Download Migraine

Drugs used in Migraine
Dr.B.V.Venkataraman
Professor in Pharmacology
Faculti Perubatan,
Shah Alam, Malaysia- 40450
[email protected]
Ph:603-5544-2849/0163630196
What is a migraine?
A migraine is a throbbing, intense headache in one
half of the head.
Affect people of all ages.
Associated with anorexia, nausea and vomiting
Dilatation of cranial blood vessels causes the pain.
Migraine Triggers
Food
Changes in wake-sleep pattern
Hormonal changes (e.g.menopause)
Drugs
Physical exertion
Stress
Sensory stimuli
Environmental changes
Hunger
Psychological factors
Phases of Acute Migraine
PRODROME
AURA
HEADACHE
POSTDROME
PRODROME
Vague premonitory symptoms that begin from 12 to
36 hours before the aura and headache
Symptoms include
Yawning
Excitation
Depression
Lethargy
Craving or distaste for various foods
Duration – 15 to 20 min
AURA (absent in some people)
Aura is a warning or signal before
onset of headache
Symptoms
Flashing of lights
Zigzag lines
Difficulty in focussing
Duration : 15-30 min
HEADACHE
Headache is generally unilateral and is
associated with symptoms like:
Anorexia
Nausea
Vomiting
Photophobia (fear of light)
Phonophobia (fear of sound)
Tinnitus
Duration is 4-72 hrs
POSTDROME (RESOLUTION PHASE)
Following headache, patient complains of
Fatigue
Depression
Severe exhaustion
Some patients feel unusually fresh
Duration: Few hours or up to 2 days
MIGRAINE – CLASSIFICATION
According to Headache Classification Committee of the
International Headache Society, Migraine has been
classified as:
Migraine without aura (common migraine)
Migraine with aura (classic migraine)
Complicated migraine
MIGRAINE: CLINICAL FEATURES
Migraine Without Aura
Migraine With Aura
No aura or Prodrome
Aura or prodrome is
present
Unilateral throbbing headache Unilateral throbbing headache
may be accompanied by
and later becomes
nausea and vomiting
generalised
During headache, patient
complains of phonophobia
and photophobia
Patient complains of visual
disturbances and may have
mood variations
MIGRAINE - PATHOPHYSIOLOGY
VASCULAR THEORY
Intracerebral blood vessel vasoconstriction – aura
Intracranial/Extracranial blood vessel vasodilation –
headache
Vascular Theory
MIGRAINE - PATHOPHYSIOLOGY
Serotonin Theory
Decreased serotonin levels linked to migraine
Specific serotonin receptors found in blood vessels
of brain
Present Understanding
Neurovascular process, in which neural events
result in activation of blood vessels, which in turn
results in pain and further nerve activation
Arterial
Activation
Release of
Neurotransmitter
Worsening of Pain
calcitonin gene-related
peptide /Nitric oxide
MIGRAINE MANAGEMENT
Non-pharmacological treatment
Identification of triggers
Meditation
Relaxation training
Psychotherapy
Pharmacotherapy
non-specific
Abortive therapy
specific
Preventive therapy
MIGRAINE: ABORTIVE THERAPY
Non-specific treatment
Drug
Dose
Route
Aspirin
500-650 mg
Oral
Paracetamol
500 mg-4 g
Oral
Ibuprofen
200- 300 mg
Oral
Diclofenac
50-100 mg
Oral/IM
Naproxen
500-750 mg
Oral
NSAIDs
Relieve mild migraines
Inhibition of PG
Chronic use leads to ulcers, gastrointestinal
bleeding and rebound headaches.
ABORTIVE THERAPY FOR MIGRAINE
Specific treatment
Drug
Dose
Route
Ergot alkaloids
Ergotamine
1-2 mg/d; max-6
g/d
Dihydroergotamine 0.75-1 mg
Oral
SC
5-HT receptor agonists
Sumatriptan
25-300 mg
6 mg
Orally
SC
nasal
Rizatriptan
10 mg
Orally
ERGOTS
Ergotamine alkaloid from the fungus, claviceps
purpurae
Non-selective 5HT agonist & alpha blocker
Constriction of cranial arteries
Caffeine added to increase the absorption from GIT
Nausea, vomiting, diarrhoea – common side effect
Dihydroergotamine – more effective with lesser side
effect – also available as nasal drops
TRIPTANS
Severe attack
Relieve pain, nausea, phonophobia, photophobia that
are associated with attack
5-HT1B (blood vessels) and 5-HT1D (trigeminal)
receptors agonist
Sumatriptan: nasal, sc preparation avoid Gastric
irritation
rizatriptan, naratriptan, zolmitriptan, almotriptan,
frovatriptan, eletriptan
Side effects: nausea, dizziness, muscle weakness.
Coronary vasoconstriction, heart attack and rarely
stroke
ANTI-NAUSEANT DRUGS FOR MIGRAINE
TREATMENT
Drug
Dose (mg)/d
Route
Domperidone
10-80 mg
Oral
Metoclopramide
5-10 mg
Oral/IV
Promethazine
50-125 mg
Oral/IM
Chlorpromazine
10-25 mg
Oral/IV
Anti-nausea medications
Attacks usually accompanied by nausea, vomiting
Medication for these symptoms appropriate
combined with other medication
WHY THE NEED FOR PROPHYLAXIS ?
Abortive drugs should not be used more than 2-3
times a week
Long-term prophylaxis improves quality of life by
reducing frequency and severity of attacks
80% of migraineurs may require prophylaxis
PREVENTIVE THERAPY FOR MIGRAINE
Drugs
1.
Betablockers
– Propranolol
2.
Calcium Channel
Blockers
– Flunarizine
– Verapamil
3.
40-320
10-20
120-480
TCAs
– Amitriptyline
4.
Dose (mg/d)
10-20
SSRIs
– Fluoxetine
20-60
PROPRANOLOL – MECHANISMS OF ACTION
Mechanisms proposed
Vasoconstriction
Anxiolytic action
Decrease sympathetic activity
CALCIUM CHANNEL BLOCKERS
Flunarizine, Verapamil
Vasodilatation due to calcium channel blocking
Common side effects: constipation and postural
hypotension.
ANTI DEPRESSANTS
Tricyclic antidepressants: effective
Amitriptyline, nortriptyline, protriptyline: commonly
used
All types of headache including migraine
Patient need not have depression
PREVENTIVE THERAPY FOR MIGRAINE (CONTD.)
Drugs
5. Anti-convulsant
– Sodium valproate
6. Anti-histaminic
– Cyproheptadine
Dose (mg/d)
600-1200
4-8
ANTI SEIZURE DRUGS
Drugs with dual property (anti-seizure and bipolar
depression): useful
5HT Antagonist
Cyproheptadine: antihistaminic, Calcium antagonist
Methysergide: rarely used because of risk of
retroperitoneal fibrosis and renal failure.
Anti-hypertensive
Clonidine: Alpha-2 agonist
Botulinum toxin type A
Used in wrinkles