Friday, 8-26-Migraines-Fitzpatrick

Question 1

NSAIDs and Acetaminophen are useful in treating this phase during a migraine attack:

Answer 1

Headache phase

Question 2

What are some beta-blocking preventive agents for tx of migraine? Ca channel blockers?

Answer 2

B blockers –> propanolol, timolol

Ca channel blockers –> verapamil

Given in the Asymptomatic phase

Question 3

In the Neurogenic inflammation theory of migraine, a wave of electrical activity and H+ and K+ passing through nerve cells stimulates the release of these neuropeptides ___ and these inflammatory mediators ___ that dilate cranial blood vessels and sensitive nerves to pain. Sensitization of nerves progresses from periphery to the brain

Answer 3

Neuropeptides=CGRP, Substance P

Inflamm mediators=NO, histamine, PG’s

Question 4

Neurogenic inflammation is stimulated by ___

Answer 4

CGRP (neuropeptide) and NO

Question 5

In the steps of Cortical Spreading Depression in migraines, step 1 involves brainstem dysfunction sparking a wave of excitation/depression in the cortex. Explain what happens to cerebral vasculature and the discharge from neurons:

Answer 5

Cerebral vasocontriction accompanied by H+, K+, NO discharge from neurons

Question 6

In the steps of Cortical Spreading Depression in migraines, step 2 involves electrolytes and NO diffusing and dilating cranial arteries and depolarize perivascular trigeminal terminals. What promote the neurogenic inflammation in this stage?

Answer 6

CGRP and neuropeptides

Step 3 includes Neurogenic inflammation irritating TG nerve and transmitting migraine pain

Question 7

These 2 key mediators interact throughout the trigeminal neurovascular system in migraines

Answer 7

CGRP and NO

Question 8

___ used to treat CAD can provoke migraine

Answer 8

Organic nitrates (NO)

Question 9

Cranial vessles and pre-synaptic TG nerve terminals express a distinc sub-set of 5-HT-1 receptors: Label the following:

Cranial vessels: __
Peripheral neuron: __
Central neuron: __

Answer 9

5HT-1B

5HT-1D

5HT-1B/1D

Question 10

___ are selective serotonin 5HT-1D/1B receptor agonists

Answer 10

Triptans

Question 11

Triptan binding to ___ receptor lowers cAMP, stimulates vasoconstriction (opposes vasodilation)

Answer 11

5HT-1B

Question 12

Triptan binding to ___ receptor on neurons lowers cAMP and inhibits pre-synaptic release of CGRP

Answer 12

5HT-1D

Question 13

Triptans have a high affinity for __ receptors located centrally in the region of the trigeminal nucleus caudalis in the brainstem. This modulates incoming painful sensory info from the periphery and inhibits upward transmission to the thalamus and higher brain centers where brain is perceived

Answer 13

5HT-1D

Question 14

What is the prototypical triptan? What is it metabolized by?

Answer 14

Sumatriptan (Imitrex)

Metabolized by Monoamine Oxidase-A (it is an indoleamine)

Question 15

These triptans have ~70% bioavailability and t1/2 of ~6 hrs

Answer 15

Almotriptan and Naratriptan

Question 16

This triptan drug is the active metabolite

Answer 16

Zolmitriptan

Question 17

These triptans show some evidence of better tolerance, claims of better efficacy (relative to sumatriptan)

Answer 17

Rizatriptan and Eletriptan

Question 18

This triptan has a t1/2 of ~24 hrs

Answer 18

Frovatriptan

Question 19

What are pros and cons of PO triptans?

Answer 19

Pros=easy to take

Cons=ineffective if vomit

Question 20

What are pros and cons of nasal spray triptans?

Answer 20

Pros=effective with nausea/vomiting, simple, works quickly

Cons=few triptans formulated as nasal sprays

Question 21

What are pros and cons of injectable triptans?

Answer 21

Pros=works quickly

Cons=inconvenient

Question 22

Which triptans have the most delivery options?

Answer 22

Sumatriptan –> injectable subQ, nasal spray, tablets

Zolmitriptan–> tablets, orally disintegrating tablets, nasal spray

Question 23

What are some contraindications for triptan usage?

Answer 23

Contraindicated in pts with a history or suspicion of ischemic or vasospastic coronary disease or other significant CV disorder and pts with uncontrolled HTN

Question 24

Sumatriptan, rizatriptan, and zolmitriptan are contraindicated in pts taking ____

Answer 24

MAO inhibitors –> They are metabolized by MAO

Question 25

This class of drugs are still used for severe or refractory migraine. They are less specific and interact with alpha receptors, dopamine receptors, various 5-HT receptors and exhibit mixed action at different receptors - agonist, partial agonist, antagonist

Answer 25

Ergot alkaloids --> dihydroergotamine and Ergotamine and caffeine (Cafergot)

Question 26

What are some ergot alkaloids?

Answer 26

Dihydroergotamine --> sublingual, intranasal, IV, IM, SC Ergotamine and caffeine (Cafergot) --> oral tablet, rectal suppository

Question 27

WHat should you never use a triptan with?

Answer 27

NEVER use a triptan and DHE together

Question 28

What are some side effects of ergot alkaloids?

Answer 28

- poisons/drugs of antiquity - strong emetic action is a major side effect - vasoconstriction is worse than that seen with triptans (Saint anthonys fire)

Question 29

When should you use the following for migraine tx in pregnancy: Aspirin: ___ Ibuprofen: __ Triptans: ___

Answer 29

Aspirin-1st, 2nd trimesters only Ibuprofen-1st, 2nd trimesters only Triptans-cautiously

Question 30

What migraine tx drugs are contra-indicated in pregnancy?

Answer 30

Dihydroergotamine | Other ergot alkaloids (abortion risk)

Question 31

BOTOX cleaves SNAP-25 in motor neurons, which inhibits ___ release at the motor endplate

Answer 31

Ach

Question 32

This Ca channel blocker for migraine prevention is often a 1st choice because of a good side effect profile

Answer 32

Verapamil Normalizes vessel tone, lessens Ca-dependent vesicle fusion

Question 33

What beta blockers are FDA approved for migraine prevention?

Answer 33

Propanolol or Timolol ``` Anxiolytic action Decreases sympathetic activity Blunts cortical spreading depression Clinically effective in 60-80% pts Lower frequency of attacks by ~50% ```

Question 34

What is a contraindication for beta blocker use in migraine preventative tx?

Answer 34

Asthmatic pts

Question 35

These anti-epilepsy drugs are approved for and effective in migraine prevention in adults

Answer 35

Topirimate and valproate

Question 36

Triptans (5HT1B/1D) receptor agonists and Ergot alkaloids are useful for this phase of a migraine attack:

Answer 36

Prodrome phase