Migraine (MC) - Block 2

Question 1

What factors affect treatment?

Answer 1

Onset: infection or nasal
DOA: Shorter DOA – might have recurrence of migraine
Presence of N/V: Nasal sprays/injectables

Question 2

What is the difference between rescue and prophylactic?

Answer 2

Rescue: relieves existing attack
Prophylactic: prevent an attack from occurring

Question 3

MOA of triptans?

Answer 3

Activate 5-HT1D/1B receptors on presynaptic trigeminal nerve endings -> inhibit release of vasodilating peptides

Question 4

What is the function of 5-HT1D/1B receptors?

Answer 4

Mediate vasoconstriction

Question 5

What is the function of 5-HT1F?

Answer 5

Inhibits trigeminal nerve activation

Question 6

Describe the SAR of triptans?

Answer 6

Question 7

Why was sumatriptan unable to penetrate the BBB?

Answer 7

Too hydrophilic

Question 8

When is it best to take a triptan?

Answer 8

As soon as a patient gets a migraine attack

Question 9

ADR of triptans?

Answer 9

1. Altered sensations
2. Chest discomfort (CI: CAD and angina)

ADR more severe with short half-life and faster acting

Question 10

Triptan tablets?

Answer 10

Good absorption, slower onset, potential gastric stasis

Question 11

ODT triptans?

Answer 11

Good absorption, may not work in all aptients, taste disturbances

Question 12

Nasal spray triptans?

Answer 12

15 minue onset, tast disturbances

Question 13

SC Triptans?

Answer 13

Sumatriptan only: very rapid absorption, inj site rx, expensive

Question 14

Major interactions for triptans?

Answer 14

Major concern is serotonin syndrome
MOAI, SSRI, SNRI, ergots

Question 15

Where is the site of action for seratonic agonists?

Answer 15

Selective 5-HT1F receptor agonist: blocks trigeminal nerve activation/inflammation
* Lacks VC action of triptans -> better CV safety than triptans

Question 16

Types of seratonin? ADR?

Answer 16

Lasmiditan
ADR: DZ, N, parasthesias, drowsiness

Question 17

MOA for ergots?

Answer 17

Partial agonist at a-adrenoreceptor and partial agonist at 5HT2 receptors
* Vasoconstrictor
* Specific for migraine pain

Question 18

Why does ergots have poor bioavailability? How is it improved?

Answer 18

Peptide; given with caffiene to aid absorption if given PO

Question 19

ADR of ergots?

Answer 19

GI (D/N/V)
Greater degree of peripehral vasoconstriction (avoid in coronary disease)

Question 20

What drug should not be given to patient with coronary disease?

Answer 20

Ergots

Question 21

Examples of DA for N and Pain?

Answer 21

Prochlorperazine (IV/IM)
Chlorpromazine (IV/IM)
Metoclopramide (IV)

Question 22

Receptor activity of DA?

Answer 22

D2 receptors:
1. Central effect on dopaminergic neurons for migraine
2. Work at chemoreceptor trigger zone to improve nausea
3. Improves GI motility to increase medication absorption

Question 23

Function of CGRP receptor antagonist?

Answer 23

Block vasodilatory and trigeminal nerve sensitization effects of CGRP

Question 24

Examples of CGRP receptor antagonists?

Answer 24

Ubrogepant
Rimegepant
Atogepant

Question 25

Ubrogepant | ADR

Answer 25

N, fatigue, dry mouth

Question 26

Rimegepant | ADR

Answer 26

N, UTI

Question 27

What is the purpose for prophylaxise?

Answer 27

1. Reduces frequency, severity and duration of attacks 1. Prevent evolution of episodic headaches to chronic daily headaches 1. Improve responsiveness to treatment of acute attacks 1. May take 8 – 12 weeks to be effective

Question 28

Prophylaxis for migraines

Answer 28

1. Propanalol/timolol 2. Topiramate 3. Amitriptyline 4. Botox Other agents: 1. Divalproex/Valproic acid 2. Frovatriptan (MAM) 3. Venlafaxine 4. Calcium channel blockers (verapamil) - off labe (Prevents blood vessel changes in migraine and cluster headache) 5. NSAIDs (mild acute attacks and MAMs)

Question 29

MOA of propanalol/timolol

Answer 29

1. Vasoconstriction 2. Anxiolytic action 3. Decrease sympathetic activity

Question 30

Topiramate MOA?

Answer 30

Cognitive side effects/tingling sensation in figers and toes may limit use * Weight loss + mood stabilizer

Question 31

Amitriptylline | MOA, ADR

Answer 31

**MOA:** Blocks reuptake of norepinephrine and/or serotonin * Useful when migraines co-exist with tension-type headache, chronic pain conditions, disturbed sleep or depression **ADR:** dry mouth, sedation, DZ, N

Question 32

Botox | MOA

Answer 32

**MOA:** Inhibtis release of ACh at NMJ -> inhibits striated muscle contractions * pain relief often occurs before muscle paralysis * Blocks peripheral nerve sensitization * Blocks release of glutamate and SubP from nociceptive neurons

Question 33

CGRP Monoclonal Antibody Antagonists MOA?

Answer 33

Antagonize either CGRP peptide or its receptor

Question 34

TYpes of CGRP Monoclonal Antibody Antagonists?

Answer 34

Erenumab binds to CGRP receptor Fremanezumab/galcanezumab/eptinezumab bind to CGRP + prevent binding to and activation of receptor

Question 35

CGRP Monoclonal Antibody Antagonists | ADR, Use

Answer 35

**ADR:** inj site rx or erythema **Use:** effective, good safety/tolerability, expensive and SC