Migraine Pharmacology

Question 1

Ergot alkaloids used to in treatment of migraine

Answer 1

Dihydroergotamine (DHE)

Ergotamine + caffeine

Question 2

Triptans used in the treatment of migraine

Answer 2

Sumatriptan
Almotriptan
Naratriptan
Zolmitriptan
Rizatriptan
Eletriptan
Frovatriptan

Question 3

Beta blockers used in prevention of migraine

Answer 3

Propranalol

Timolol

Question 4

Tricyclic antidepressants used in prevention of migraine

Answer 4

Amitriptyline

Imipramine

Question 5

Anticonvulsants used for migraine prevention

Answer 5

Topiramate

Valproate

Question 6

Calcium channel blocker used for migraine prevention

Answer 6

Verapamil

Question 7

In what case is Botox considered as a therapeutic option for migraine?

Answer 7

Chronic migraine only — 15+ days/month with headache lasting 4+ hours/day in people age 18+

Question 8

MOA of Botox used for treatment of chronic migraine

Answer 8

Botox neurotoxin cleaves SNAP-25 in motor neurons which inhibits ACh release at the motor endplate —> reduced muscle activity

Question 9

Migraines are considered neurovascular headaches in that neural events result in _____ of blood vessels resulting in pain and further nerve activation

The meninges sense pain due to their innervation by _____ axons

Answer 9

Vasodilation; trigeminal

Question 10

During a migraine headache, mediators are released which potentiate the disease process.

______ is released from trigeminal Ad-fibers which increases dural vessel vasodilation

____ and ____ are released from trigeminal C-fibers and increase dural vessel permeability

Answer 10

CGRP

Substance P; neurokinin A

Question 11

Why might organic nitrates (NO— used to treat coronary artery disease) provoke migraine?

Answer 11

NO causes release of CGRP in vessels and nerves

Question 12

During a migraine, brainstem dysfunction sparks a wave of excitation and depression in the cortex termed _______ ______ ______, which leads to cerebral _________

This process is accompanied by H+, K+, and NO discharge from neurons

Answer 12

Cortical spreading depression (CSD); vasoconstriction

Question 13

Cranial vessels and presynaptic trigeminal nerve terminals express a subset of _____ receptors, which modulate the actions of CGRP. _____ are selective agonists at these receptors (specifically ____ and _____), making them more effective than ergot alkaloids

Answer 13

Serotonin; Triptans; Vascular 5HT-1B; Synaptic 5HT-1D

Question 14

Describe Triptans effects on binding to 5HT-1B receptors

Answer 14

Triptans binding to 5HT-1B receptors on vascular smooth muscle stimulates vasoconstriction of dilated meningeal, dural, and pial blood vessels

Question 15

Describe Triptans effects on binding to 5HT-1D receptors

Answer 15

Triptans binding to 5HT-1D receptors on presynaptic nerve terminals inhibits presynaptic release of CGRP and other neuropeptides from the peripheral end of the trigeminal n.

Triptans binding to 5HT-1D receptors on trigeminal nucleus in the brainstem modulates incoming painful sensory info from the periphery, and inhibits upward transmission of painful sensory info to the thalamus and higher brain centers where pain is perceived

Question 16

Sumatriptan has a half-life of 1-2 hours and is metabolized by _________

Answer 16

Monoamine oxidase A [thus it is contraindicated in those taking MAOIs]

Note that rizatriptan and zolmitriptan are also contraindicated in those taking MAOIs

Question 17

______ is a triptan that is considered a prodrug, its active metabolite is a 5HT-1D agonist

Answer 17

Zolmitriptan

Question 18

____ and ____ are triptans with some evidence of better tolerance and claims of better efficacy relative to sumatriptan

Answer 18

Rizatriptan; eletriptan

Question 19

Which triptan would you choose for longest duration of migraine pain relief?

Answer 19

Frovatriptan — longest half life ~24 hrs

Question 20

Which triptan would you choose for the most immediate relief of migraine?

Answer 20

Sumatriptan subcutaneous injection has fastest onset (works in 15 mins)

Could also use nasal spray of sumatriptan or zolmitriptan

[note that sumatriptan and zolmitriptan have the most options for delivery]

Question 21

When choosing a triptan, why is it important to consider whether the patient is taking SSRIs, SNRIs, SDRIs, or linezolid (antibiotic - oxazolidinone)?

Answer 21

These patients would be put at higher risk for serotonin syndrome

Question 22

All triptans are modest vasoconstrictors of coronary and renal vessels due to location of 5HT-1B/D receptors in smooth muscle. Given this, in what patient populations are triptans contraindicated?

Answer 22

Patients with hx or suspicion of ischemic or vasospastic coronary disease, or other significant cardiovascular disorder

Patients with uncontrolled HTN

Question 23

Clinical manifestations of ergotism (ergot alkaloid toxicity)

Answer 23

Central: agitation, cerebrovascular ischemia, hallucinations, headaches, miosis, nausea, seizures, facial twitching, vomiting

Peripheral: bradycardia

Ischemic: angina, gangrene, hemorrhagic vesiculations and bullae, mesenteric infarction, myocardial infarction, renal infarction

Question 24

What receptors does Dihydroergotamine bind to?

Answer 24

Binds various serotonin receptors non-selectively, as well as adrenergic and dopamine receptors

Also binds peripheral alpha1-adrenergic receptors in blood vessels

Question 25

Effect of dihydroergotamine binding to peripheral alpha1-adrenergic receptors in blood vessels

Answer 25

Causes worse vasoconstriction when compared with triptans

Can lead to peripheral ischemia, vascular disease, acute coronary syndrome, and/or coronary vasospasm

Question 26

Describe treatment of migraine during pregnancy

Answer 26

All trimesters: acetaminophen +/- codeine

First and second trimester only: aspirin, ibuprofen

Triptans are contraindicated

DHE and other ergot alkaloids are contraindicated (abortion risk)

Question 27

Effective prophylactic treatment in migraine used in patients who fail triptan therapy; contraindicated in pregnant women because it likely causes decreased IQ scores in children born from women using this drug

Answer 27

Valproate

Question 28

Beta blockers for migraine prevention are contraindicated in what patient population?

Answer 28

Asthma patients (due to SE of bronchoconstriction)