1. Caroline is a 30-year-old woman who presents with increasing migraine frequency over the past few months, with some migraines causing her to miss work. 2. Previous treatments for both acute migraine attacks and migraine prevention have been ineffective or caused side effects, including weight gain, dizziness, and depression. 3. Her current medications - naratriptan for acute attacks, valproic acid and sertraline for prevention - are also providing minimal relief or efficacy. Evaluation of alternative treatment options is needed given treatment failure of previous pharmacological approaches.

1. CLINICAL STUDY
OF
MIGRAINE
Presented by:
Syed Dastagir Hussain
M.Pharmacy 1st year
CMR COLLEGE OF PHARMACY

2. GENERAL CLASSIFICATION OF HEADAHE:
Although various schemes preceded it, the 1988 classification of the International Headache
Society (IHS)7 was the first to be widely adopted. In 2003 International Classification of
Headache Disorders, 2nd edition (ICHD-II). Major three types of headache according to
severity
 Primary headache:
Migraine , Tension-type headache , Cluster headache and chronic
paroxysmal hemicrania
 Secondary headache:
trauma, Subarachnoid haemorrhage , non-vascular intracranial disorders, substances or
their Withdrawal,non-cephalic infection, or facial pain associated with disorder of
cranium, neck, eyes,ears, nose, sinuses, teeth, mouth or other facial or cranial
 Neuralgias and other headaches:
Cranial neuralgia and facial pain

3. INTRODUCTION:
Migraine is primary type of headache it shows unilateral episodes with or without GIT,
photophobic and sons phobic symptoms it is further classified into two major sub types
 Migraine with aura
 Migraine without aura
Migraine with aura :
Two or more headache attacks that comply with three of the following characteristics:
(e) One or more fully reversible aura symptoms indicating cerebral cortical or brainstem
dysfunction.
(f) At least one aura symptom developing over more than 4 min, or two or more symptoms
occurring in succession.
(g) No aura symptom should last for more than 1 h.
(h) Headache follows aura with a pain-free interval of less than 1 h.

4. Migraine without aura :
Repeated headache attacks, lasting for 4–72 h, with the following features:
recurrent moderate to severe, throbbing headache, usually unilateral but sometimes bilateral,
accompanied by intolerance of light or noise, nausea, and sometimes vomiting.
The pain should comply with at least two of:
(a) Normal physical examination.
(b) No other reasonable cause for the headache.
(c) At least two of:
• Unilateral pain.
• Throbbing pain.
• Aggravation of pain with head movement.
• Moderate to severe intensity of pain.
(d) At least one of:
• Nausea or vomiting.
• Photophobia and sonophobia.

6. EPIDEMIOLOGY
• Migraine is common worldwide, reported variously as affecting 5–25% of
women and 2–20% of men.
• Migraine without aura is at 10–11 years of age in males and 14–17 years in females.
• That of migraine with aura is at about 5 years in males and about 12–13 years in females.
• There is then a slow increase in prevalence in women up to age 40 years,
but the prevalence of all forms declines after the age of 45–50.
• Some 10% of the population are ‘active migraineurs’.
• 5% have 18 or more migraine days annually; 1% have one each day or week.
• The average duration of an attack is about 24 h, but may be 2–3 days in 20% of patients.

7. AETIOLOGY:
• Alterations in cerebral blood flow is probably incorrect
• Vascular changes reflect cranial disturbance
• Vasodilatation of cranial or meningeal blood vessels, or oedema
• Due to a small clot, because the circle can be supplied by any of its ascending arteries,
• The cerebral veins have no valves, have very thin walls, and no muscle layer ,
• Reflecting systolic heartbeats, blood from the brain and skull.
• Genetical mutation.

8. Precipitating Factors Associated with Migraine

10. PATHOLOGY:
• Migraineurs probably have a genetically determined, or congenital, reduced
CNS excitation threshold, However, mutations have been identified in genes for
the voltage-gated calcium and sodium channels and for the alpha2 subunit of
the Na/K pump in some types of familial migraine.
• Thus the concept that vascular changes may account for the prodrome , and
that the subsequent headache is caused by vasodilatation is no longer tenable.
• Dilatation of the carotid arterial circulation causes stretching of arterial walls
and so thickening of the meninges, producing pain.
• Serotonin (5-HT), released by vascular nerves or platelets, is clearly implicated
in the pathogenesis of migraine.
• Nitric oxide is also implicated in CNS vasodilatation

12. DIAGNOSIS:
 IHS diagnostic criteria for migraine without aura
a. At least 5 attacks fulfilling criteria b-d
b. Headache attacks lasting 4-72 hours(untreated or unsuccessfully treated)
c. Headache has at least two of the following characteristics:
1. unilateral location
2. pulsating quality (ie, varying with the heartbeat)
3. moderate or severe pain intensity
4. aggravation by or causing avoidance of routine physical activity
(eg, walking or climbing stairs)
d. During headache at least one of the following:
1. nausea and/or vomiting
2. photophobia and phonophobia
e. Not attributed to another disorder:
(history and examination do not suggest a secondary headache disorder or, if they
do, it is ruled out by appropriate investigations or headache attacks do not occur for the fi rst
time in close temporal relation to the other disorder)

13. Migraine with aura diagnosis:
Diagnosed relatively easily. The occurence of aura preceding episodic headache clinches it ,
but beware of patients who bring "visual disturbance" into their accounts because of what
they have read about migraine. Visual blurring and "spots" are not diagnostic.
Transient hemianopic disturbances prior to headache, lasting 10-30 minutes (occasionally
up to 1 hour) other reversible focal neurological disturbances such as unilateral paraesthesiae
of hand, arm or face (the leg is rarely affected),
are symptoms of migraine aura.
Investigation of headache patients
Investigations, including cranial CT, do not contribute to the diagnosis of migraine or of TTH.
They are indicated only when history or examination suggest headache may be
secondary to some other condition. Cervical spine x-rays are indicated when neck signs
suggest origin from the neck, although they may not reveal a treatable condition.

14. MANAGEMENT:
OBJECTIVES:
. Cure is not a realistic aim and patients need to understand this
.The shared objective should be control of symptoms so that the effect of the illness on a
patient’s life and lifestyle is the least it can be.
Types of Management:
1. Pharmacological management
2. Non Pharmacological management
a. Physical therapy:
acupuncture, dental treatment
b. Psychological therapy:
relaxation therapy, stress reduction and coping strategies
biofeedback techniques
hypnotherapy
c. Herbals and homoeopathy
d. Other alternative remedies:
Reflexology

15. 1. Pharmacological management:
Steps and classes of
drug
Drug and dose/day Dosage
form
contraindications
Step one :
a. Simple oral
analgesics
(or)
b. Simple oral
analgesics
aspirin 900mg or
paracetamol 1000mg or
ibuprofen 400mg
tolfenamic acid 200mg
naproxen 500mg
diclofenac 50-75mg
Anti-emitics:
metoclopramide 10mg or
domperidone 20mg
Combination:
1.paracetamol 500mg
+metoclopramide 5mg /10mg
2.Acetylsalicylate
1620mg+aspirin
900mg+metoclopramide 10mg
3.Paracetamol
500mg+domperidone10mg
tab
tab
tab
tab
tab
tab
tab
tab
Sachet/
tab
Sachet
tab
Aspirin seen in child
it should avoid with
Metoclopramide and
adoescents.
In adults there are
none, unless it has
clearly failed before

16. Steps and classes of
drug
Drug and dose/day Dosage form Contraindications
and adverse drug
effect
Step two :
Simple parenteral
analgesics
Diclofenac 100mg +
domperidone 30mg
Suppositories
Peptic ulcer to over
come daily give
misoprostol 800µ g or
omeprazole 20-40 mg
Step three :
Specific anti-migraine
drugs :
1. triptans Sumatriptan 100mg
Sumatriptan 20mg
Sumatriptan 6mg
Zolmitriptan 2.5mg
Rizatriptan 10mg
Naratriptan 2.5mg
orally
nasal spray
S.C
tab
S.C
tab
Uncontrolled
hypertension, In case
of uncertainty,
cardiological referral
and exercise ECG are
recommended.
Children under 12
years:
no experience has
been reported and
neither safety nor
efficacy are
established.

17. Steps and classes of
drug
Drug and dose/day Dosage form Contraindications
and adverse drug
effect
Step four : Dihydroergotamine 1mg
ergotamine 1-2mg
Nasal spray
suppository
beta-blockers, not
advised for children,
cases of digital
gangrene have been
reported
Step five : steps one + three
+diclofenac 75mg-inj
(or)
steps two + three
+diclofenac 75mg-inj
3ml from MI
Emergency treatment of patients :
i. intramuscular diclofenac 75mg
ii. intramuscular chlorpromazine 25-50mg

18. Patients who consistently experience recurrence :
There is some evidence that this occurs more in those whose untreated attacks last
longer than 24 hours.
• Naratriptan
• Ergotamine
Long-duration migraine:
Migraine lasting longer than 3 days is uncommon
• naproxen or diclofenac
Slowly developing migraine:
• simple analgesics
• Triptans should not be used
Migraine in pregnancy and lactation:
• Paracetamol in moderation is safe
• Aspirin is safe except near to term
• For nausea, prochlorperazine is unlikely to cause harm throughout pregnancy and lactation
• Metoclopramide and domperidone are probably safe in second and third trimesters.

19. Drugs to avoid in acute intervention:
• Opiates or opiate derivatives (morphine,pethidine,dextroproxyphene,codeine,
dihydrocodeine) These drugs increase nausea, promote systemic shut-down and have
addictive potential
Limits to acute therapy: frequency of use
• Use on more than two days per week is clearly inappropriate for migraine (though not
necessarily unsafe).
• Use on more than one day per week calls for close enquiry into how it is used, and review
of the diagnosis.

21. prophylactic therapy: is used in addition to, not instead of, acute therapy. The
evidence-base for all prophylactic anti-migraine drugs is poor except
Duration of use:
4-6 months
3-4 weeks minimum

22. First-line prophylactic drugs :
• Beta-adrenergic blockers without partial agonism
• Sodium valproate 0.6-2.5mg
• Pizotifen 1.5mg daily
• Amitriptyline 10-150mg daily
• Desipramine, nortriptyline and protriptyline
Second-line prophylactic drugs :
• Methysergide 1-2mg tds
• Beta-blocker and amitriptyline

23. Steps followed by there clinical features which classes of drug to be choice and
accordenting to there severity

24. CASE STUDY
Name: Caroline parker age : 30.yr sex: female
Wt.kg: 70 BP:132/86Hg HR:76
Chief Complaint :
This new medication is not working for my headaches, and I have been gaining weight
Present illness:
30-year-old woman who presents to the Neurology Clinic for follow-up of migraine
headaches. Since then, the frequency of her migraines has increased to about four to
five per month. Vomiting may occur with an extreme headache. She reports
experiencing severe migraine attacks that cause her to miss 2 days of work each
month. Migraine with aura since age 27
previous medical :
1. Simple analgesics, NSAIDs, and Cafergot (good efficacy until 2 months ago)
2. Narcotics (good efficacy, but puts her “out of commission for days”)
3. Midrin (no efficacy) 4. Naratriptan (minimal efficacy)

25. • Prophylactic therapies
1. Valproic acid 500 mg daily (weight gain) 2. Propranolol 20 mg BID (increased episodes
of dizziness and lightheadedness; patient self-discontinued medication) • Mild depression
for 8 months, treated with
1. Phenelzine 15 mg po TID (minimal efficacy, discontinued 1 month ago) 2. Sertraline 50
mg po at bedtime (recently started 2 weeks ago)
Present midecatin:
Naratriptan 2.5-mg tablets, 1 tablet po at onset of migraine, repeat dose of 2.5 mg po
in 4 hours if partial response or if headache returns. Maximum dose 5 mg per 24 hours.
Metoclopramide 10 mg po at onset of migraine. Valproic acid 500 mg po at bedtime.
Sertraline 50 mg po at bedtime.
Conclusion:
1. Increase in frequency of migraines related to an increase in stress.
2. Minimal efficacy of naratriptan 2.5 mg po as an abortive treatment.
3. Previous prophylactic treatments have been unsuccessful and cause unwanted
adverse effects

26. Thank you