Definition, types and Classification of Migraine according to severity - Pathophysiology of Migraine (Vascular & Neurovascular) - Drug Therapy of Acute Migraine attack & Prophylaxis according to SIGN & NICE guidelines - Triptans & Ergots mechanism of action, side effects and drug interactions - Management of Migraine in Woman (Menstrual, Hormonal contraception, Pregnancy)

1. Drug Therapy of Migraine
Prof. Sawsan Aboul-Fotouh
Department of pharmacology, faculty of Medicine, Ain shams University

2. What is Migraine?
• Episodic headache, typically unilateral, associated
with vomiting and visual disturbance.
• Four phases
American Migraine Foundation, 2018

3. Acute Migraine Attack
American Migraine Foundation, 2018
(Classic migraine)

4. American Migraine Foundation, 2018

5. American Migraine Foundation, 2018

6. Two main types of migraine
Migraine without aura
(Common migraine).
Migraine with aura
(Classic migraine)

7. Classification of Migraine according
to severity

8. Pathophysiology of Migraine
I. “Vascular Theory” II. “Neurovascular Theory ”

9. Pathophysiology of Migraine
I. “Vascular Theory”
Cerebral Vasospasm → Cerebral
ischemia → transient neurologic
symptoms (Aura).
Compensatory Vasodilation
of Intracranial & extracranial
vasculature → (Headache)
On the 1940s and 1950s

10. Pathophysiology of Migraine
II. “Neurovascular Theory ”
5 Steps

11. 1. Wave of Neuronal Excitation=
Cortical Spreading Depression
(CSD) begin in occipital Lobe
2. Release VC e.g. NE, 5-HT
→ oligemia→ Aura Visual
3. CSD → +++ TN nucleus & nerve
Trigeminovascular system
4. Release Neuroinflammatory
peptides e.g. PG, NO, Calcitonin
Generated Peptide (CGRP), SP,
VIP → Dural VD & + Nociceptors
→ Throbbing Headache
“Migraine center”
& Nucleus
5. Stimulation of LC, DRN, PAG,
Thalamus, cortex , Area postrema
(→ vomiting), Hypothalamus
(hypersensitivity Photophobia &
Phonophobia), cervical Trigeminal
system (ms spasm) → Migraine.
Central
sensitization
Peripheral
sensitization
Dural
VD

12. Management of migraine
(with or without aura)
NICE guidelines, 2020

13. I. Mild analgesics: NSAIDs & Aspirin, Acetaminophen
(for mild infrequent attacks).
II. Triptans: 1st line antimigraine therapy: for outpatients (moderate - severe )
III. Ergots: 5HT 1B/1D agonists similar to triptans (NOT 1st line)
IV. Antiemetics
• Parenteral metoclopramide (monotherapy in emergency; if ineffective add IV
dihydroergotamine).
• Oral metoclopramide → added to other antimigraine drugs (ergotamine) to
increase their absorption by its prokinetic effect.
• Domperidone can be used
V. Benzodiazepines & opioids in resistant cases
(may lead to habituation & rebound headache)
Drugs Therapy of acute migraine attack
+ Caffeine ??

14. Mechanism of action (selective 5HT1B/1D agonists)
1. Activate 5HT1B/1D receptors on presynaptic trigeminal nerve →inhibit release of VD neuropeptides.
2. VC of dural vessels → prevent stretching of pain nerve endings.
Preparations of triptans : Sumatriptan: prototype (oral, SC, nasal spray)
Triptans are more effective in early migraine attack or when the headache is still mild.
Triptans

15. Adverse effects:
1. Injection site reaction (with SC) or unpleasant taste (with intranasal).
2. Chest pressure (resolves spontaneously in 30 minutes).
3. Paresthesia, warmth, drowsiness, dizziness, weakness, malaise.
Contraindications & Precautions:
1. Uncontrolled hypertension, ischemic stroke & IHD →
2. 1st dose given cautiously in diabetics, hypertensives, men >40 & in postmenopausals.
3. Pregnancy (cautiously).
4. Drug interaction: with 5-HT drugs: SSRIs, MAOI or within 24 hrs of ergots (→ 5HT syndrome).
Triptans

16. Mech: 5HT 1B/1D agonists similar to triptans (Partial) + α1 agonist
1. Ergotamine tartrate (+Caffeine →↑absorption &↑ C. VC)
(sublingual, oral, rectal); of choice in prolonged or frequent headaches.
2. Dihydroergotamine (IV, IM, SC & intranasal).
Adverse effects & contraindications :
1. GIT: Nausea, vomiting, diarrhea.
2. Chest pressure.
3. Prolonged Vasospasm→ gangrene (CI peripheral vascular disease), Angina.
4. CI. Pregnancy (++ Ut. Contraction, VS).
5. Should not be used for long term (Fibrosis→ valvular heart disease, Pulm..).
Ergots
ERGOTISM
Ergots
α1

17. Drug Interaction: ergotamine or Cafergot with potent CYP3A4 inhibitors e.g.
protease inhibitors or macrolide antibiotics → serious adverse events cerebral
ischemia and/or ischemia of the extremities ; for this reason, these drugs
should not be given concomitantly with ergotamine.
COVID-19
COVID-19

18. Anti-migraine therapy should NOT exceed 10 -15
days / month to avoid Medication Overuse
Headache “MOH”.
Ergotamines have more side effects than triptans
and analgesics →They should therefore NO
longer be used as the therapy of first choice.

19. Drugs Therapy of acute migraine attack
SIGN guidelines, 2018

20. 1. Beta blockers: Propranolol and Timolol: are of choice in hypertension ..
2. Antidepressants: Amitriptyline (esp. in depression..) SSRI …
3. Anticonvulsants: Valproate & Topiramate. (↓ Excess firing of TN). Esp. in epilepsy…
4. CCBs: Verapamil (→ tolerance), Flunarizine .
5. CGRP Receptor antagonist : Erenumab (FDA, 2018) 70mg S.C. once/month for chronic migraine (>15d/month)
6. Triptans: frovatriptan1 (2.5mg twice/d) or zolmitriptan2 (2.5 mg 2-3 times/d) in Menstrual Migraine.
Drugs for migraine prophylaxis
Others: 5HT2 antagonists e.g. Cyproheptadine, pizotifen, mirtazapine, ACEI, ARBs candesartan Mg, V B2,
Clonidine, Onabotulinum toxin A (FDA,2010) for chronic migraine
(> 2 attacks/Month)

21. FDA, 2018

22. SIGN guidelines, 2018
Drugs Therapy of Migraine Prophylaxis

23. Menstrual-related migraine
If does not respond to standard acute treatment, consider frovatriptan1 (2.5 mg twice a day) or
zolmitriptan2 (2.5 mg twice or three times a day) on the days migraine is expected (for Prophylaxis).
Combined hormonal contraceptive use
Avoid combined hormonal contraceptives in migraine with aura (↑ risk of Ischemic stroke).
Migraine during pregnancy or Lactation
-For acute migraine: Paracetamol 1st choice, may use triptan or NSAID cautiously ??!!.
-For prophylactic: low dose Propranolol, Amitriptyline, Aspirin (75mg/day)
NICE guidelines, 2020
1st & 2nd trimesters
1st trimester
sumatriptan

24. Other options for migraine headache:
• Vagus Nerve Stimulation:
- by acupuncture
• Spring TMS
– Transcranial magnetic stimulation
• Skull cap :Cefaly
– Tens-like unit