ACUTE MIGRAINE: OLD AND NEW DRUGS
Transcript of ACUTE MIGRAINE: OLD AND NEW DRUGS
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. .
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.
"MILD" MIGRAINE
- ASA
-APAP/ASA/CAFFEINE
-NSAID'S
-ADJUNCTIVE THERAPY (DARK ROOM/COLD COMPRESS)
-NATURAL'S
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
SPEED
- Injectable
-Nasal Spray
-Tablet
-Pharmokinetics
TOLERABILITY
-Triptan Effect
-Injection pain
-Taste
-MLT
COST
-Generic
-Brand Name
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.
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
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)