Migraine is a severe headache accompanied by nausea, vomiting, light and sound sensitivity. It is caused by vasodilation of cranial blood vessels. Treatment includes acute medications like triptans and ergot alkaloids to constrict vessels and relieve symptoms. Prophylactic drugs like beta-blockers, antidepressants, and anticonvulsants are used to reduce migraine frequency. Triptans are the most effective acute treatment but can have cardiovascular side effects, while ergot alkaloids are less tolerated but more specific vasoconstrictors. Prophylaxis is recommended for those with frequent or severe migraines.

1. Antimigraine drugs
Dr. M. Ahsan, MBBS, MD

2. Learning Outcomes….
• Define migraine.
• Explain the biological basis of migraine & describe the types of
migraine.
• List the drugs used in the treatment of migraine.
• Explain the pharmacodynamics of different drugs used in the
treatment of migraine.
• Explain the pharmacokinetics of various drugs used in the treatment
of migraine.

3. Definition
• Migraine is a severe, unilateral, pulsating headache that typically lasts
from 2- 72 hrs
Headache is accompanied by nausea, vomiting, photophobia and
phonophobia
Headache is worsened by physical activity
Women are threefold more likely than men to experience migraine

4. Types of migraine
 Classical migraine
• Migraine with preceding neurological
symptoms called “aura”
• Aura can be visual, sensory, and/or
cause speech or motor disturbances
• Visual auras (flashes, zigzag lines,
glare) occur 20-40 mins before
headache begins
 Common migraine
• There is no preceding aura
• Majority of patients with migraine do
not have an aura

5. Severity of migraine
Mild
• Less than one
attack per
month
• Tolerable
headache
• Upto 8 hrs
Moderate
• More than one
attack per month
• More intense
throbbing headache
• Patient is
functionally
impaired
• Accompanied by
nausea and
vomiting
Severe
• 2-3 attacks per
month
• Severe throbbing
headache
accompanied with
vomiting
• Patient is severely
incapacitated
• Lasts for 12-48hrs

6. Biological basis of migraine
Depression of neuronal activity and reduced blood flow in the posterior
cerebral hemispheres causes “aura”
Hypoperfusion spreads forward over the surface of cortex
Followed by intracranial and extracranial arterial vasodilation
Release of inflammatory molecules (Substance P, neurokinin and CGRP)
Vasodilation stretches the duramater….which causes throbbing pain

7. Treatment of migraine
Drug therapy:
 Symptomatic treatment of
acute migraine
1. Non-specific drugs
2. Specific antimigraine drugs
 Prophylactic therapy
Non pharmacological
measures:
• Avoid triggers
• Meditation
• Yoga
• Relaxation therapy
• Psychotherapy

8. Drug therapy of acute migraine
Non specific drugs
• Analgesics
• NSAIDs
• Antiemetics
Specific antimigraine drugs
• Triptans
• Ergot alkaloids

9. Nonspecific drugs for acute migraine
• Paracetamol
• Aspirin
Analgesics
• Ibuprofen/Diclofenac
/Ketorolac/Naproxen
• They can be used in
combination with
caffeine/codeine/dia
zepam
NSAIDs
• Metoclopramide
• Domeperidone
• Diphenhydramine
• Promethazine
Antiemetics

10. Triptans
• Sumatriptan
• Naratriptan
• Rizatriptan
• Eletriptan
• Almotriptan
• Frovatriptan
• Zolmitriptan
• Sumatriptan
Given by oral/subcutaneous/
intranasal route
• Zolmitriptan
Given by oral route/ Nasal spray
All other triptans are given orally
Sumatriptan was the first available
triptan and is a prototype of the
class

11. Triptans
• Administered in the prodromal phase – it can rapidly terminate an
attack
• Better tolerated than ergot alkaloids
• Suppresses nausea (unlike ergot alkaloids)
• 70% patients respond to triptans
…relief from headache in 1-2 hrs when drug is taken orally
…when given parenterally, action begins in 20 mins
…Headaches recurs within 24 - 48 hrs after single dose

12. Mechanism of action of Triptans
• 5HT 1D/1B receptor agonists
The triptans have at least 3 distinct modes of action:
Vasoconstriction of painfully distended intracranial extra-cerebral
vessels
Inhibition of release of vasoactive neuropeptides by trigeminal
terminals innervating the intracranial vessels and dura mater.
 Inhibition of nociceptive neurotransmission within the
trigeminocervical complex in the brainstem and upper spinal cord.

13. Triptans
Side effects:
Significant elevation of blood pressure and cardiac events have been
reported with triptan use
Contraindicated in patients with risk factors for CAD
Should not be used with ergot alkaloids
Should not be used with MAO inhibitors
Other side effects:
• Pain and pressure sensation in chest, neck, throat, and jaw
• Dizziness and malaise

14. Ergot alkaloids
• Obtained from the fungus Ergot (Claviceps purpurea)
…..grows on rye, millet, other grains. The grain is replaced by hard
“Sclerotium”
• Ergot alkaloids used in migraine are:
Ergotamine
Dihydroergotamine

15. Ergot alkaloids
Given in prodromal phase – it can abort an attack
Ergotamine – given by oral/sublingual route
Partial agonist of 5-HT 1B/1D located on intracranial blood vessels
Also binds to α receptors and dopamine receptors
Constricts dilated cranial vessels (5- HT1 action)
Reduces neurogenic inflammation
1mg given orally every half hour till relief or upto maximum 6 mg

16. Ergotamine
• Vasoconstrictor
Therefore cannot be administered to patients with
coronary diseases
• In addition, ergotamine..
Inhibits release of calcitonin gene-related peptide
(CGRP) and other inflammatory mediators
Interact with many different neurotransmitter
receptors (α and dopamine) thus, not specific

17. Ergotamine
Novel drugs: CGRP-receptor antagonists
are being explored for treatment of
migraine
Ergotamine also inhibits
the release of
inflammatory mediators
like CGRP

18. Ergotamine
• Ergotamine has erratic oral absorption…..gastric stasis during
migraine reduces absorption
• Metoclopramide improves the absorption of ergotamine by reducing
gastric stasis
• The elimination of ergotamine is biphasic; half-lives of about 2 and 21
hours have been reported for the 2 phases, respectively

19. Dihydroergotamine
Semisynthetic derivative
Given parenterally (iv) or nasally
Used in severe cases of migraine or intractable migraine only

20. Ergotamine & Dihydroergotamine
• Side effects
Nausea and vomiting (give
antiemetics)
Can cause dull background headache
Dependence and rebound headaches
occur
• Contraindicated in :
Pregnancy……….can cause fetal
distress and miscarriages
Peripheral vascular disease and
CAD…...because they are significant
vasoconstrictors
…..Used only when triptans fail

21. Action of anti-migraine drugs

22. Prophylaxis of migraine
They are used if:
• Attack occurs two or more times a month
• Headaches are severe
• Headaches are complicated by serious neurological signs
Several classes of drugs are effective in reducing the frequency and
severity of migraine attacks.
Prophylactic therapy does not abort an attack !!!

23. Prophylaxis of migraine
• Drugs which can be used for prophylaxis of migraine:
β-blockers are the drug of choice….(Propranolol 40-160 mg BD)
Tricyclic antidepressants: Amitryptyline
Calcium channel blockers: Flunarizine, Verapamil
Anticonvulsants:
Valproic acid/Gabapentin/Topiramate