Vishal Sharma
MIGRAINE HEADACHES
Overview
 Migraine and Statistics
 History
 Classification and symptoms
 Etiology and Pathophysiology
 Treatment
Migraine and statistics
 Migraine is a neurovascular disease caused by
neurogenic inflammation and characterized
by severe, recurring headaches
 It usually characterized by the severe pain on
one side of the head as compare to the pain
in rest of the head.
 It occurs more often in Women than in men.
History
 History goes back to 9000 years.
 First mode of treatment: trepanation
 Medical intervention in which a hole is drilled or scraped into the
human skull, exposing the dura mater in order to treat health
problems related to intracranial diseases.
History cont.
 In 2nd century AD, Pergamum a Greek physician used a
term hemicrania.
 The brain and stomach were connected
 “Migraine” evolved from this term
 However, this idea was replaced by blood flow in 17th
century
 In 80s, Dr. Harold G. Wolff said that dilation of
blood vessels is the main cause of migraine.
Classification of Migraine
headache.
1) Migraine without Aura or common migraine
Does not give any warning signs before the onset of
headache.
It occurs in about 70 to 80% of migraine patients
2) Migraine with Aura
Give some warning signs “ called aura” before the
actual headache begins. Approximate, 20 to 30%
migraine sufferers experience aura.
The most common aura is visual and may include both
positive and negative (visual field defects) features.
Zigzag structure
Negative scotoma. Loss of local awareness of local structure
Positive Scotoma. Additional structures
One side loss of perception.
Classification of Migraine
headache cont.
3) Retinal migraine
It involves attacks of monocular scotoma or even
blindness of one eye for less than an hour and
associated with headache.
4) Childhood periodic syndromes that involve
cyclical vomiting (occasional intense periods of
vomiting), abdominal migraine (abdominal pain,
usually accompanied by nausea), and benign
paroxysmal vertigo of childhood (occasional
attacks of vertigo).
They may be precursors or associated with
migraine.
Classification of Migraine
headache cont.
 5) Complications of migraine describe
migraine headaches and/or auras that are
unusually long or unusually frequent, or
associated with a seizure or brain lesion.
Etiology and Pathophysiology
 The precise etiology and pathophysiology of
migraine is unknown.
 However, neuronal dysfunction theory is
most acknowledged theory.
 Activity in trigeminovascular system.
Abnormal
Neuronal activity
Cerebral cortex, thalamus or
hypothalamus in response to
stress, emotion.
‡
Activates nociceptive
trigeminovascular
system and causes
prolong pain
Instability in release of
neuropeptides e.g.,
Substance P, neurokinin A,
calcitonin gene-related
polypeptide, serotonin
Promote
vasodilation and
plasma protein
extravasations.
Initiate
inflammatory
response,
sensitizes
surrounding
tissues and
produce headache
Activates
trigeminovascular
system, which in turn,
stimulate pain
stimulating neurons in
brain stem and upper
spinal cord
Abnormal
Neuronal activity
Cerebral cortex, thalamus or
hypothalamus in response to
stress, emotion.
‡
Releases vasoactive
neuropeptides e.g.,
Substance P, neurokinin A,
calcitonin gene-related
polypeptide, serotonin
Promote
vasodilation and
plasma protein
extravasations.
Boss
Initiate
inflammatory
response,
sensitizes
surrounding
tissues and
produce prolong
headache
Activates nociceptive
trigeminovascular
system and causes
prolong pain
Activates
trigeminovascular
system, which in turn,
stimulate pain
stimulating neurons in
brain stem and upper
spinal cord
Serotonin
 Neurotransmittor
 Serotonin ( 5- hydroxytryptamine) is thought
to be an important mediator of migraine.
 Unstable serotonergic neurotransmission , so
has lower threshold for migraine.
 There are 7 classes of 5-HT receptors
 Out of 7, 2 involve in migraine pain.
Serotonin cont.
 It is basic as amines and Ammonia
 Changes Ph of blood
 Serotonin causes
Vasodilation
 Serotonin causes
Vasoconstriction
During migraine the level of serotonin is low in
blood. (Low Ph)
Drug target
5- HT1 Presynaptic receptor
Serotonin binds to
5-HT1 and 5-HT2
5- HT2 Postsynaptic receptor
How bad could migraine be…
 It could distrub the normal life activities.
 Could lead to brain damage
 Recently, a woman in London had a migraine
 Lost her accent
Treatment
 Identification and elimination of factors.
For example, Tobacco smoke, loud noise, stress,
caffeine, emotions, contrasty light etc.
If they don’t work then move on to medicines
1) Prophylactic therapy
2) Abortive therapy
Prophylactic therapy
 Used in case of frequent migraines
 Used when abortive therapy has failed
 Medicines have to taken everyday to be
effective
 On the other hand, abortive medicine are
taken during actual migraine pain.
Medicines used in this therapy
 1) Medicines that block beta-adrenergic.
For example, Propranolol, nadodol, timolol,
atenolol, and metoprolol.
Reduce the frequency of attacks by 50% in 60 to
80% patients.
Side effects- fatugue, sleep disturbance,
depression, hypotension etc
Cont.
 2) Tricyclic antidepressants
For example, amitryptiline, nortryptiline, doxepin,
imipramine etc
Independent of antidepressant activity.
Antagonist of 5-HT2, thus stabelize serotonin
neurotransmission
 3) Methysergide:Semisynthetic ergot alkaloid and is 5-HT2 antagonist.
Gives best result when taken with meals
Side effects- gastrointestinal intolerence, insomnia, and muscle
cramps.
Prophylactic therapy cont.
 Calcium channel Blockers Verapmil
 Takes up to 8 weeks to show any good effect
 Side effects- Hypotension, constipation etc
Abortive therapy
 1) simple analgesics:-
For mild and infrequent migraine- Aspirin and
acetaminophen
Aspirin+acetaminophen+barbiturate butabital =
To induce sleep
aspirin+acetaminophen+narcotics = Fiorinal
Aspirin+ acetaminophen+caffiene = Esgic
Drawback- Continuous use fails to provide pain
relief.
Abortive Therapy cont.
 2) NSAIDs: Inhibit prostaglandin synthesis.
 So may prevent inflammation in
trigeminovascular system and alleviate
migraine pain
 They are effective for reducing the frequency,
severity, and duration of migraine attacks.
e,g. Aspirin, Ibuprofen, Naproxen etc.
Corticosteroids mediate glucose metabolism and inflammation
Inflammation,
Asthma
Plasma Membrane
phospholipids
Arachidonic
Acid (AA)
Annexin
Prostaglandins,
leukotrienes
Aspirin
Phospholipase A2
Steroidal (corticosteroid)
Anti-inflammatory
Cyclooxygenase
(COX)
Non-steroidal
Anti-inflammatory
Abortive therapy cont.
 3) Ergot family
ErgotamineIt is secondary metabolite obtained from ergot
fungus
Dihydroergotamine- available in inject able form.
The structure shares some similarit with
neurotransmittor serotonin.
Acts as agonist, bind to 5-HT1,
More effective when given during early migraine attacks
Abortive therapy
 5) Triptan Family
 5-HT1 receptor agonists
 Examples-
Sumatriptan – Imitrex
Zolmitriptan – Zomig
Rizatriptan – Maxalt
Eletriptan – Relpax
Naratriptan - Amerge
Elitriptan
Sumatriptan
Rizatriptan
Zolmitriptan
Side Effects
 nausea, vomiting, dizziness, fatigue, and
vertigo.
 Not good for hypertensive patients at all.
Ergot and Triptan comparison
 The rates of ergotamine and sumatriptan
overuse were 14.2% and 3.5%, respectively
 Drug-induced headache could be found more
frequently in cases of ergotamine overuse
then drugs of triptan family.
Miscellaneous agent
 Midrin = Isometheptane+
dichlorophenazene+ acetaminophen
 Used in patients who do not respond to ergot
and triptan
 Less effective then ergot and triptan family’s
drugs
 Most frequent side effects are nausea,
dizziness, insomnia, and vomiting.
References
 "Etymology of migraine". Online Etymological Dictionary.
http://www.etymonline.com/index.php?term=migraine. Retrieved
27 May 2009
 http://en.wikipedia.org/wiki/Migraine
 Headache Classification Subcommittee of the International
Headache Society (2004). "The International Classification of
Headache Disorders: 2nd edition". Cephalalgia 24 Suppl 1: 9–160.
doi:10.1111/j.1468-2982.2004.00653.x. PMID 14979299.
Questions
 Name the major neurotransmitter that
mediate the migraine pain.
 Name major medicines that act as 5-HT1
agonist and 5-HT antagonist.
 How does NSAIDs work?