L21

Question 1

leading cause of disability worldwide,

particularly in those under 50

Answer 1

migraine

Question 2

primary__ disorder
characterized by recurring headaches
that are moderate to severe, pulsating
in nature, last from __hours

Answer 2

headache

2-72

Question 3

sensitivity to normal__ input

Answer 3

sensory

Question 4

aura

Answer 4

precedes migraine - 20%

visual disturbances consisting of flashing lights or zigzag lines moving across the field of vision

Question 5

migraine risk a mix of__ and__ factors
affects__ more than
men; increase after _

Answer 5

genetic environmental
women
puberty

Question 6

familial hemiplegic

migraines

Answer 6

weakness of half of the body

autosomal dominant inheritance

Question 7

3 known genetic mutations

associated with FHM:

Answer 7

• P/Q-type calcium channel
• Na+/K+ATPAase
• Na+ channel subunit

Question 8

thought to be driven by cortical

spreading depression:

Answer 8

wave of
neuronal depolarization followed
by desensitization (“depression”)
that propagates across the
cortex)

Question 9

mutations lower the threshold for

Answer 9

cortical spreading depression

Question 10

Trigeminal nerve is the

Answer 10

largest cranial nerve.

Question 11

Peripheral processes divided into three branches

Answer 11

• ophthalmic, maxillary and mandibular.

Question 12

3 purposes of Trigeminal System:
‣ Senses _ and _ in
the head region
‣ innervates the _ _
(membrane that surrounds the brain)
‣ controls _ blood vessels
(trigeminovascular system)

Answer 12

‣ Senses pain and temperature in
the head region
‣ innervates the dura mater
(membrane that surrounds the
brain)
‣ controls cerebral blood vessels
(trigeminovascular system)

Question 13

pain in head detected by _ branch of the _ nerve innervating _ mater and associated blood vessels

Answer 13

pain in head detected by ophthalmic branch of the trigeminal nerve innervating dura mater and associated blood vessels

Question 14

cause of migraine still unknown, but thought to be a__ disease

Answer 14

neurovascular

Question 15

why is migiraine thought to be neurovascular disease (3)

1. _ vessels _ during migraine attack
2. _ blood vessel stimulation provokes headache
3. _ drugs alleviate pain

Answer 15

1. extracerebral vessels dilate during migraine attack
2. cranial blood vessel stimulation provokes headache
3. vasoconstrictor drugs alleviate pain

Question 16

release of 5-HT leads to

Answer 16

vasoconstriction

Question 17

low _ levels in migraineurs_ attacks

Answer 17

5-HT

between

Question 18

5-HT is released_ migraine attacks

Answer 18

during

Question 19

Calcitonin gene-related peptide (CGRP) located in

Released from_ in response to_, leads to_

elevated/decreased in those with migraine

Answer 19

trigeminal peripheral afferents.

afferents, pain, vasodilation

elevated

Question 20

Treatment strategies incorporates both _ and_ strategies

Answer 20

prophylactic

abortive

Question 21

Prophylactic treatments are taken_ to_ attacks,

abortive treatments taken__ an attack_

Answer 21

daily, prevent

once, occurs

Question 22

Non-pharmacological Interventions:

Answer 22

Identify triggers (Diet, exercise, consistent sleep, avoiding excessive caffeine and alcohol, minimize stress).

Question 23

prophylactic Pharmacological Interventions: 
Beta blockers (_), anticonvulsants (_), antidepressants (_)

Answer 23

Beta blockers (propanolol) - decrease BP, anticonvulsants (gabapentin) - block pain, antidepressants (amitriptyline) - SSRI by blocking SERT

Question 24

abortive pmcol interventions
Non-specific analgesics (,,,)
risk of

Answer 24

asprin, acetaminophen, NSAID, opioids

medication overuse headache

Question 25

caffeine is an __ receptor antagonist • leads to __ • __ absorption of some __ (acetominophen, ergotamines) • improves migraine treatment during attack • but may also trigger __ or result in __ headache (withdrawal)

Answer 25

caffeine is an adenosine receptor antagonist • leads to vasoconstriction • increases absorption of some analgesics (acetominophen, ergotamines) • improves migraine treatment during attack • but may also trigger headaches or result in rebound headache (withdrawal)

Question 26

ergot alkaloid (like LSD) • first __ anti-migraine agents (introduced in 1926), but no longer first line therapy • agonists for ___receptors that inhibit neurogenic ___ • but, low degree of receptor ___ which increases the risk of experiencing a drug-induced __ __

Answer 26

``` ergot alkaloid (like LSD) • first specific anti-migraine agents (introduced in 1926), but no longer first line therapy • agonists for 5HT-1b/d receptors that inhibit neurogenic inflammation • but, low degree of receptor selectivity which increases the risk of experiencing a drug-induced side effect ```

Question 27

Ergotamine can produce coronary ___, often with associated ___ changes and __ pain in patients with coronary artery disease. • Contraindicated in patients with __ vascular disease, coronary heart disease, uncontrolled hypertension, stroke

Answer 27

Ergotamine can produce coronary vasoconstriction, often with associated ischaemic changes and anginal pain in patients with coronary artery disease. • Contraindicated in patients with peripheral vascular disease, coronary heart disease, uncontrolled hypertension, stroke

Question 28

Ergotamines Absorption+Distribution: Large first pass metabolism via ___ administration leads to ___ bioavailability (<1%), caffeine can improve both __ and __ of absorption

Answer 28

Large first pass metabolism via oral administration leads to low bioavailability (<1%), caffeine can improve both rate and extent of absorption

Question 29

Ergotamines | Metabolism: metabolized by __ by poorly defined enzymes. Half life is __hours

Answer 29

Metabolism: metabolized by liver by poorly defined enzymes. Half life is 2hours

Question 30

Ergotamines | Excreted in__

Answer 30

bile

Question 31

``` Triptans first line migraine therapy (i.e. ___) •selective 5-HT1b/d ___ •two mechanisms: ___ and inhibition of ___ nerve •avoids many of the side effects of __ ```

Answer 31

first line migraine therapy (i.e. Sumatriptan) •selective 5-HT1b/d agonist •two mechanisms: vasoconstriction and inhibition of trigeminal nerve •avoids many of the side effects of ergotamine

Question 32

Sumatriptan • Absorption+Distribution: Bioavailability around __% when taken orally, __% when given subcutaneously (because first pass metabolism) • Metabolism: metabolized by __ __ in the liver to __ acid. Half life around _hours. • Excretion: Cleared in the __.

Answer 32

* Absorption+Distribution: Bioavailability around 14% when taken orally, 96% when given subcutaneously (because first pass metabolism) * Metabolism: metabolized by monoamine oxidase in the liver to indoleacetic acid. Half life around 2 hours. * Excretion: Cleared in the urine.

Question 33

CGRP Antagonists small molecule CGRP __ • __ __s to CGRP or CGRP receptor • several potential drug candidates have been developed and currently under investigation

Answer 33

small molecule CGRP antagonists • monoclonal antibodies to CGRP or CGRP receptor • several potential drug candidates have been developed and currently under investigation

Question 34

CGRP Antagonists BIBN4096 (__) • Good __ at treating migraine • __ bioavailability (particularly orally) which limited clinical efficacy. Abandoned at Phase __ clinical trial.

Answer 34

BIBN4096 (Olcegepant) • Good efficacy at treating migraine • Poor bioavailability (particularly orally) which limited clinical efficacy. Abandoned at Phase II clinical trial.

Question 35

CGRP Antagonists MK-0974 (__) • several Phase __ clinical trials support anti-migraine efficacy and safety • problems emerged with __ dosing (elevation of liver __). Abandoned at Phase __ Clinical Trial.

Answer 35

MK-0974 (Telcagepant) • several Phase III clinical trials support anti-migraine efficacy and safety • problems emerged with daily dosing (elevation of liver aminotransferase). Abandoned at Phase III Clinical Trial.

Question 36

CGRP Antagonists Rimegepant (Nurtek) is one of the few remaining small molecule CGRP receptor antagonists that remains in clinical development • __ migraine treatment • less effect on __ levels (safer for longterm use)

Answer 36

Rimegepant (Nurtek) is one of the few remaining small molecule CGRP receptor antagonists that remains in clinical development • effective migraine treatment • less effect on liver aminotransferase levels (safer for longterm use)