migraine and migraine therapeutics Flashcards
what is a primary headache vs secondary
primary headaches not caused by another medical conditions
secondary headaches are caused by problems elsewhere
types of primary
migraine, tension type, cluster
impact of migraines
common disabling primary headache disorder
affects 1 in 7 people
43% women over lifetime, 18% men
affects people during most productive years
2.25billion costs in a year
very prevalent
maintained in gene pool
what is the classification of episodic migraine and chronic migraine
occurs less than 15 days a month
chronic occurs more than 15
migraines can be divided into two major sub-types
migraines without aura
more common, higher attack freq,
migraines with aura
additionally have visual/sensory disturbances
diagnosis criterion for migraine
at least 5 headache attacks lasting between 4-72 hours
two of the following characterictics,
1)unilateral location
2)pulsating quality
3)mod-severe pain intensity
4)aggravation by or causing avoidance of routine physical activity
during headache at least one of the following
1)nausea and/or vomiting
2)photophobia and phonophobia
diagnosis criterion for migraine with aura
at least 2 headache attacks lasting between 4-72 hours
must have no motor weakness and have aura consisting of
1)fully reversible symptoms incl. positive features e.g. flickering lights, spots, lines
2)fully … incl negative features e.g. loss of vision
3)fully …incl positive features e.g. pins and needles
4)fully … incl negative features e.g. numbness
5)fully reversible dysphasic speech
and at least 2 of
1)visual symptoms and/or unilateral sensory symptoms
2)at least one aura symptom develops gradually over 5 minutes and/or different aura symptoms occur in succession over 5 minutes
3)each symptom lasts more than 5 to 60 minutes
complications of migraines
1)status migrainosus
attack lasts over 72 hrs
2)migrainous infarction (stroke)
aura>1 hour, blood vessels narrow O2 drops
3)persistent aura without infarction
aura>1 week
4)migraine aura-triggered seizure
seizure follows a migraine
what triggers migraine attacks?
inherited tendency to headache and cannot be cured
can be modified and controlled by life-style adjustment and use of medicines
chco, alcohol, caffeine, late sleeping
describe the pathophysiology
complex genetic disorder
polygenic multifactorial inheritance
current migraine theory
migraine is a neurovascular disease,
occur by activation and sensitisation of the trigeminovascular pain pathway
innervates cranial tissues
“cortical spreading depression” is the neuro physical correlate of migraine aura
trigeminovascular pain pathway
into (afferent) pathways
peripheray > trigeminal ganglion > trigemnnial nucles caudalis > brain
signals processed
out of (efferent modulatory) pathways
brain area processed > caudalis
what is cortical spreading depression?
slowly propagating wave of depolarisation over neurons and glial cells, at a speed of 3-5mm/min
depolarisation leading to efflux of protons and potassium ions, NO and arachidonic acid and release of neuropeptides,
overall inflammation which lead to activation of neurons which turned into neurogenic inflammation
what is first line treatment? acute migraines
aspirin 900mg, ibuprofen 400mg if ineffective incr to 600mg
when are triptans used?
first line treatment acute migraines, sumatriptan 50-85 mg and naproxen 500 mg
often prescribed with anti emetics e.g. metoclopramide 10mg, prochlorperazine 10 mg
5-ht and migraines
levels of 5-ht decreased during attacks, discovery of it involved in pathophysiology of migraines
saw that slow IV of 5-ht could abort a migraine attack
triptans as receptor agonists
5ht subtype receptor agonists, activate the receptor
e.g samatriptan
MoA of triptans
serotonin receptor subtypes 1B/D will constrict cranial arteries, NO is released during migraine attack, causing dilation - drug constricts arteries combating these effects
disadvantages of triptans
contra-indicated in patients with coronary or cardiovascular disease, hypertension/pregnant
overuse can cause severe rebound attacks
when should prophylactic treatment be used? describe
for patients suffering 4+ attacks per month
preventive medications aimed to reduce freq,severity+length of migraines
incr effectiveness of symptom relieving medicines
give examples of prophylactic treatment medication and briefly how they work: beta blockers
beta blockers e.g. propanolol 80-160mg daily, unclear on how works, cause dilation of blood vessels
give examples of prophylactic treatment medication and briefly how they work: topiramate
topiramate 50-100mg daily, blocks voltage dependent sodium and calcium channels; moa for migraine unclear
give examples of prophylactic treatment medication and briefly how they work: tricyclic anti depressants
e.g. amitriptyline 25-150mg, prevents re-uptake of 5-HT and antagonising 5-HT2 receptors
give examples of prophylactic treatment medication and briefly how they work: anti convulsants
e.g. sodium valporate 400-1599mg daily, voltage dependednt sodium channels
