergotamine, dihydroergotamine

triptans: sumatriptin, naratriptan, zolmitriptan, rizatriptan, almotriptin, eletriptin, frovatriptan

opiates- codeine

moa of triptans

triptans bind to 5HT1B as an agonist in vessels and cause constriction

triptans bind to 5HT1D as an agonist in peripheral neurons to decrease the release of CGRP, SP, NKA which shuts down neuronal pain sensitization in the meninges

agonist of 5HT1B/1D/1F in the trigeminal nerve and decrease excitability of neuron

advantages and disadvantages of ergot derivates

advantages: low cost and long time use

disadvantages: potent vasoconstrictor, rebound h/a, GI problems (more ae)

triptans advantages and disadvantages

advantages: less ae, more selective, good oral bioavailability (time to maximal conc is 1-4hr)

disadvantages: cost, CI in individuals with CVD

lasmiditan

serotonin receptor agonist that selectively binds to 5HT1F receptor (binding is most specific to TGN which decreases firing and causes vasoconstriction)

atogepant, rimegepant, ubrogepant moa

CGRP receptor antagonists

bind to CGRP receptor and block it so CGRP cant bind and cause dilation = decreased neurological inflammation

pros of lasmiditan and CGRP antagonists

less ae than other drugs (including triptans)

prophylactic migraine Tx ex

NSAIDs

B blockers (propranolol, timolol, metoprolol)

Ca channel blockers (verapamil, diltiazem, nicardipine, nifedipine, nimodipine)

methylsergide

anti depressants (TCA, SSRI)

anti epileptics (VPA, gabapentin)

corticosteroids (dexamethasone)

opiates (codeine and derivatives)

feverfew (parthenolide)

cyproheptadine

clonidine

proposed mechanism of genetic predisposition

alteration in gene for Ca channels = more susceptible to h/a

methysergide Moa

5ht2 antagonist- stopping initial constriction that triggers headache, keeping balance of extent of dilation

how does feverfew help h/a

parthenolide in fever few- works on 5HT receptors

cyproheptadine moaa

antihistamine

clonidine moa

alpha 2 agonist