Migraine Migraine is a benign and recurring

syndrome of headache, nausea and vomiting, and /or other neurological dysfunction.

Migraine, the most common cause of headache, afflicts approximately 15% women and 6% men.

Migraine can often be recognized by its activators (wine, menses, hunger, lack of sleep, worry, estrogens and glare) and deactivators (sleep and pregnancy).

MigraineClassification of Migraine headache Migraine without aura (common

migraine) • Pure menstrual migraine

Migraine with aura (classic migraine)• Familial hemiplegic migraine

Pathophysiology of Migraine : The vascular theory The neuronal theory

Migraine

Stage Diagnosis Therapies

Mild

Occasional throbbing headache. No major functional impairment.

AcetaminophenNSAIDS

Moderate

Moderate headache, Nausea common. Some impairment of functioning.

Oral, nasal or SC 5-HT-1 agonist

Severe

Severe headache > 3 times per month. Significant functional impairment. Marked nausea and /or vomiting

SC, IM or IV 5-HT agonistsProphylactic medications

Migraine1. Drugs for acute migraine or abortive treatment of migraine

2. Drugs for prophylactic treatment or prevention of migraine

Migraine

MigraineDrugs for Aborting Migraine

Headache : 5 HT-1 B / D receptors agonists :ERGOT ALKALOIDS Dihydroergotamine ErgotamineTRIPTANS Sumatriptan Rizatriptan Naratriptan Zolmitriptan

MigraineDrugs for Acute Migraine : Abortive drugs – Block the vasodilatation

or relieve pain and inflammation. 5- HT 1 B / D receptors are predominantly

presynaptic autoreceptors – activation by agonists inhibits release of serotonin and other neurotransmitters like Substance P and CGRP.

Also postsynaptically 5 HT 1 B / D agonists mediate vasoconstriction in cerebral blood vessels.

Migraine

Triptan drugs: 5-HT-1 agonists: These are very effective acute anti-

migraine agents but are not intended for use in prophylaxis.

Their ability to decrease nausea/vomiting is an important advance in the treatment of migraine.

Do not use triptans concurrently with or within 24 hours of ergot or other triptans.

MigraineTriptan drugs: Adverse effects : Coronary vasospasm especially in

patients with ischemic heart disease. There is the potential for life-threatening

serotonin syndrome in patients taking triptans and SSRIs or SNRIs at the same time.

Triptans are not recommended in patients taking MAOI or within two weeks of stopping one.

MigraineDrugs for Aborting Migraine Headache : ERGOT ALKALOIDS : Ergotamine / Dihydroergotamine Ergotamine (Ergomar): Most effective when given early in the migraine

attack for moderate and severe migraine. Ergotamine is available in sublingual, oral and

rectal formulations.Dihydroergotamine (Migranal): DHE available as intranasal and s.c, i.m, and i.v It is a weaker vasoconstrictor than ergotamine

MigraineAdverse effects : ERGOT ALKALOIDS Nausea and vomiting very common with

ergotamine but can be prevented by pretreatment with antiemetic prochlorperazine or metoclopramide.

Concomitant use of potent CYP 3A4 inhibitors avoided. (e.g., protease inhibitors and macrolide antibiotics)

Do not use in patients with ischemic heart disease or peripheral arterial disease.

Women who are or may become pregnant• Risk of fetal distress and miscarriage

MigrainePROPHYLACTIC THERAPY IN CHRONIC

MIGRAINE: Use in patients who

• Have > 3 significant attacks per month• Have > 2 days of headache-related

disability per month• Are poorly responsive to or can not use

acute abortive treatment• Have very frequent headache of any

intensity

MigraineDrugs for Preventing Migraine Headache

: Beta-adrenergic receptors blockers Anti-convulsants and Anti-depressants Calcium channel blockers Onabotulinumtoxin A for prophylaxis of

headache in adult patients with chronic migraine (>15 headache day/month for >3 months)

5-HT 2 receptors antagonists – Methylsergide

Migraine - Prophylaxis

Serotonin 5 – HT 2 receptors antagonists :

Methylsergide : Reserved for refractory migraine prophylaxis

Associated with risk of life threatening retroperitoneal, cardiac and pleural fibrosis and other safe drugs are preferred as prophylactic drugs for migraine.

It should not be used for more than 6 months continuously.

MigraineDrugs for Preventing Migraine Headache : Beta-adrenergic receptors blockers:

Propranolol and timolol are FDA approved but others are also effective in prevention.

Anti-convulsants: Valproate and topiramate are FDA approved for migraine prophylaxis. Patients taking any of these are at increased risk of suicidal ideation or behavior.

Calcium channel blockers: Verapamil is used in prophylaxis.

Anti-depressants (amitriptyline) is effective for prophylaxis in clinical trials.

Migraine

QuestionsA 33-year-old woman complained to her

physician of tingling and numbness in her fingers and toes. The woman had taken a high dose of a drug to abort a headache. Which of the following drugs was the most likely cause of her symptoms?

A) Ibuprofen B) Morphine C) Ergotamine D) Propranolol E) Duloxetine

Questions A 59-yr-old female patient with undiagnosed

coronary artery disease is given medication. Shortly thereafter she develops tightness and “crushing discomfort” of her chest. Her EKG reveals ST-segment changes indicative of acute myocardial ischemia. Which of the following drugs MOST LIKELY precipitated this event?• Benztropine for Parkinsonism.• Sumatriptan to abort a migraine attack• Morphine for post-operative analgesia• Phenytoin for generalized seizures• Sertraline for depression