migraine and migraine therapeutics Flashcards

1
Q

what is a primary headache vs secondary

A

primary headaches not caused by another medical conditions
secondary headaches are caused by problems elsewhere

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2
Q

types of primary

A

migraine, tension type, cluster

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3
Q

impact of migraines

A

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

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4
Q

what is the classification of episodic migraine and chronic migraine

A

occurs less than 15 days a month
chronic occurs more than 15

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5
Q

migraines can be divided into two major sub-types

A

migraines without aura
more common, higher attack freq,

migraines with aura
additionally have visual/sensory disturbances

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6
Q

diagnosis criterion for migraine

A

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

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7
Q

diagnosis criterion for migraine with aura

A

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

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8
Q

complications of migraines

A

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

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9
Q

what triggers migraine attacks?

A

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

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10
Q

describe the pathophysiology

A

complex genetic disorder
polygenic multifactorial inheritance

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11
Q

current migraine theory

A

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

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12
Q

trigeminovascular pain pathway

A

into (afferent) pathways
peripheray > trigeminal ganglion > trigemnnial nucles caudalis > brain
signals processed
out of (efferent modulatory) pathways
brain area processed > caudalis

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13
Q

what is cortical spreading depression?

A

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

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14
Q

what is first line treatment? acute migraines

A

aspirin 900mg, ibuprofen 400mg if ineffective incr to 600mg

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15
Q

when are triptans used?

A

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

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16
Q

5-ht and migraines

A

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

17
Q

triptans as receptor agonists

A

5ht subtype receptor agonists, activate the receptor
e.g samatriptan

18
Q

MoA of triptans

A

serotonin receptor subtypes 1B/D will constrict cranial arteries, NO is released during migraine attack, causing dilation - drug constricts arteries combating these effects

19
Q

disadvantages of triptans

A

contra-indicated in patients with coronary or cardiovascular disease, hypertension/pregnant
overuse can cause severe rebound attacks

20
Q

when should prophylactic treatment be used? describe

A

for patients suffering 4+ attacks per month
preventive medications aimed to reduce freq,severity+length of migraines
incr effectiveness of symptom relieving medicines

21
Q

give examples of prophylactic treatment medication and briefly how they work: beta blockers

A

beta blockers e.g. propanolol 80-160mg daily, unclear on how works, cause dilation of blood vessels

22
Q

give examples of prophylactic treatment medication and briefly how they work: topiramate

A

topiramate 50-100mg daily, blocks voltage dependent sodium and calcium channels; moa for migraine unclear

23
Q

give examples of prophylactic treatment medication and briefly how they work: tricyclic anti depressants

A

e.g. amitriptyline 25-150mg, prevents re-uptake of 5-HT and antagonising 5-HT2 receptors

24
Q

give examples of prophylactic treatment medication and briefly how they work: anti convulsants

A

e.g. sodium valporate 400-1599mg daily, voltage dependednt sodium channels

25
Q

give examples of prophylactic treatment medication and briefly how they work: candersartan

A

16mg daily, angiotensin 2 receptor antagonist

26
Q

recommended for prophylactic treatment of chronic migraine

A

botulinum toxin A, medication overuse has been addressed and patients have been appropriately treated with three or more oral migraine prophylactic treatments.

27
Q

calcitonin gene related peptide, describe

A

CGRP is a long amino acid, potent vasodilator, involved in neurogenic inflamm and nociception
increased levels of cgrp during attacks, all present at sites of body relevant to migraine,

28
Q

what is CGRP made up of?

A

calcitonin receptor like receptor (CLR) and receptor activity modifying protein 1 (ramp1) come together at the cell surface and create high affinity CGRP receptor

29
Q

what is CGRP made up of?

A

calcitonin receptor like receptor (CLR) and receptor activity modifying protein 1 (ramp1) come together at the cell surface and create high affinity CGRP receptor

30
Q

where are CGRP receptors present?

A

CNS, released by neurons, glial cells, ganglion,
periphery SMC, release of cgrp by neurons cause muscles to relax
also in mast cells, important regulation in inflamm

31
Q

how are monoclonal antibodies used to treat migraines

A

two targets, CGRP receptor and CGRP ligand molecule
companies have developed anti CGRP antibodies, binding to recpeotr/agonist and prevents activation,

32
Q

what are disadvantages of MAB used for migraines

A

injecting antibodies, reduce adherence
antibodies must be fully human

33
Q

what are preventative treatments for episodic and chronic migraines?

A

Erenumab, CGRP receptor
Galcanezumab, CGRP ligand
Fremanezumab, CGRP ligand
Eptinezumab, CGRP ligand

34
Q

what is the current status for treatments of acute migraine

A

GEPANTS (cgrp receptor antagonists)
ubrogepant (ubrelvy)
rimegepant (nurtec odt)
atogepant

DITANS (5-HT1f receptor agonists)
lasmiditan

both acute (abortive) treatments

35
Q

what is the current status for treatments of acute migraine

A

GEPANTS (cgrp receptor antagonists)
ubrogepant (ubrelvy)
rimegepant (nurtec odt)
atogepant

DITANS (5-HT1f receptor agonists)
lasmiditan

both acute (abortive) treatments