migraine headaches
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Vishal Sharma. Migraine headaches. Overview. Migraine and Statistics History Classification and symptoms Etiology and Pathophysiology Treatment. Migraine and statistics. - PowerPoint PPT PresentationTRANSCRIPT
Vishal Sharma
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 migraineDoes not give any warning signs before the onset
of headache.It occurs in about 70 to 80% of migraine patients2) Migraine with AuraGive 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.
Negative scotoma. Loss of local awareness of local structure
Positive Scotoma. Additional structures One side loss of perception.
Zigzag structure
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
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.
‡
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.
‡
Boss
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 causesVasodilation Serotonin causesVasoconstrictionDuring migraine the level of serotonin is
low in blood. (Low Ph)Drug target
5- HT1 Presynaptic receptor
5- HT2 Postsynaptic receptor
Serotonin binds to 5-HT1 and 5-HT2
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 therapy2)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 antidepressantsFor example, amitryptiline, nortryptiline,
doxepin, imipramine etcIndependent 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 mealsSide 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 acetaminophenAspirin+acetaminophen+barbiturate
butabital = To induce sleepaspirin+acetaminophen+narcotics =
FiorinalAspirin+ acetaminophen+caffiene =
EsgicDrawback- 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
Arachidonic Acid (AA)
Plasma Membranephospholipids
Phospholipase A2
Prostaglandins,leukotrienes
Cyclooxygenase(COX)
AspirinAnnexin
Inflammation,Asthma
Non-steroidalAnti-inflammatory
Steroidal (corticosteroid)Anti-inflammatory
Abortive therapy cont.
3) Ergot familyErgotamine- It is secondary metabolite obtained from
ergot fungusDihydroergotamine- 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
ElitriptanSumatriptan
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?