Migraine Drugs

Question 1

What are the 9 Abortive Drugs for Migraines?

serotonin 5 HT, Ergot, Dopamine, Analgesics

Answer 1

Specific serotonin 5-HT agonists
1) sumatriptan
2) zolmitriptan

Ergot Alkaloids
3) dihydroergotamine

Dopamine Antagonists
4) Metoclopramide
5) Prochlorperazine
6) Chlorpromazine

Analgesics
7) Aspirin
8) Acetaminophen
9) Ibuprofen

Question 2

Name 7 Prophylactic Drugs for Migraines

Answer 2

Beta-blockers
1) propranolol
2) metoprolol
3) timolol

Antidepressants
4) Amitriptyline

Anticonvulsant
5) Topiramate

6) Calcitonin gene-related peptide (CGRP) ligand or receptor antagonists - newer drugs

7) Botulinum toxin type A

Question 3

Explain oral absorption of drugs during migraines, what route is preferred and what therapeutic strategies to use.

Answer 3

Oral absorption of drugs is slowed during migraine:
 Deceased GI motility – caffeine helps to reduce this
 Nausea/vomiting (90%)

Parenteral routes of administration should be used

High variability with individual response to drug therapy, therapeutic strategies must be customized

Question 4

What are the 4 phases of a migraine?

Answer 4

1) Prodrome
2) Aura
3) Headache
4) Postdrome

Question 5

Characteristics of prodromes.

Answer 5

≤ 60%; changes in mood (depression, irritability,
etc…) & appetite (food cravings) that occur
hours to days before the migraine

Question 6

Characteristics or Aura Stage

with / without aura, incidence

Answer 6

Migraine without aura (Common Migraine)

Migraine with aura (Classic Migraine)

≤ 25 % of people with migraine

Question 7

Characteristics of headache phase of migraine?

pain, location, other symptoms, duration, symptom improvement

Answer 7

Progression from a dull ache to intense pulsations

Usually unilateral and occur in the frontotemporal
region and may extend to the neck and back of skull

Accompanied by nausea and vomiting (~90%)

Photophobia and Phonophobia

Migraine Lasts 4 -72 hours

Symptoms improve with resting in a dark room and
worsen with physical activity

More common in women versus men

Question 8

What frequency of migraines determines whether to use abortive therapy v. prophylactic therapy?

Answer 8

≤ 2 attacks per week;
Abortive therapy

≥ 3 attacks per week;
Prophylactic therapy

Question 9

What are rebound headaches, and what is associated with their occurance?

Answer 9

Rebound headaches are characterized by an increase in
headache frequency and an increase in drug consumption

Combination analgesics, opiates, ergotamine tartrate
and triptans are associated with rebound headaches

Question 10

What should be done to avoid rebound headaches? What is the only drug useful in relieving medication overuse headaches?

Answer 10

To avoid the problem of rebound headaches abortive
therapy should be used ~ 2 times a week

Only botulinum toxin is useful relieving medication
overuse headaches

Question 11

NSAIDs for Abortive Therapy: Efficacy, MOA and contraindications

Answer 11

Relative efficacy of the different NSAIDs for treating
migraine has not been clearly established

Mechanism of action: block prostaglandin synthesis and prevent inflammation in the trigeminovascular system

Use with caution in patients with peptic ulcer disease,
renal disease or hypersensitivity to aspirin.

Question 12

Describe usefulness in treating migraines with acetaminophen

Answer 12

Acetaminophen – efficacious in treating migraine pain and symptoms including photophobia and phonophobia

Question 13

Ergotamine route, t1/2 and dosage.

Answer 13

Route: Oral, sublingual and suppository

Dosage: The maximum oral/sublingual dose should not exceed 6 mg/attack or 10mg/week .

The biological half life of ergotamine is ~2 hrs, however ergotamine-induced vasoconstriction (duration of action) can last ~24 hrs

Question 14

Pharmacodynamics of Ergotamine: What receptors, how does it reduce neurogenic inflammation?

Answer 14

Ergotamine is a dirty drug and interacts with serotonin,
dopamine and adrenergic receptors.

Activation of 5-HT1B receptors causing vasoconstriction

Reduce neurogenic inflammation by decreasing the release of vasodilator/proinflammatory neuropeptide transmitters (e.g. substance P, neurokinin A, CGRP)

Question 15

Ergot Alkaloid contraindications, drug interactions and side effects

what adjunct therapy can help alleviate side-effects

Answer 15

Powerful vasoconstrictor –
 Partial agonist at alpha-adrenoceptors and 5-HT2
receptors, contraindicated in patients with peripheral
vascular disease and pregnancy (category X).

 Beta-blockers may potentiate vasoconstriction caused
by ergotamine. Patients on both medications should
be closely monitored

Side-effects: Nausea, vomiting and anorexia
Occurs in 10% of patients due to activation of central dopamine receptors
May require adjunct therapy with antiemetic (10mg Metoclopramide)

Question 16

Dihydroergotamine: Route, pharmacodynamics, toxicity and adverse reactions

Answer 16

Incompletely absorbed form the GI tract and is
administered parenterally (IM,SQ) or via a nasal
spray (Migranol)

Pharmacodynamics – similar to ergotamine

Toxicity, adverse reactions, and contraindications
similar to ergotamine except dihydroergotamine
causes vasospasm less than ergotamine

Question 17

Triptans: Route, metabolized by, contraindications.

How long after onset of migraine can the still be effective?

Answer 17

subcutaneous injection, oral tablets, nasal spray or transdermal patch

Metabolized by MAO-A, contraindicated with the use of a
MAO inhibitor within a 2 week time span after discontinuing
MAO therapy

Triptans can be administered up to 4 hrs after the onset of a
headache and still be effective

Question 18

Sumatriptan pharmacodynamics

receptor, symptoms treated

Answer 18

Sumatriptan is an agonist at type 1 serotonin receptors, similar action as the ergot alkaloids

Relieves nausea/vomiting and photophobia/phonophobia

Question 19

Triptans: Toxicity, adverse reactions and contraindications

what route should not be used to administer?

Answer 19

Cardiovascular (coronary spasm, myocardial infarction,
ventricular arrhythmias)

Several fatalities reported with subcutaneous sumatriptan
due to myocardial infarction

Do not give by IV due to due to the risk of vasospasm

Use of sumatriptan is contraindicated within 24 hrs of
treatment with an ergot due to the risk of additive vasospastic effects.

Question 20

Triptan side-effects

Answer 20

Common with sumatriptan and newer triptans:
chest and throat tightness, difficulty breathing, panic/anxiety,
paresthesia, feeling of heaviness

Question 21

2nd gen Triptans (zolmitriptan)

locations of action, other areas of action, oral absorption

Answer 21

Like sumatriptan these drugs act at the peripheral
components of the trigeminovascular system

Due to greater lipid solubility they also act centrally to
inhibit pain transmission in the trigeminal nucleus
(see Figure 1)

Better oral absorption versus sumatriptan (Imitrex

Question 22

Dopamine antagonists: Name 3 kinds, what they are useful for, route and what they do.

Answer 22

Metoclopramide
Prochlorperazine
Chlorpromazine

These dopamine antagonists are useful for the
treatment of acute migraine attacks that are
unresponsive to sumatriptan, DHE or oral analgesics

 Given by IV when administered in emergency
department

 Relieve headache pain and have anti-emetic activity

Question 23

Prophylactic Therapy: When to use them, how long until they are considered ineffective. What to do after 3-6 months for effective patient.

Answer 23

Consider prophylactic therapies with patients
who don’t respond to acute therapies or who
have ≥ 3 migraines per week.

Patients need to try these therapies for 2-3
months before they are considered ineffective.

If effective patient should stay on the drug for 3
- 6 months, after this time, try to remove the
drug to determine if remission has occurred.

Question 24

Which two B-blockers are FDA approved for migraine? What is one other that is also effective?

Answer 24

Propranolol and timolol are FDA approved for migraine

 Metoprolol is also effective

Question 25

Prophylactic Drug Therapy – β Blockers: MOA and what should be avoided

Answer 25

Mechanism of action is not clear but these drugs do have some affinity for serotonin receptors

 Beta-blockers with intrinsic sympathomimetic activity (partial agonist) e.g. acebutolol, pindolol, and penbutolol are not effective and should not be used for migraine therapy

Question 26

Amitriptyline: Type, MOA, side-effects

Answer 26

Antidepressant prophylactic drug

Mechanism of action of amitriptyline is unknown, independent of antidepressant action, may involve
down-regulation of central 5-HT2 and adrenergic
receptors

Sedation and anticholinergic side-effects (dry mouth,
blurred vision, urinary retention, cardiac arrhythmia)

Fluoxetine (Prozac) has fewer anticholinergic side
effects

Question 27

Topiramate: Type, MOA, side-effects

Answer 27

Type: Anti-seizure drug for Migraine treatment

MOA: – unknown for migraines, facilitate GABA neurotransmission, modulate glutamate, inhibit sodium and
calcium channels

Side-effects: paresthesia, fatique, anorexia/nausea, diarrhea,
weight loss, memory problems (cognitive slowness)

Question 28

Calcitonin gene-related peptide: Type, clinical trial effectiveness

Answer 28

Type: Prophylactic Drug Therapy

Drugs with – “mab” suffix are human monoclonal antibodies; rimegepant and atogepant are small-molecule drugs given PO
All have been approved since 2018
Clinical trials show modest but significant effects – no “magic bullets” here

Question 29

Botulinum Toxin A: MOA, route, length of action

Answer 29

Anti-migraine effect is not well understood

Injection of 70 – 100 units into a number of possible
sites (frontalis, glabellar, temporalis, masseter, splenius
capiti, paraspinal cervical, and trapezius muscles)

The anti-migraine effect can potentially last for up to 3
months and is only medication for rebound headaches