Migraine Headaches--Treatment and Prevention

Question 1

Migraine–neural events provoke

Answer 1

-dilation of cranial blood vessels

Question 2

Goal of therapeutic agents

Answer 2

-rescue patient from start of a migraine

Question 3

Medication taken in prodrome phase

Answer 3

• Triptans–5HT1B/1D Receptor agonists

- Ergot alkaloids

Question 4

Medications taken in headache phase

Answer 4

• NSAIDS

- Acetaminophen

Question 5

Preventative agents

Answer 5

-B blockers
-Tricyclic antidepressants
-anticonvulsants
-Ca channels
(given in asymptomatic phase)

Question 6

neurogenic inflammation theory of migraine

Answer 6

-wave of electrical cavity
-stimulates release of neuropeptides (CGRP, substance P) and inflammatory mediators
(NO, histamine, prostaglandins)
-dilate cranial blood vessels and sensitive nerves to pain

Question 7

step 1

Answer 7

• brainstem dysfunction sparks a wave of excitation/depression in Cortex–H, K, NO discharge from neurons
• cerebral vasoconstriction

Question 8

step 2

Answer 8

• electrolytes and NO diffuse and dilate cranial arteries and depolarize perivascular trigeminal terminals
• CGRP and neuropeptides promote neurogenic inflammation

Question 9

step 3

Answer 9

neurogenic inflammation irritates TG n and transmits migraine pain

Question 10

2 key mediators–interact throughout trigeminal neuromuscular system

Answer 10

-CGRP and NO

Question 11

used to treat coronary a disease

Answer 11

• Organic nitrates (NO)

- Can provoke migraine

Question 12

cranial vessels–R

Answer 12

5HT-1B

Question 13

peripheral neuron R

Answer 13

5HT-1 D

Question 14

central neuron R

Answer 14

-5HT 1B/iD

Question 15

serotonin receptor-vascular and synaptic

Answer 15

• vascular-5HT1B R

- synaptic-5HT 1 D R

Question 16

Triptans mechanism

Answer 16

• selective 5HT1D/1B receptor agonist
• 5HT-1B Receptor stimulates vasoconstriction
• 5HT-1D Receptor inhibits pre-synaptic release of CGRP

Question 17

Triptan prototype

Answer 17

Sumatriptan

Question 18

Sumatriptan–p.o.

Answer 18

• Cmax=1-2 hours
• 15% bioavailability–unreliable in some patients
• clearance-t/12=1-2 hours

Question 19

Sumatriptan-other delivery options

Answer 19

• SC-Cmax=15 minutes

- nasal spray=30 minutes

Question 20

Sumatriptan-metabolized by

Answer 20

MAO-A

Question 21

Other triptans

Answer 21

• Almotriptan
• Naratriptan-70% bioavailability; t/12 is 6 hours
• Zolmitriptan–active metabolite
• Rizatriptan
• Eletriptan
• Frovatriptan–t1/2=24 hours

Question 22

choice of delivery route

Answer 22

• oral-easy to take, ineffective if patient vomits
• nasal spray–effective with vomiting, simple, works quickly; few triptans formulated as nasal sprays
• injection–works quickly; inconvenient

Question 23

Sumatriptan–delivery options

Answer 23

• injectable subcutaneous
• nasal spray
• tablets

Question 24

Zolmmitriptan-delivery options

Answer 24

• tablets
• orally disintegrating tablets
• nasal spray

Question 25

Quick onset--what delivery options

Answer 25

- nasal spray--fast | - subcutaneous--sumatriptan fastest

Question 26

is patient taking other medications? consider?

Answer 26

- serotonin syndrome | - MAO interactions

Question 27

Triptans--contraindications

Answer 27

- ischemic/vasospastic coronary disease - cardiovascular disorder - uncontrolled hypertension

Question 28

contraindicated in patients taking MAO inhibitors

Answer 28

-Sumatriptran -rizatriptan -zolmitriptan (metabolized by MAO)

Question 29

used for severe or refractory migraine

Answer 29

-ergot alkaloids

Question 30

Ergot alkaloids

Answer 30

- Dihydroergotamine - Ergotamine and caffeine * less specific!!

Question 31

NEVER use what together??

Answer 31

triptan and DHE

Question 32

Ergot alkaloids--side effects

Answer 32

- strong emetic action | - vasoconstriction--St. Anthony's fire

Question 33

migraine treatment in pregnancy

Answer 33

- acetaminophen and codeine - aspirin-1 and 2nd trimester only - ibuprofen--1st and 2nd trimester only - triptans-cautiously

Question 34

migraine treatment in pregnancy--contraindicated

Answer 34

- DIhydroergotamine | - Other ergot alkaloids

Question 35

Botox and migraines?

Answer 35

- inhibits ACh release at motor endplates--reduce m activity | - not approved for migraines unless migraine isn't received from other meds

Question 36

preventive agents--taken daily, asymptomatic

Answer 36

- B blockers - Tricyclic antidepressants - Anticonvulsants - Ca channel blockers

Question 37

B blockers mechanism

Answer 37

- propranolol, timolol - anxiolytic action - decrease sympathetic activity - blunts cortical spreading depression * effective in 60-80%

Question 38

B blockers--cautions

Answer 38

- Normal well tolerated | - bronchoconstriction--contraindicated in asthma patients

Question 39

Tricyclic antidepressants

Answer 39

-amitriptylene, imipramine

Question 40

anticonvulsants

Answer 40

-topiramine, valproate

Question 41

Ca channel blockers

Answer 41

verapramil

Question 42

considerations for preventative therapy

Answer 42

- >2 migraines per month with disability - disability lasting >3 days per month - adverse effects from acute treatments - rescue medication used >2x per week - uncommon migraine conditions

Question 43

Ca channel blockers for migraine prevention--mechanism

Answer 43

- Verapamil - Lessens Ca dependent vesicle fusion - normalizes vessel tone