 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).

Classification 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

StageDiagnosisTherapies Mild Occasional throbbing headache. No major functional impairment. Acetaminophen NSAIDS 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 agonists Prophylactic medications

1. Drugs for acute migraine or abortive treatment of migraine 2. Drugs for prophylactic treatment or prevention of migraine

Drugs for Aborting Migraine Headache :  5 HT-1 B / D receptors agonists : ERGOT ALKALOIDS  Dihydroergotamine  Ergotamine TRIPTANS  Sumatriptan  Rizatriptan  Naratriptan  Zolmitriptan

Drugs 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.

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.

Triptan 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.

Drugs 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

Adverse 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

PROPHYLACTIC 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

Drugs 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

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.

Drugs 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.

A 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

 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