ACUTE MIGRAINE: OLD AND NEW DRUGS JOHN ROBROCK MD FORT WILLIAM FAMILY HEALTH TEAM

Conflict of Interest Declaration: Nothing to Disclose Presenter: John Robrock, MD Title of Presentation: Acute Migraine: New and Old Drugs I have no financial or personal relationships to disclose

OBJECTIVES 1. REVIEW ACUTE MIGRAINE PATHOPHYSIOLOGY 2. REVIEW CURRENT TREATMENT FOR ACUTE EPISODIC MIGRAINE 3. UPDATE ON NEW TREATMENTS FOR ACUTE EPISODIC MIGRAINE

MIGRAINE PREVALENCE 36 MILLION AMERICAN SUFFERERS APPROXIMATELY 1 : 4 INDIVIDUALS FEMALE > MALE PEAKS IN THE 40'S GENETIC CONDITION

COST TO SOCIETY ABSENTEEISM - LOST WAGES PRESENTISM - LOST PRODUCTION ENJOYMENT OF LIFE'S ACTIVITIES OVERALL COST BURDEN > MOST OTHER CHRONIC CONDITIONS INCLUDING ASTHMA, DIABETES AND DEPRESSION

MIGRAINE HISTORY THE HISTORY OF THIS CONDITION DATES BACK SUPPOSEDLY TO WHEN NEOLITHIC "SURGEONS" WOULD DRILL HOLES IN THE SKULLS OF HEADACHE SUFFERERS. HIPPOCRATES PRESCRIBED HERBS FOR HIS PATIENTS, AND GALEN LABELED WHAT MAY HAVE BEEN MIGRAINES OR MIGRAINE-LIKE HEADACHES "HEMICRANIA" BECAUSE OF THEIR TENDENCY TO OCCUR ON ONE SIDE OF THE HEAD AT A TIME. WILLIS, A BRITISH PHYSICIAN, USED THE WORD "MIGRUM" INSTEAD. ORIGINALLY IT WAS THOUGHT TO BE A PSYCHOLOGICAL DISORDER, AND SUFFERERS WOULD BE TREATED LIKE HYPOCHONDRIACS. THEY WERE THOUGHT TO BE NEUROTIC, OBSESSIVE, COMPULSIVE, RIGID, AND SUFFER FROM REPRESSED HOSTILITY..

WHAT'S OLD? "TAKE TWO ASPIRIN AND CALL ME IN THE MORNING"

ASPIRIN/CAFFEINE

NEUROTIC - TENSE - OVERWHELMED

FIORINAL - BUTALBITAL DR. ARNOLD FRIEDMAN, FOUNDER OF THE FIRST HOSPITAL BASED HEADACHE CLINIC AT MONTEFIORE MEDICAL CENTER IN THE BRONX, NEW YORK IN THE MID 1940'S, WORKING WITH SANDOZ PHARMACEUTICALS INVENTED AN ASPIRIN/CAFFEINE/BARBITURATE MEDICATION TO TREAT ACUTE HEADACHES.

BARBITURATE AND NARCOTIC (AVOID/RESCUE)

MIGRAINE PATHOPHYSIOLOGY

"ALLERGIES MEETS GOUT"

PAIN INFLAMMATION VASODILATION

ICSI.ORG (MSP, MN)

INFLAMMATORY "MESS"

RECOGNIZE THE LEVEL OF SEVERITY AND DISABILITY. TREAT ACCORDINGLY

"MILD" MIGRAINE - ASA -APAP/ASA/CAFFEINE -NSAID'S -ADJUNCTIVE THERAPY (DARK ROOM/COLD COMPRESS) -NATURAL'S

ASA 500 MG MAGNESIUM OXIDE 75 MG

DICLOFENAC 50 MG

DISPOSABLE COLD COMPRESS

CAPSAICIN NASAL SPRAY

ESSENTIAL OILS: PEPPERMINT/LAVENDER

"MODERATE" MIGRAINE

TRIPTANS (SNIPER)

TRIPTANS SEARCH FOR A NEW ANTI-MIGRAINE DRUG STARTED AT GLAXO IN 1972. RESEARCH LED TO THE DISCOVERY OF THE FIRST TRIPTAN DRUG, SUMATRIPTAN, THAT HAD BOTH VASOCONSTRICTION EFFECT, AS WELL AS BETTER ORAL BIOAVAILABILITY. SUMATRIPTAN WAS FIRST LAUNCHED IN THE NETHERLANDS IN 1991 AND BECAME AVAILABLE IN THE USA DURING 1993

TRIPTANS THEIR ACTION IS ATTRIBUTED TO THEIR AGONIST EFFECTS ON SEROTONIN 5-HT1B AND 5-HT1D RECEPTORS IN CRANIAL BLOOD VESSELS (CAUSING THEIR CONSTRICTION) AND SUBSEQUENT INHIBITION OF PRO-INFLAMMATORY NEUROPEPTIDE RELEASE. EVIDENCE IS ACCUMULATING THAT THESE DRUGS ARE EFFECTIVE BECAUSE THEY ACT ON SEROTONIN RECEPTORS IN NERVE ENDINGS AS WELL AS THE BLOOD VESSELS. THIS LEADS TO A DECREASE IN THE RELEASE OF SEVERAL PEPTIDES, INCLUDING CGRP AND SUBSTANCE P.

TRIPTANS

SUMATRIPTAN FORMULATIONS

SUMATRIPTAN

TRIPTANS

TRIPTANS SPEED - Injectable -Nasal Spray -Tablet -Pharmokinetics TOLERABILITY -Triptan Effect -Injection pain -Taste -MLT COST -Generic -Brand Name

ERGOTAMINES

ERGOTAMINE ("SHOTGUN") THE MOLECULE WAS FIRST ISOLATED FROM THE ERGOT FUNGUS BY ARTHUR STOLL AT SANDOZ IN 1918. THE MECHANISM OF ACTION OF ERGOTAMINE IS COMPLEX. THE MOLECULE SHARES STRUCTURAL SIMILARITY WITH NEUROTRANSMITTERS SUCH AS SEROTONIN, DOPAMINE, AND EPINEPHRINE AND CAN THUS BIND TO SEVERAL RECEPTORS ACTING AS AN AGONIST. THE ANTI-MIGRAINE EFFECT IS DUE TO CONSTRICTION OF THE INTRACRANIAL EXTRACEREBRAL BLOOD VESSELS THROUGH THE 5-HT1B RECEPTOR, AND BY INHIBITING TRIGEMINAL NEUROTRANSMISSION BY 5-HT1D RECEPTORS. ERGOTAMINE ALSO HAS EFFECTS ON THE DOPAMINE AND NOREPINEPHRINE RECEPTORS. ITS SIDE EFFECTS ARE DUE MAINLY TO ITS ACTION AT THE D2 DOPAMINE AND 5-HT1A RECEPTORS.

FORMS OF ERGOTS TABLETS (CAFERGOT, ERGOMAR) NASAL SPRAY (MIGRANAL) INJECTABLE (DHE 45)

DIHYDROERGOTAMINE 45 NASAL SPRAY

ADVERSE EFFECTS

D.H.E.45 INJECTABLE

D.H.E.45 CONTRAINDICATIONS PREGNANCY AND BREASTFEEDING HISTORY OF ISCHEMIC HEART DISEASE HISTORY OF PRINZMETAL'S ANGINA SEVERE PERIPHERAL VASCULAR DISEASE ONSET OF CHEST PAIN FOLLOWING ADMINISTRATION OF TEST DOSE WITHIN 24 HOURS OF RECEIVING ANY TRIPTAN OR ERGOT DERIVATIVE ELEVATED BLOOD PRESSURE PATIENTS WITH HEMIPLEGIC OR BASILAR-TYPE MIGRAINE * CEREBROVASCULAR DISEASE

TREAT ACCORDING TO THE SEVERITY OF PAIN AND THE LEVEL OF DISABILITY (REVIEW) MILD MIGRAINE o APAP/ASA/Caffeine o ASA alone o NSAIDs o Triptans MODERATE MIGRAINE o DHE (dihydroergotamine mesylate) o NSAIDs o Triptans SEVERE MIGRAINE o Prochlorperazine o Chlorpromazine o DHE o Ketorolac IM o Magnesium Sulfate IV o Triptans

COMING SOON?

SUMATRIPTAN/NAPROXEN (U.S.)

SUMATRIPTAN TRANSDERMAL IONTOPHORETIC PATCH

SUMATRIPTAN LOW DOSE (22 MG) DRY POWDER FORMULATION EFFECTIVE AS 100 MG ORAL, LESS ADVERSE EFFECTS

AIR INJECTED SUMATRIPTAN

LEVADEX(R) : INHALED DHE POWDER

WHAT'S NEW?

CGRP INHIBITOR A CALCITONIN GENE-RELATED PEPTIDE (CGRP) MONOCLONAL ANTI- BODY ANTAGONIST, A ONCE MONTHLY INJECTABLE "BIOLOGIC" ENTERING PHASE III STAGE OF TESTING. SO FAR IT HAS SHOWN TO BE VERY EFFECTIVE IN TREATING BOTH EPISODIC AS WELL AS CHRONIC MIGRAINE SUFFERERS. NOT READY FOR RELEASE UNTIL 2017-2018, EXPECTED TO BE EXPENSIVE($10,000/MONTH)

CGRP MONOCLONAL ANTIBODY ANTAGONIST

CONCLUSION

WHEN LIGHTNING STRIKES "ACUTE MIGRAINE"

ACT QUICKLY!!!

SUPPLEMENT AS NEEDED!!!

USE APPROPRIATE DOSAGES!!! USE APPROPRIATE FORMULATIONS!!!

PREVENT MIGRAINE TRANSFORMATION!!!

THANK YOU