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

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

2 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

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

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

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7 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

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9 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..

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

11 ASPIRIN/CAFFEINE

12 NEUROTIC - TENSE - OVERWHELMED

13 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.

14 BARBITURATE AND NARCOTIC (AVOID/RESCUE)

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16 MIGRAINE PATHOPHYSIOLOGY

17 "ALLERGIES MEETS GOUT"

18 PAIN INFLAMMATION VASODILATION

19 ICSI.ORG (MSP, MN)

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21 INFLAMMATORY "MESS"

22 RECOGNIZE THE LEVEL OF SEVERITY AND DISABILITY. TREAT ACCORDINGLY

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

24 ASA 500 MG MAGNESIUM OXIDE 75 MG

25 DICLOFENAC 50 MG

26 DISPOSABLE COLD COMPRESS

27 CAPSAICIN NASAL SPRAY

28 ESSENTIAL OILS: PEPPERMINT/LAVENDER

29 "MODERATE" MIGRAINE

30 TRIPTANS (SNIPER)

31 TRIPTANS SEARCH FOR A NEW ANTI-MIGRAINE DRUG STARTED AT GLAXO IN 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

32 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.

33 TRIPTANS

34 SUMATRIPTAN FORMULATIONS

35 SUMATRIPTAN

36 TRIPTANS

37 TRIPTANS

38 TRIPTANS

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

40 ERGOTAMINES

41 ERGOTAMINE ("SHOTGUN") THE MOLECULE WAS FIRST ISOLATED FROM THE ERGOT FUNGUS BY ARTHUR STOLL AT SANDOZ IN 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.

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

43 DIHYDROERGOTAMINE 45 NASAL SPRAY

44 ADVERSE EFFECTS

45 D.H.E.45 INJECTABLE

46 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

47 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

48 COMING SOON?

49 SUMATRIPTAN/NAPROXEN (U.S.)

50 SUMATRIPTAN TRANSDERMAL IONTOPHORETIC PATCH

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

52 AIR INJECTED SUMATRIPTAN

53 LEVADEX(R) : INHALED DHE POWDER

54 WHAT'S NEW?

55 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 , EXPECTED TO BE EXPENSIVE($10,000/MONTH)

56 CGRP MONOCLONAL ANTIBODY ANTAGONIST

57 CONCLUSION

58 WHEN LIGHTNING STRIKES "ACUTE MIGRAINE"

59 ACT QUICKLY!!!

60 SUPPLEMENT AS NEEDED!!!

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

62 PREVENT MIGRAINE TRANSFORMATION!!!

63 THANK YOU