migraine booklet
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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
• HALF LIFE : 1-4 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)
• HALF LIFE : 2-4 hours
• 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
• HALF LIFE : 12-24 hours
• METABOLISM : Hepatic metabolism
• EXCRETION : Via urine and faeces
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
• METABOLISM : Hepatic metabolism
• 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
• DURATION : Unknown
• HALF LIFE : Approximately 21 hours
• METABOLISM : Hepatic metabolism
• 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
• DURATION : Unknown
• 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
• DURATION : Unknown
• HALF LIFE : 3 hours
• METABOLISM : Hepatic metabolism
• 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
• DURATION : Unknown
• HALF LIFE : 5-8 hours
• METABOLISM : Hepatic metabolism
• 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
• DURATION : Unknown
• HALF LIFE : 2-3 hours
• METABOLISM : Metabolize by monoamine oxidase
• EXCRETION : Via urine and faeces
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
• DURATION : Unknown
• HALF LIFE : 3-4 hours
• 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
• DURATION : Unknown
• HALF LIFE : 26 hours
• METABOLISM : Hepatic metabolism
• EXCRETION : Via renal elimination
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
• DURATION : Unknown
• HALF LIFE : 4 hours
• METABOLISM : Hepatic enzyme CYP450, CYP3A4
• EXCRETION : Via renal elimination
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
• METABOLISM : Hepatic
• EXCRETION : Via renal elimination
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
• DURATION : Unknown
• HALF LIFE : 23 hours
• METABOLISM : Hepatic glucuronidation
• EXCRETION : Via urine and faeces
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)
• EXCRETION : Via renal elimination
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
• HALF LIFE : 19-25 hours
• METABOLISM : Hepatic
• EXCRETION : Via renal elimination
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
• DURATION : Unknown
• HALF LIFE : 11 hours
• METABOLISM : Hepatic
• EXCRETION : Via renal elimination
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
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