PHARMACOTHERAPY

OF
MIGRAIN

BY
JASTRIA PUSMARANI, S. FARM., M. SC., APT
WHAT IS A MIGRAINE?
 Nyeri yang terpusat pada salah satu bagian di kepala
 Lemahnya neuobiologi pada gangguan di kepala
 Prevalensi:
 18% women
 6% men
 Two categories
 80% common migraine
 20% classis migraine (with aura)
 Status migrainosus
CAUSES
 Mechanism still debated
 Common triggers
 Hormonal estrogen and progesterone
 Foods Alcohol, chocholate, etc
 Stress, physical activity, sleep
 Envieontmental stimulus sight, smells
 Medications
4 PHASES OF A MIGRAINE

Prodrome

Aura

Headache

Postdrome
 PRODROME
• Stage of Migraine that is characterized by:
• difficulty concentrating,
• yawning,
• fatigue and/or sensitivity to light and noise.
• Duration: A few hours to a few days
 AURA
• Stage of migraine that is characterized by :
• visual illusions of sparks and lights,
• often followed by blind or
• dark spots in the same place as the bright
hallucinations
• Duration: 20-60 minutes
 HEADACHE
• Stage characterized by
excruciating or throbbing pain
along with sensitivity to light
and sound.
• May be accompanied by
nausea and vomiting
• Sometimes only half of the
head or part of the head is in
pain.
• Duration: 4 – 72 hours
POSTDROME
• Characterized by:
• sensitivity to light and
movement
• Lethargy
• Fatigue
• Difficulty focusing
• Also called a “zombie phase”
• Duration: A few hours to a few
days
THE 4 PHASES OF A MIGRAINE
 TRIGGERS
 Stress Foods containing
 Emotion • MSG
 Glare • tyramine
 Hypoglycemia • nitrates
• phenylethylamine
 Altered Sleep Pattern
• aspartame
 Menses
Drugs
 Exercise
• Estrogen (eg. OC)
 Alcohol • Nitroglycerin
 Excess caffeine • Excess analgesic use or
/withdrawal withdrawal
 PATHOPHYSIOLOGY:
TRIGGERS
TRIGERS

Emotional Physical Chemical

Locus Cerelus
Sympathetic system Dorsal Raphe

Release of NA Release of 5-HT

Stimulation of 5 HT 2B
Vasocontriction or 5HT 7

Vasocontriction
 RESPONSE TO
VASOCONSTRICTION
Vasoconstriction

stimulation of PNS Peripheral

release of NO Trigeminal
from neurons afferents

vasodilation effect thalamus Trigeminal

Nucleus c

HA HA Spinal CGRP Hypothalmus

Trigeminal

Cervical Muscle vasodilation cervical inflammation Photophobia

causing Phonophobia
head & neck pain

Headche Headache
WAYS TO TREAT MIGRAINES
• Avoiding Trigger Factors
• Simple Non-Drug Treatment
• Pain Medications
• Prophylactic Medications
“Abortive Medications”
(acute, specific medications)
• Magnesium
SIMPLE NON-DRUG TREATMENTS
Massages
Ice to head

Heat to head
TREATMENT STRATEGIES & GOALS
Acute Treatment
• decrease duration of attack
Prophylaxis
• decrease severity, duration and frequency
• Based on severity & frequency of migraine attacks
NON-PHARMACOLOGICAL METHODS
Effective > 50%
• Diet, education re: triggers,relaxation
Moderately effective 30-50%
• Stop smoking, exercise, riboflavin
Ineffective <30%
• Avoiding tyramine, aspartame,chocolate
• Magnesium, feverfew
 PAIN MEDICATIONS
• Aspirin
• Acetaminophen
• NSAIDS- Non steroidal anti-inflammatory drugs.
 “ABORTIVE MEDICATIONS”
Triptans Ergots
• Current Triptans in use: • Current ergots in use
• Sumatriptan • DHE
• Naratriptan • Ergotamine
• Zolmitriptan Tartrate
• Rizatriptan. • Cafergot
• Almotriptan • Isomethaheptane
• Frovatriptan
• Eletriptan
PHARMACOLOGIC TREATMENT
OF ACUTE MIGRAINE
• Pretreatment with an antiemetic
• eg, metoclopramide, chlorpromazine, or prochlorperazine
• 15 to 30 minutes before oral or nonoral migraine
treatments
(rectal suppositories, nasal spray, or injections
• In addition to its antiemetic effects, metoclopramide
helps reverse gastroparesis and enhances absorption of
oral medications.
• This occurs commonly with over use of simple or combination
analgesics, opiates, ergotamine tartrate, and triptans.
• Limit use of acute migraine therapies to 2 or 3 days per
week.
ANALGESICS AND NONSTEROIDAL
ANTIINFLAMMATORY DRUGS
• Simple analgesics and nonsteroidal anti-inflammatory drugs
(NSAIDs) are firstline treatments for mild to moderate migraine
attacks; some severe attacks are also responsive.
• Aspirin, diclofenac, ibuprofen, ketorolac, naproxen sodium,
tolfenamic acid, and the combination of acetaminophen plus
aspirin and caffeine are effective.
• NSAIDs appear to prevent neurogenically mediated
inflammation in the trigeminovascular system by inhibiting
prostaglandin synthesis.
• The combination of acetaminophen, aspirin, and caffeine is
approved in the United States for relieving migraine pain.
ERGOTAMINE
 Structurally similar to amines,
serotonin, norepinephrine, and
dopamine
 interact with multiple receptors
in these systems
 cause constriction of the blood
vessels
 wide-range of effects
 Problems: avoid if patient has coronary disease; safety
margin is small; overdose
 ERGOT ALKALOIDS
AND DERIVATIVES
• They are nonselective 5HT1 receptor agonists that constrict
intracranial blood vessels and inhibit
the development of neurogenic inflammation in the
trigeminovascular system.
• Venous and arterial constriction occurs.
• They also have activity at dopaminergic receptors.
• Ergotamine tartrate is available for oral, sublingual, and
rectal administration.
• Oral and rectal preparations contain caffeine to enhance
absorption and potentiate analgesia.
• Titrate to an effective dose that is not nauseating.
NEXT...
• Dihydroergotamine (DHE) is available for
intranasal and parenteral (IM, IV, or subcutaneous
[SC]) administration.
• Patients can self-administer IM or SC DHE
• Nausea and vomiting are common with ergotamine
derivatives, so consider antiemetic pretreatment.
• Other common side effects include abdominal pain,
weakness, fatigue, paresthesias, muscle pain, diarrhea,
and chest tightness.
• Do not use ergotamine derivatives and triptans
within 24 hours of each other.
• Contraindications to use of ergot derivatives include
renal and hepatic failure; coronary, cerebral, or
peripheral vascular disease; uncontrolled
hypertension; sepsis; and women who are pregnant or
nursing.
SEROTONIN RECEPTOR
AGONISTS (TRIPTANS)
• The triptans are appropriate first-line therapies for
patients with mild to severe migraine or as rescue
therapy when nonspecific medications are ineffective.
• They are selective agonists of the 5HT1B and 5HT1D
receptors.
• Relief of migraine headache results from (1)
1. normalization of dilated intracranial arteries,
2. inhibition of vasoactive peptide release, and
3. inhibition of transmission through second order
neurons ascending to the thalamus.
• Sumatriptan SC injection is packaged as an autoinjector
device for self-administration.
• Intranasal sumatriptan also has a faster onset of effect than
the oral formulation and produces similar rates of response.
• Second-generation triptans (all except sumatriptan) have
higher oral bioavailabilityand longer half-lives than oral
sumatriptan, which could theoretically reduce headache
recurrence. However, comparative clinical trials are
necessary to determine their relative efficacy.
• Side effects of triptans include paresthesias, fatigue,
dizziness, flushing, warm sensations, and somnolence
OPIOIDS
• Reserve opioids and derivatives (eg, meperidine,
butorphanol, oxycodone, and hydromorphone) for
patients with moderate to severe infrequent
headaches in whom conventional therapies are
contraindicated or as rescue medication after failure
to respond to conventional therapies. Closely supervise
opioid therapy.