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 PREVALENCE36 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 HISTORYTHE 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 INFLAMMATIONVASODILATION

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 MGMAGNESIUM OXIDE 75 MG

DICLOFENAC 50 MG

DISPOSABLECOLD COMPRESS

CAPSAICINNASAL 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

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

COMINGSOON?

SUMATRIPTAN/NAPROXEN (U.S.)

SUMATRIPTAN TRANSDERMALIONTOPHORETICPATCH

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

AIR INJECTEDSUMATRIPTAN

LEVADEX(R) : INHALED DHE POWDER

WHAT'SNEW?

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