UNIVERSITI TEKNOLOGI MARA PULAU PINANG

KAMPUS BERTAM
FACULTY OF PHARMACY

MIGRAINE

and what you should know

AUTHORS

Im always
getting
headaches.
Is it
migraine?

Mohd Redza bin Mohd Hanif

Muhamad Illias bin Mohamad
Ahmad Khairul Azwar bin Sukeri
Fatin Nur Nazihah binti Zainuddin
Hazatul Syifaa binti Mahamad Esha

TABLE OF CONTENTS

1.

Migraine The Introduction

2.

Pathophysiology of Migraine

3.

Risk Factors of Migraine

4.

Clinical Features of Migraine

45

5.

Pharmacotherapy Drugs

6 26

6.

Disease Management

27

7.

References

28

MIGRAINE THE INTRODUCTION

WHAT IS A MIGRAINE ?
Migraine is a type of headache characterized
by periodic attacks of pain, nausea, and
increased sensitivity to light and sound. The
pain is often worse on one side of the head,
throbbing or pulsating in nature, moderate
or severe in intensity, and disruptive of usual
activities of daily living.
Typically the headache affects one half of the
head, and pulsating in nature, and lasts from
2 to 72 hours.
There are two types of migraine that are:

Migraine without aura

Common migraine, associated with neurobiological disorder

Migraine with aura

Classical migraine symptoms

The occurrence of migraine varies considerably by age and gender.

Before the age of 12 years, migraine is more common in boys than in
girls, but prevalence increases more rapidly in girls after puberty.
Frequency is highest in both men and women between the ages of 25
and 45 years. The usual age of onset is 12 to 17 years of age for females
and 5 to 11 years for males, with the incidence of migraine with aura
peaking earlier in this range for both.

PATHOPHYSIOLOGY
Most clinicians now believe that the positive and negative symptoms of
the migraine aura are caused by neuronal dysfunction.
Migraine pain is believed to result from activity within the
trigeminovascular system, a network of visceral afferent fibres that arises
from the trigeminal ganglia and projects peripherally to innervate the
pain-sensitive intracranial extracerebral blood vessels, dura mater, and
large venous sinuses

Increased activity of
trigeminovascular system

Imbalance in the activity of serotonincontaining neurons and/or

noradrenergic pathways

Release of vasoactive peptides

Vasodilation
Plasma extravasation
Inflammation

Vasodilation
Activation of trigeminovascular system

Migraine is largely affected by the activity of trigeminovascular

system and also serotonin imbalance. Serotonin is known as one of the
neurotransmitter that responsible for the regulation of neural and
smooth muscle excitation, gastrointestinal motility and also pain.
Serotonin (5-HT) is primarily found in the gastrointestinal tract (GI
tract), blood platelets, and the central nervous system (CNS) of animals,
including humans.

RISK FACTORS
Migraine is believed to emerge from the following factors:

Stress

Menstruation

Exercise

Excess caffeine use or abrupt withdrawal

Foods contains MSG, cheese, chocolates

Drugs oral contraceptives, cocaine, nitroglycerin

CLINICAL FEATURES

When
untreated,
can last
from 4 to 72
hours

associated with
nausea, vomiting,
photophobia,
phonophobia
and/or sensitive to
movement

Aura:
scintillations,
photopsia,
teichopsia

SYMPTOMS
recurring episodes
of throbbing
head pain,
frequently
unilateral

Post-attack:
Exhaustion,
malaise and
irritability

10% - 60% patients experience prodromal

symptoms in hours or days before onset of
headache

SIGNS

30% of patients experience aura

(evolves over 5- 20 minutes and last less than 60 minutes)

positive family history for migraine

Presence of food triggers, menstrual association

DIAGNOSIS

CT Scan
Blood tests
MRI scan
Lumbar puncture

PHARMACOTHERAPY OF MIGRAINE
Treatment goals:

Reduce attack frequency and severity

Reduce disability

Improve quality of life

Prevention of headache

Avoid headache medicine overuse (headache rebound)

Educate and enable patients to manage the disease

Treatment choices:
1.

2.

Acute abortive therapy

Simple analgesics

NSAIDs

Opioids

Ergotamine

Triptans

Antiemetic (treatment of severe nausea/vomiting)

Preventive / Prophylactic drugs

Propranolol

Pizotifen

Amitriptyline

Anticonvulsants

Pharmacological approach Acute abortive therapy and prophylactic drugs of migraine

DRUG CLASS

GENERIC NAME

TRADE NAME

Acetaminophen

Panadol

Acetaminophen + caffeine

Panadol EXTRA

Aspirin

Acerpin

Ibuprofen

Buprol-B

Naproxen sodium

Safrosyn S

Diclofenac potassium

Cataflam

Ergotamine tartrate +
caffeine

Cafergot

1st
gen

Imigran

Acute abortive therapy

Analgesics

NSAIDs

Ergot Alkaloids

Triptans

Sumatriptan
Zolmitriptan

Zomig

Naratriptan

Naramig

Rizatriptan

Maxalt

Almotriptan

Almogran

Frovatriptan

Migard

Eletriptan

Relpax

Propranolol HCl

Inderal

Pizotifen

Sandomigran

Amitriptyline HCl

Triptafen

Topiramate

Topamax

Valproic acid

Depakote

2nd

gen

Prophylaxis therapy
Beta-blocker
Migraine
prophylactic drugs

Anticonvulsants

ANALGESIC: ACETAMINOPHEN

NAME OF DRUG

ACETAMINOPHEN

BRAND NAME

Panadol

MODE OF ACTION

inhibits prostaglandin synthesis in the CNS thus

exhibiting antipyretic and analgesic properties

DRUG INTERACTION

Acetaminophen taken concomitantly with warfarin,

isoniazid, or ketoconazole may affect blood clotting and
slow down wound healing

SIDE EFFECTS

DOSE

ADULT 12 years
500mg tablets: Two 500 mg tablets orally every 4 to 6
hours, maximum of 8 tablets in 24 hours

PHARMACOKINETICS

Hepatotoxicity when taken at extreme high doses

Skin rash
Minor allergic reactions
Bleeding

ONSET
DURATION
HALF LIFE
METABOLISM
EXCRETION

: 1 to 3 hours
: 3 to 4 hours
: 1-4 hours
: Predominantly in the liver
: via urine

ANALGESIC: ACETAMINOPHEN WITH CAFFEINE

NAME OF DRUG

ACETAMINOPHEN, CAFFEINE

BRAND NAME

Panadol EXTRA

MODE OF ACTION

inhibits prostaglandin synthesis in the CNS thus exhibiting

antipyretic and analgesic properties

DRUG INTERACTION

Acetaminophen taken concomitantly with warfarin,

isoniazid, or ketoconazole may affect blood clotting and
slow down wound healing

SIDE EFFECTS

DOSE

ADULT 12 years
1 or 2 tablets, 4-6 hourly, maximum of 8 tablets per 24
hours

PHARMACOKINETICS

Hepatotoxicity when taken at extreme high doses

Skin rash
Minor allergic reactions
Bleeding
Breathing problems

ONSET
DURATION
HALF LIFE
METABOLISM
EXCRETION

: 1 to 3 hours
: 3 to 4 hours
: 1-4 hours
: Predominantly in the liver
: via urine

NSAID: ASPIRIN
NAME OF DRUG

ASPIRIN

BRAND NAME

Aceprin

MODE OF ACTION

Aceprin has anti-inflammatory, analgesics, antipyretic

effect
Aceprin will cause the inhibition of cyclooxygenase (COX)
activity

DRUG INTERACTION

Aceprin taken with anticoagulants (e.g. - warfarin) will

increase the risk of bleeding.

SIDE EFFECT

Nausea
Dyspepsia
Vomiting

DOSE

Adult : 500-1000 mg/day

PHARMACOKINETICS

10

ONSET
DURATION
HALF LIFE
METABOLISM
EXCRETION

: Unknown
: Every 4 hours
: 2 hours
: Hepatic metabolism
: Via urine

NSAID: IBUPROFEN
NAME OF DRUG

IBUPROFEN

BRAND NAME

Buprol-B

MODE OF ACTION

The drug will cause Inhibition in the synthesis of

prostaglandins in body by inhibiting COX1 and COX2.
It has anti-inflammatory, analgesic and antipyretic effects.

DRUG INTERACTION

Ibuprofen taken with Aspirin will increase the adverse

effects of the drugs.
Ibuprofen taken with Lithium will increase the effect of
lithium toxicity.

SIDE EFFECT

GI bleeding
Peptic ulceration
Constipation

DOSE

Adult and child over 12 years, initially 300-400mg 3-4 times

daily, increased if necessary to 2.4g daily.

PHARMACOKINETICS

ONSET
DURATION
HALF LIFE
METABOLISM
EXCRETION

: 30-60 min
: 4-6 hours (orally)
: 2-4 hours
: Hepatic metabolism via oxidation
: Via urine and faeces

11

NSAID: NAPROXEN SODIUM

12

NAME OF DRUG

NAPROXEN SODIUM

BRAND NAME

Safrosyn S

MODE OF ACTION

Naproxen works by reversibly inhibiting both the COX1 and

COX2

DRUG INTERACTION

The drug can interact with antidepressant like Selective

Serotonin Reuptake Inhibitor and Lithium
It also react with Angiotensin-Converting-Enzyme (ACE)
inhibitor and Aspirin which will cause an increased risk of
bleeding

SIDE EFFECT

Constipation
Gastrointestinal disturbance
Nausea

DOSE

Adult : 220 mg orally every 8 hours as needed.

PHARMACOKINETICS

ONSET
DURATION
HALF LIFE
METABOLISM
EXCRETION

: Unknown
: Unknown
: 12-24 hours
: Hepatic metabolism
: Via urine and faeces

NSAID: DICLOFENAC POTASSIUM

NAME OF DRUG

DICLOFENAC POTASSIUM

BRAND NAME

Cataflam

MODE OF ACTION

Cataflam has anti-inflammatory, antipyretic and

analgesics action
It also thought to be inhibiting prostaglandin synthesis
by inhibition of cyclooxygenases
It also appear to exhibit bacteriostatic activity by
inhibiting bacterial DNA synthesis

DRUG INTERACTION

The drug may interact with ACE inhibitors such as

captopril which will cause a serious side effect.
Cataflam taken with anti-platelet drug such as
Clopidogrel will increase the risk of bleeding.

SIDE EFFECT

Headache
Vertigo
Abdominal pain

DOSE

Adult : 50-150 mg/day in divided doses

PHARMACOKINETICS

ONSET
DURATION
HALF LIFE
METABOLISM
EXCRETION

: Unknown
: 6-8 hours
: 1.5-2 hours
: Hepatic metabolism
: Via bile and into urine

13

ERGOT ALKALOID: ERGOTAMINE TARTRATE

14

NAME OF DRUG

ERGOTAMINE TARTRATE, CAFFEINE

BRAND NAME

Cafergot

MODE OF ACTION

Agonist, partial agonist or antagonist at 5HT, 5HT2,

adrenergic and dopaminergic receptors
Exhibiting vasoconstrictive properties and inhibit the
activity of trigeminovascular system

DRUG INTERACTION

The drug may interact with other heart-rate and blood

pressure increasing drugs thus causing exacerbation of
other cardiovascular diseases

SIDE EFFECT

Nausea, vomiting, stomach upset, restlessness, insomnia, or

dizziness

DOSE

Adult : 1-2 tablets at onset; max. 4 tablets in 24 hours.

not to be repeated at intervals of less than 4 days.
Max: 8 tablets/week

PHARMACOKINETICS

ONSET
DURATION
HALF LIFE
METABOLISM
EXCRETION

: Unknown
: Unknown
: Approximately 21 hours
: Hepatic metabolism
: Via bile

TRIPTANS: SUMATRIPTAN
NAME OF DRUG

SUMATRIPTAN

BRAND NAME

Imigran

MODE OF ACTION

Sumatriptan is structurally similar to serotonin (5-HT).

Sumatriptan acts as a serotonin agonist on specific
receptor thus producing effect that similar with serotonin
effects.

DRUG INTERACTION

Sumatriptan taken with Monoamine Oxidase A (MOA)

inhibitors such as Isocarboxazid may cause death.
Sumatriptan taken along with Ergotamine medicine or
other triptans drugs will enhance the side effect.

SIDE EFFECT

Nausea and vomiting

Increase in BP and flushing
Fatigue

DOSE

Adult : Single 50-100 mg per dose

PHARMACOKINETICS

ONSET
DURATION
HALF LIFE
METABOLISM
EXCRETION

: 10-15 minutes
: Unknown
: 2.5 hours
: Metabolized by Monoamine Oxidase A
: Via bile and urine

15

TRIPTANS: ZOLMITRIPTAN

16

NAME OF DRUG

ZOLMITRIPTAN

BRAND NAME

Zomig

MODE OF ACTION

Zolmitriptan binds with high affinity to human 5-HT1B and

5-HT1D receptors leading to cranial blood vessel
constriction as it is a selective agonist of serotonin.

DRUG INTERACTION

Concomitant use of two serotonin 5-HT1D receptor agonist

such as Zolmitriptan with Almotriptan may result in additive
vasoconstrictive affects.

SIDE EFFECT

Abdominal pain
Palpitation
Dry mouth

DOSE

Adult : 2.5 mg. Max 10 mg in 24 hours.

PHARMACOKINETICS

ONSET
DURATION
HALF LIFE
METABOLISM
EXCRETION

: Unknown
: Unknown
: 3 hours
: Hepatic metabolism
: Via renal excretion

TRIPTANS: NARATRIPTAN
NAME OF DRUG

NARATRIPTAN

BRAND NAME

Naramig

MODE OF ACTION

Naratriptan acts as a selective serotonin agonist thus the

drug produce the similar effect as serotonin to reduce
migraine.

DRUG INTERACTION

Naratriptan taken with Monoamine Oxidase

Inhibitors(MAOIs) and serotonergic may result in life
threatening serotonin syndrome.

SIDE EFFECT

Nausea and vomiting

Tingling
Dry mouth

DOSE

Adult : 2.5 mg and repeated after at least 4 hours. Max 5

mg in 24 hours.

PRARMACOKINETICS

ONSET
DURATION
HALF LIFE
METABOLISM
EXCRETION

: Unknown
: Unknown
: 5-8 hours
: Hepatic metabolism
: Via renal

17

TRIPTANS: RIZATRIPTAN

18

NAME OF DRUG

RIZATRIPTAN

BRAND NAME

Maxalt

MODE OF ACTION

Rizatriptan acts as an agonist of serotonin 5-HT1B and 5HT1D receptors to induce vasoconstriction

DRUG INTERACTION

Rizatriptan taken with Monoamine oxidase inhibitors(MAOIs)

drugs may result in life threatening serotonin syndrome

SIDE EFFECT

Myalgia
Diarrhea
Hypertension

DOSE

Adult : 2.5-15 mg per dose

PHARMACOKINETICS

ONSET
DURATION
HALF LIFE
METABOLISM
EXCRETION

: Unknown
: Unknown
: 2-3 hours
: Metabolize by monoamine oxidase
: Via urine and faeces

TRIPTANS: ALMOTRIPTAN
NAME OF DRUG

ALMOTRIPTAN

BRAND NAME

Almogran

MODE OF ACTION

Almotriptan has a high affinity for serotonin 5-HT1B/1D

receptors. Binding of the drugs to the receptors will lead
to vasoconstriction of the cranial blood vessels.

DRUG INTERACTION

Almotriptan taken with CYP3A4 inhibitor such as

Ketoconazole and Itraconazole will increase the effects
and toxicity of the drugs.

SIDE EFFECT

Increase blood pressure

Drowsiness
Dry mouth

DOSE

Adult : 12.5 mg. Max 25 mg in 24 hours.

Child : Not recommended.

PHARMACOKINETICS

ONSET
DURATION
HALF LIFE
METABOLISM
EXCRETION

: Unknown
: Unknown
: 3-4 hours
: Hepatic
: Via renal elimination

19

TRIPTANS: FROVATRIPTAN

20

NAME OF DRUG

FROVATRIPTAN

BRAND NAME

Migard

MODE OF ACTION

It is a 5HT receptor agonist with high affinity for the 5HT1B or 5-HT1D receptors.
It has no significant effect on the GABA mediated
channel activity and benzodiazepine binding sites.

DRUG INTERACTION

Frovatriptan taken with Citalopram will increase the risk

of CNS adverse effect.
Frovatriptan taken with Desvenlafaxine will increase the
risk of serotonin syndrome.

SIDE EFFECT

Dry mouth
Abdominal pain
Visual disturbance

DOSE

Adult : 5 mg in 24 hours, max.

Child : Not recommended.

PHARMACOKINETICS

ONSET
DURATION
HALF LIFE
METABOLISM
EXCRETION

: Unknown
: Unknown
: 26 hours
: Hepatic metabolism
: Via renal elimination

TRIPTANS: ELETRIPTAN
NAME OF DRUG

ELETRIPTAN

BRAND NAME

Relpax

MODE OF ACTION

It is a serotonin agonist and specifically a selective 5HT1B receptor agonist.

It is believed to reduce swelling of the blood vessels
surrounding the brain.

DRUG INTERACTION

Eletriptan taken with a macrolides such as clarithromycin

may increase the effect and toxicity of the drugs.

SIDE EFFECT

Hypertension
Tachycardia
Headache and dizziness

DOSE

Adult : 40 mg repeated after 2 hours if migraine recurs.

PHARMACOKINETICS

ONSET
DURATION
HALF LIFE
METABOLISM
EXCRETION

: Unknown
: Unknown
: 4 hours
: Hepatic enzyme CYP450, CYP3A4
: Via renal elimination

21

BETA-BLOCKER: PROPRANOLOL HCl

22

NAME OF DRUG

PROPRANOLOL HCl

BRAND NAME

Inderal LA

MODE OF ACTION

Blockage of beta-adrenergic receptors thus inhibits

arterial dilatation
Believed to prevent the emergence of migraine by
inhibiting the central mechanism that trigger migraine

DRUG INTERACTION

Alpha-receptor blockers
Antihypertensive drugs
Anticholinergics

SIDE EFFECT

Dizziness, light headedness, or tiredness

Nausea, vomiting, stomach discomfort
insomnia

DOSE

Immediate-release:
Initial : 80 mg orally per day in divided doses
Maintenance : 160-240 mg/day orally in divided doses
Sustained-release:
Initial dose: 80 mg orally once a day
Maintenance dose: 160 to 240 mg once a day

PHARMACOKINETICS

ONSET
DURATION
HALF LIFE
METABOLISM
EXCRETION

: Unknown
: 1 to 2 weeks
: 45 hours
: Hepatic
: Via renal elimination

MIGRAINE PROPHYLAXIS: PIZOTIFEN

NAME OF DRUG

PIZOTIFEN

BRAND NAME

Sandomigran

MODE OF ACTION

Primarily as a preventive measure to reduce the

frequency of recurrent migraine headaches.
Pizotifen is a serotonin antagonist acting mainly at the
5HT2A and 5HT2C receptors.
Also has some activity as an antihistamine as well as
some anticholinergic activity

DRUG INTERACTION

SIDE EFFECT

Dizziness, light headedness

Hypotension, Muscle pain, Impotence

DOSE

Adults and elderly:

1.5mg daily, taken as a single dose at night or in three
divided doses. maximum of 4.5mg daily.
Max 3mg may be given as a single daily dose.
Children:
Pizotifen can be prescribed in children from 7 years old

PHARMACOKINETICS

Sedatives
Hypnotics
Alcohol
Antihistamines

ONSET
DURATION
HALF LIFE
METABOLISM
EXCRETION

: Unknown
: Unknown
: 23 hours
: Hepatic glucuronidation
: Via urine and faeces
23

MIGRAINE PROPHYLAXIS: AMITRIPTYLINE

24

NAME OF DRUG

AMITRIPTYLINE HCL

BRAND NAME

Triptafen

MODE OF ACTION

It may help improve mood and feelings of well-being,

relieve anxiety and tension, help you sleep better, and
increase your energy level.
It works by affecting the balance of certain natural
chemicals (neurotransmitters such as serotonin) in the
brain.

DRUG INTERACTION

Taking monoamine oxidase inhibitors concomitantly may

cause fatal drug interaction
Some products that may interact with this drug include:
arbutamine, disulfiram, levodopa, thyroid supplements

SIDE EFFECT

Drowsiness, dizziness, dry mouth, blurred vision,

constipation, weight gain, trouble urinating

DOSE

Adults and elderly:

10 mg orally once a day at bedtime

PHARMACOKINETICS

ONSET
DURATION
HALF LIFE
METABOLISM
EXCRETION

: 13 hours
: 12 hours
: 22.4 hours
: Hepatic (CYP2D6)
: Via renal elimination

ANTICONVULSANT: TOPIRAMATE
NAME OF DRUG

TOPIRAMATE

BRAND NAME

Topamax

MODE OF ACTION

Topiramate inhibits trigeminovascular system activity to

induce migraine headache attack

DRUG INTERACTION

This medication may decrease the effectiveness of

hormonal birth control products
Phenytoin and carbamazepine may delay topiramate
metabolism

SIDE EFFECT

Tiredness, drowsiness, dizziness, loss of coordination,

tingling of the hands/feet, loss of appetite, bad taste in your
mouth, diarrhoea, and weight loss may occur

DOSE

The recommended dose for TOPAMAX monotherapy in

adults and paediatric patients 10 years of age and older is
400 mg/day in two divided doses

PHARMACOKINETICS

ONSET
DURATION
HALF LIFE
METABOLISM
EXCRETION

: Approximately 2 hours
: 4 days
: 19-25 hours
: Hepatic
: Via renal elimination

25

ANTICONVULSANT: VALPROIC ACID

26

NAME OF DRUG

VALPROIC ACID

BRAND NAME

Depakote

MODE OF ACTION

Increases GABA level and suppresses migraine-related

events in the cortex and trigeminovascular system
Alters the excitatory and inhibitory neurotransmitter
level

DRUG INTERACTION

Antidepressants
Benzodiazepines
Antibiotics

SIDE EFFECT

Diarrhoea, dizziness, drowsiness, hair loss, blurred/double

vision, change in menstrual periods, ringing in the ears,
shakiness (tremor), unsteadiness, weight changes may
occur

DOSE

Adult : 250 mg twice daily, increased if necessary to 1g daily

in divided doses

PHARMACOKINETICS

ONSET
DURATION
HALF LIFE
METABOLISM
EXCRETION

: Unknown
: Unknown
: 11 hours
: Hepatic
: Via renal elimination

DISEASE MANAGEMENT
Basically, non-pharmacological management are methods that do not require
the uses of drugs. It is important for patient to adhere to this management
because drugs alone would not suffice to help to treat this disease, apart

form its potential to prevent migraine attacks.

Some of non-pharmacological therapy of acute migraine headaches are:

application of ice to the head

periods of rest or sleep, usually in a dark and quiet environment

Preventive measures that can be practiced are:

Identify and avoid factors that consistently provoke migraine attacks

Regular sleeping time

Exercising

Healthy eating

Smoking cessation

Limit caffeine intake

Behavioural interventions - relaxation and cognitive therapy

27

REFERENCES

Abrams A.C. (2004). Clinical Drug Therapy: Rationals for Nursing

Practice. United States of America: Lippincott Williams & Wilkins.
Clark M.A., Finkel R., Rey J.A. And Whalen K. (2012) Lippincotts
Illustrated Reviews: Pharmacology 5th Edition, United States of
America: Lippincott Williams & Wilkins.
Dipiro J.T., Talbert R.L., Yee G.C., Matzke G.R., Wells B.G., & Posey L.M.
(2008). Pharmacotherapy: A Pathophysiologic Approach 7th Edition.

United States of America: The Mc Graw-Hill Companies Inc.

Katzung B.G. (2001). Basic & Clinical Pharmacology 8th edition. United
States of America: The Mc Graw-Hill Companies Inc.

28