migraine booklet

UNIVERSITI TEKNOLOGI MARA PULAU PINANG

KAMPUS BERTAM

FACULTY OF PHARMACY

MIGRAINEand what you should know

Mohd Redza bin Mohd Hanif

Muhamad Illias bin Mohamad

Ahmad Khairul Azwar bin Sukeri

Fatin Nur Nazihah binti Zainuddin

Hazatul Syifaa binti Mahamad Esha

I’m always

getting

headaches.

Is it

migraine?

AU

TH

OR

S

TABLE OF CONTENTS

1. Migraine – The Introduction 1

2. Pathophysiology of Migraine 2

3. Risk Factors of Migraine 3

4. Clinical Features of Migraine 4 – 5

5. Pharmacotherapy – Drugs 6 – 26

6. Disease Management 27

7. References 28

i

1

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

Imbalance in the activity of serotonin-

containing neurons and/or

noradrenergic pathways

Vasodilation

Activation of trigeminovascular system

Increased activity of

trigeminovascular system

Release of vasoactive peptides

Vasodilation

Plasma extravasation

Inflammation

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.

2

3

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

recurring episodes

of throbbing

head pain,

frequently

unilateral

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

Post-attack:

Exhaustion,

malaise and

irritability

4

5

SIGNS

10% - 60% patients experience prodromal

symptoms in hours or days before onset of

headache

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

• CT Scan

• Blood tests

• MRI scan

• Lumbar puncture

DIAGNOSIS

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. Acute abortive therapy

• Simple analgesics

• NSAIDs

• Opioids

• Ergotamine

• Triptans

• Antiemetic (treatment of severe nausea/vomiting)

2. Preventive / Prophylactic drugs

• Propranolol

• Pizotifen

• Amitriptyline

• Anticonvulsants

6

7

DRUG CLASS GENERIC NAME TRADE NAME

Acute abortive therapy

Analgesics

Acetaminophen Panadol

Acetaminophen + caffeine Panadol EXTRA

NSAIDs

Aspirin Acerpin

Ibuprofen Buprol-B

Naproxen sodium Safrosyn S

Diclofenac potassium Cataflam

Ergot AlkaloidsErgotamine tartrate +

caffeineCafergot

Triptans

1st

genSumatriptan Imigran

2nd

gen

Zolmitriptan Zomig

Naratriptan Naramig

Rizatriptan Maxalt

Almotriptan Almogran

Frovatriptan Migard

Eletriptan Relpax

Prophylaxis therapy

Beta-blocker Propranolol HCl Inderal

Migraine

prophylactic drugs

Pizotifen Sandomigran

Amitriptyline HCl Triptafen

Anticonvulsants

Topiramate Topamax

Valproic acid Depakote

Pharmacological approach – Acute abortive therapy and prophylactic drugs of migraine

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

• Hepatotoxicity – when taken at extreme high doses

• Skin rash

• Minor allergic reactions

• Bleeding

DOSE

ADULT ≥ 12 years

500mg tablets: Two 500 mg tablets orally every 4 to 6

hours, maximum of 8 tablets in 24 hours

PHARMACOKINETICS

• ONSET : 1 to 3 hours

• DURATION : 3 to 4 hours

• HALF LIFE : 1-4 hours

• METABOLISM : Predominantly in the liver

• EXCRETION : via urine

8

ANALGESIC: ACETAMINOPHEN WITH CAFFEINE

9

NAME OF DRUG ACETAMINOPHEN, CAFFEINE

BRAND NAME Panadol EXTRA

MODE OF ACTIONinhibits 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

• Hepatotoxicity – when taken at extreme high doses

• Skin rash

• Minor allergic reactions

• Bleeding

• Breathing problems

DOSE

ADULT ≥ 12 years

1 or 2 tablets, 4-6 hourly, maximum of 8 tablets per 24

hours

PHARMACOKINETICS

• ONSET : 1 to 3 hours

• DURATION : 3 to 4 hours


• METABOLISM : Predominantly in the liver

• EXCRETION : 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 INTERACTIONAceprin taken with anticoagulants (e.g. - warfarin) will

increase the risk of bleeding.

SIDE EFFECT

• Nausea

• Dyspepsia

• Vomiting

DOSE Adult : 500-1000 mg/day

PHARMACOKINETICS

• ONSET : Unknown

• DURATION : Every 4 hours

• HALF LIFE : 2 hours

• METABOLISM : Hepatic metabolism

• EXCRETION : Via urine

10

NSAID: IBUPROFEN

11

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

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

daily, increased if necessary to 2.4g daily.

PHARMACOKINETICS

• ONSET : 30-60 min

• DURATION : 4-6 hours (orally)


• METABOLISM : Hepatic metabolism via oxidation

• EXCRETION : Via urine and faeces

NSAID: NAPROXEN SODIUM

NAME OF DRUG NAPROXEN SODIUM

BRAND NAME Safrosyn S®

MODE OF ACTIONNaproxen 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 : Unknown

• DURATION : Unknown




12

NSAID: DICLOFENAC POTASSIUM

13

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 : Unknown

• DURATION : 6-8 hours

• HALF LIFE : 1.5-2 hours


• EXCRETION : Via bile and into urine

ERGOT ALKALOID: ERGOTAMINE TARTRATE

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 EFFECTNausea, 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 : Unknown


• HALF LIFE : Approximately 21 hours


• EXCRETION : Via bile

14

TRIPTANS: SUMATRIPTAN

15

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 : 10-15 minutes


• HALF LIFE : 2.5 hours

• METABOLISM : Metabolized by Monoamine Oxidase A

• EXCRETION : Via bile and urine

TRIPTANS: ZOLMITRIPTAN

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 : Unknown




• EXCRETION : Via renal excretion

16

TRIPTANS: NARATRIPTAN

17

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

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

mg in 24 hours.

PRARMACOKINETICS

• ONSET : Unknown




• EXCRETION : Via renal

TRIPTANS: RIZATRIPTAN

NAME OF DRUG RIZATRIPTAN

BRAND NAME Maxalt®

MODE OF ACTIONRizatriptan acts as an agonist of serotonin 5-HT1B and 5-

HT1D receptors to induce vasoconstriction

DRUG INTERACTIONRizatriptan 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 : Unknown



• METABOLISM : Metabolize by monoamine oxidase


18

TRIPTANS: ALMOTRIPTAN

19

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

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

Child : Not recommended.

PHARMACOKINETICS

• ONSET : Unknown



• METABOLISM : Hepatic

• EXCRETION : Via renal elimination

TRIPTANS: FROVATRIPTAN

NAME OF DRUG FROVATRIPTAN

BRAND NAME Migard®

MODE OF ACTION

• It is a 5HT receptor agonist with high affinity for the 5-

HT1B 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

DOSEAdult : 5 mg in 24 hours, max.

Child : Not recommended.

PHARMACOKINETICS

• ONSET : Unknown





20

TRIPTANS: ELETRIPTAN

21

NAME OF DRUG ELETRIPTAN

BRAND NAME Relpax®

MODE OF ACTION

• It is a serotonin agonist and specifically a selective 5-

HT1B receptor agonist.

• It is believed to reduce swelling of the blood vessels

surrounding the brain.

DRUG INTERACTIONEletriptan 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 : Unknown



• METABOLISM : Hepatic enzyme CYP450, CYP3A4


BETA-BLOCKER: PROPRANOLOL HCl

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 : Unknown

• DURATION : 1 to 2 weeks

• HALF LIFE : 4–5 hours



22

MIGRAINE PROPHYLAXIS: PIZOTIFEN

23

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

• Sedatives

• Hypnotics

• Alcohol

• Antihistamines

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

• ONSET : Unknown



• METABOLISM : Hepatic glucuronidation


MIGRAINE PROPHYLAXIS: AMITRIPTYLINE

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 EFFECTDrowsiness, dizziness, dry mouth, blurred vision,

constipation, weight gain, trouble urinating

DOSEAdults and elderly:

10 mg orally once a day at bedtime

PHARMACOKINETICS

• ONSET : 1–3 hours

• DURATION : 12 hours

• HALF LIFE : 22.4 hours

• METABOLISM : Hepatic (CYP2D6)


24

ANTICONVULSANT: TOPIRAMATE

25

NAME OF DRUG TOPIRAMATE

BRAND NAME Topamax®

MODE OF ACTIONTopiramate 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 : Approximately 2 hours

• DURATION : 4 days




ANTICONVULSANT: VALPROIC ACID

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

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

in divided doses

PHARMACOKINETICS

• ONSET : Unknown





26

DISEASE MANAGEMENT

27

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

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) Lippincott’s

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

migraine booklet

Documents

migraine pain

auracommon migraine

incidence of migraine

types of migraine

pathophysiology of migraine

risk factors of migraine

clinical features of

activity of serotonin