Migraine headaches presentation[1].ppt pharmacology

Pharmacology

1. Vishal Sharma

2. Overview
Migraine and Statistics
History
Classification and symptoms
Etiology and Pathophysiology
Treatment

3. 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.

4. 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.

5. History cont.
In 2
nd
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
17
th
century
In 80s, Dr. Harold G. Wolff said that
dilation of blood vessels is the main cause
of migraine.

6. 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.

7. Negative scotoma. Loss of local awareness of local structure

Positive Scotoma. Additional structures One side loss of perception.
Zigzag structure

8. 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.

9. 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.

10. Etiology and
Pathophysiology
The precise etiology and
pathophysiology of migraine is
unknown.
However, neuronal dysfunction theory
is most acknowledged theory.
Activity in trigeminovascular system.

12. Abnormal
Neuronal activity
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
Activates nociceptive
trigeminovascular
system and causes
prolong pain
Cerebral cortex, thalamus or
hypothalamus in response to
stress, emotion.
‡

13. Abnormal
Neuronal activity
Releases vasoactive
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 prolong
headache
Activates
trigeminovascular
system, which in turn,
stimulate pain
stimulating neurons in
brain stem and upper
spinal cord
Activates nociceptive
trigeminovascular
system and causes
prolong pain
Cerebral cortex, thalamus or
hypothalamus in response to
stress, emotion.
‡
Bos
s

14. 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.

15. 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

16. 5- HT
1
Presynaptic receptor
5- HT
2
Postsynaptic receptor
Serotonin binds to
5-HT
1
and 5-HT
2

17. 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

18. 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

19. 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.

20. 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

21. 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.

22. Prophylactic therapy
cont.
Calcium channel Blockers-
Verapmil
Takes up to 8 weeks to show any good
effect
Side effects- Hypotension, constipation
etc

23. 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.

24. 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.

25. Corticosteroids mediate glucose metabolism and inflammation
Arachidoni
c
Acid (AA)
Plasma Membrane
phospholipids
Phospholipase A2
Prostaglandins,
leukotrienes
Cyclooxygena
se
(COX)
AspirinAnnexin
Inflammation,
Asthma
Non-steroidal
Anti-inflammatory
Steroidal (corticosteroid)
Anti-inflammatory

26. Abortive therapy cont.
3) Ergot family
Ergotamine-
It 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

28. Abortive therapy
5) Triptan Family
5-HT1 receptor agonists
Examples-
Sumatriptan – Imitrex
Zolmitriptan – Zomig
Rizatriptan – Maxalt
Eletriptan – Relpax
Naratriptan - Amerge

29. Elitriptan
Sumatriptan
Rizatriptan Zolmitriptan

30. Side Effects
 nausea, vomiting, dizziness, fatigue,
and vertigo.
Not good for hypertensive patients at
all.

31. 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.

32. 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.

33. 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. 

34. 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?