Migraine

Question 1

What are the 4 stages of migraine?

Answer 1

1) Prodromal phase (warning signs) - some patients
2) Aura: 1 in 3 patients
3) Headache (+ other symptoms)
4) Sleep

Question 2

What is the term for Migraine with aura

Answer 2

“Classic” migraine

Question 3

What are the 3 characteristics of a classic migraine?

Answer 3

Less common
Two or more headaches preceded by aura
Aura symptoms:
  - blurred vision
  - flashing lights/zig-zag
  - missing area of visual field ("scotoma")

Question 4

What are the 2 characteristics of aura symptoms?

Answer 4

Fully reversible (within an hour)
Start at most 30 minutes before pain

Question 5

What are the 3 characteristics of Migraine without aura?

Answer 5

Lasts 4-72 hrs
At least two of:
  - unilateral
  - pulsating
  - moderate/severe intensity
  - aggravated by physical activity
At least one of:
  - nausea
  - vomiting 
  - photophobia
  - phonophobia

Question 6

Migraine is more common in _____ (women / men)

Answer 6

Women

Question 7

Why is migraine one of the most disabling disorders (*WHO)

4 symptoms

Answer 7

• Quadriplegia
• Psychosis
• Dementia
• Migraine

Question 8

What are 3 prophylactic drugs for migraine?

Answer 8

• Propranolol (beta blockers)
• Valproate
• Imipramine (Tricyclic “Antidepressants”)

These drugs are “successful” in that they prevent 50% of attacks. None is the best in terms of adverse effects (propranolol and Valproate is probably best)

Question 9

What is the most common prophylactic drug?

Answer 9

Propranolol

Question 10

True/False? Most Prophylactic drugs have several molecular targets

Answer 10

True

Question 11

What are the main adverse effects of Propranolol?

Answer 11

Contraindicated where beta block causes problems

Question 12

What are the main adverse effects of Valproate?

Answer 12

Thinning hair, fetal malformations

Question 13

What are the main adverse effects of TCAs?

Answer 13

eg. alcohol interaction and OD risk

Question 14

What are the main adverse effects of Topiramate?

Answer 14

Paresthesias (Tingling, pins & needles)

Question 15

What is an abortive drug?

Answer 15

A drug used to acutely treat migraine attacks?

Question 16

What are the 3 types of abortive drugs for migraine learned in class?

Answer 16

NSAIDs, Narcotic Analgesics, and 5-HT agonists

Question 17

What is often given with NSAIDs when treating migraine?

Answer 17

anti-emetics

Question 18

What is the only disadvantage of Narcotic analgesics as an abortive drug for migraine

Answer 18

Abuse

Question 19

What are the 2 main types of 5-HT agonists for treatment of migraine?
Are they preferred over other migraine drugs? Which is used more?

Answer 19

Ergotamine, dihydroergotamine (ergot derivatives)
Triptans (____-triptan)

Triptans are more effective with fewer side effects
Mainstay for moderate-severe migraine

Question 20

True/False? Ergot derivatives are pharmacologically richer and are more effective with fewer side effects than triptans

Answer 20

False, just richer

Question 21

What was the prototype triptan?

Answer 21

Sumatriptan

Question 22

True/False, the preferred route of administration for sumatriptan is oral because it provides relief sooner

Answer 22

False, much slower than subcutaneous but easier

Question 23

True/False? sumatriptan is better than ergotamine, and better than ergotamine + caffeine

Answer 23

True

Question 24

Why is caffeine administered with ergotamine?

Answer 24

Caffeine increases GI absorption of ergotamine by complexing with it

Question 25

True/False? sumatriptan only works for headache symptoms

Answer 25

False, works for nausea and sensitivity to light/sound

Question 26

Adverse effects of ergot-derived drugs and triptans?

Answer 26

Both are vasoconstrictive, ergots cause mental disturbance and triptans cause myocardial ischemia (constricts coronary arteries)

Question 27

List the meninges in order of increasing proximity to the brain

Answer 27

dura mater arachnoid (subarachnoid space) Pia mater

Question 28

List the evidence (3) for Wolff's Vasodilation hypothesis

Answer 28

- Pain pulsates like vessels - Vascular disease patients often suffered from headache - pain from: - stimulation of meningeal vessels - nitroglycerin (vasodilator) - angioplasty (dilating vessels)

Question 29

What is Wolff's vasodilation hypothesis for the mechanism of a headache?

Answer 29

Some trigger ends up triggering vasodilation, and this is sensed by the NS causing pain

Question 30

What are the 5 cracks in Wolff's vasodilation hypothesis?

Answer 30

- vessel does not pulsate (as much as he thought) - vascular disease - more than vascular? - vasoconstriction in migraine? - vasodilation and pain have different pain courses - angioplasty dilates but also scrapes, and is usually not painful anyway

Question 31

What is the dominant hypothesis for the mechanism of action of migraine and what is the mechanism?

Answer 31

Neurogenic inflammation: | Trigger causes neurogenic inflammation, which causes vasodilation and also pain (the two are unrelated)

Question 32

How is pain produced according to the neurogenic inflammation hypothesis?

Answer 32

A trigger depolarizes the nerve terminals of the trigeminal terminal The action potential rides up the CNS and is interpreted as pain (releases neuropeptides which cause pain)

Question 33

How is inflammation produced according to the neurogenic inflammation hypothesis?

Answer 33

A trigger depolarizes the nerve terminals of the trigeminal terminal Neuropeptides released from this act on inflammatory cells of the immune system IC release inflammatory mediators, which cause edema and plasma extravasation Inflammatory mediators act on nerve terminal making them more sensitive (+ve feedback)

Question 34

What is the name of the fibers that innervate vessels?

Answer 34

C-fibres

Question 35

How can we measure inflammation in a patient?

Answer 35

CGRP (a vasodilator) can be detected in plasma mast cells release cytokine, eicosanoids, histamine

Question 36

True/False? the sensory neurons on a rat brain's transverse sinus are ipsilateral

Answer 36

True

Question 37

Why might inflammation cause pain?

Answer 37

Terminal ganglion cells respond to "inflammatory soup" and cause pain

Question 38

True/False? inflammatory soup can make the dura more sensitive to forces

Answer 38

True (10x)

Question 39

What are the 3 types of 5-HT receptor?

Answer 39

5-HT1 5-HT2 5-HT3

Question 40

What are 3 subtypes of 5-HT1 receptor?

Answer 40

5-HT1A 5-HT1B 5-HT1D

Question 41

Which of the 3 5-HT1 receptor subtypes are important for drugs that are abortive to migraine?

Answer 41

5-HT1B 5-HT1D (drugs are 5-HT agonists)

Question 42

Sumatriptan binds selectively to which receptors?

Answer 42

5-HT1B | 5-HT1D

Question 43

True/False? the Ki of a drug is proportional to its abortive effectiveness

Answer 43

True

Question 44

Why does "ergot" have a richer pharmacology?

Answer 44

It has high affinity for many things

Question 45

Can sumatriptan cross the blood brain barrier? Why is that important?

Answer 45

No, and that helps narrow the search for sites of action

Question 46

Neurogenically-mediated CGRP release is ________ by sumatriptan

Answer 46

Inhibited

Question 47

Pain-associated neuronal activation in spinal cord ______ by sumatriptan

Answer 47

reduced

Question 48

What causes the progression of a migraine attack (with aura)?

Answer 48

Trigger in visual cortex, depolarizes meninges which propagates depolarization to everywhere Excess ions (K and H) stimulate nociceptors

Question 49

Does the spreading depression of a migraine correspond anatomically to the visual location of aura in humans?

Answer 49

Yes

Question 50

What causes scotoma and why doesn't every migraineur have scotoma?

Answer 50

The persistent depolarization of visual cortex neurons inactivates them, leading to scotoma We don't know why only some migraineurs experience scotoma