Headache

Introduction
• Migraine is a syndrome that affects a significant
fraction of the world population, with a higher
prevalence in women (15%) than in men (6%)
• Characterized by
– an intense and throbbing unilateral headache
• associated with anorexia, nausea, vomiting,
photophobia, and/or diarrhea.
 THEORIES IN THE EARLY 20TH
CENTURY

• During a significant number of migraine attacks,

 pain could be relieved either by physical
compression or by ergotamine
• Establish the vascular theory of migraine
beyond any doubt
• Trigeminal nerve and the cranial vasculature
 HISTORY…

• trigeminovascular axons from blood vessels of

the pia mater and dura mater release vasoactive
peptides producing a sterile inflammatory
reaction with pain
• trigeminal ganglion is stimulated and this
induces neurogenic protein extravasation
• some vasodilator peptides are released,
including CGRP, substance P and neurokinin A
 VASCULAR OR NEUROGENIC THEORY ?

• no definitive evidence thus far to categorically

exclude the vascular or the neurogenic theories
all acute antimigraine drugs invariably
produce both cranial (carotid)
vasoconstriction (shown in animals and
humans) and
inhibition of the trigemino-vascular system
(centrally and/or peripherally; shown only
in rats and guinea-pigs)
 MIGRAINE PATHOPHYSIOLOGY

• three distinct phases can be discerned:

• an initiating trigger, an aura and, finally, the
headache
• brainstem as ‘migraine generator’
• once the "migraine generator" has been switched
on, regional cerebral blood flow decreases
• aura symptoms may appear
 PATHO…

• then followed by a vasodilatation during

headache
• probably due to changes in the activity of the
neurones innervating cranial arteries
• cranial vasodilatation leads to enhanced blood
volume following each cardiac stroke
• consequent augmentation in pulsations within
the affected blood vessels
• sensed by "stretch" receptors in the vessel wall
 PATHO...

• the resultant increase in perivascular

(trigeminal) sensory nerve activity provokes
headache and other symptoms
• This trigeminal stimulation may also release
neuropeptides, thus reinforcing vasodilatation
and perivascular nerve activity
 Migraine Without Aura (Common
Migraine)
• Most common cause of
migraine (80%)
• D. During headache
• A.At least five attacks with
the criteria B,C,D, and E
associated with
nausea/vomiting or
• B. Attack lasts 4 to 72 hours
with or without treatment photophobia/phonopho
• C. Has two of the following: bia
unilateral location, pulsating • E. History, physical and
quality, and moderate to diagnostic tests that
severe intensity, aggravated exclude related organic
by activity
disease
 Migraine with Aura (Classic Migraine)
A. At least two attacks that fulfill criterion B
B. At least three of the four characteristics:
1. one or more reversible aura symptoms
2. at least one aura develops gradually over more than
4 minutes
3. no single aura lasts longer than 60 minutes
4. headache begins during aura or follows with a
symptom-free interval of less than 60 minutes
C. An appropriate history, physical, and diagnostic tests that
exclude related organic disease.
 Clinical Features
• Most common aura is visual
a)scintillating scotomas
b)photopsias
c)teichopsias
d)blurred vision
• Less common auras are somatosensory
a)tingling or numbness
b)motor disturbances
c)cognitive disturbances
 Clinical Features
• Ophthalmoplegic migraine
is a rare condition
associated with paresis of
ocular nerves that may last
days to weeks
• Hemiplegic migraine is
characterized by episodic
hemiparesis or hemiplegia
as an aura that is slow or
marching in progression and
lasts 30 to 60 minutes
• Basilar artery migraine
arises with an aura
referable to brainstem and
associated with near
blindness, dysarthria,
tinnitus, vertigo, bilateral
paresthesias, or altered
consciousness
• Status migrainosus persists
longer than 72 hours and
requires pain management
 Treatment-Abortive
Mild to Moderate Moderate to Severe Refractory Attack,
Attacks Attacks
Status Migrainosus
Acetaminophen Dihydroergotamine(1mg Dihydroergotamine
Aspirin IV or IM), may repeat 1 Steroids
Ibuprofen hr
Naprosyn Sumatriptan,(6 mg SC/
25-100mg PO)
Rizatriptan, Naratriptan,
Zolmitriptan,
Prochlorpethazine
Metaclopromide
Ketorolac, Meperidine
 Treatment-Prophylactic
• More than 2-3 episodes a month, prolonged
attacks, severe and debilitating
First line agents
*b-blockers like propanolol
*tricyclic antidepressants (esp. amitryptyline)
Second line agents
*calcium channel blockers (Flunarizine)
*depakote
*monoamine oxidase inhibitors
 TREATMENT OF MIGRAINE

• divided into two groups:

• acute antimigraine and prophylactic drugs
Acute Antimigraine Drugs
Non-specific Drugs:
• used to treat the symptoms accompanying the
headache
• Antiemetics (metoclopramide), NSAID’s; e.g.
aspirin) and anxyolitics/sedatives (chlorpromazine)
 TREATMENT…

Specific Drugs
• abolish the headache by producing selective
vasoconstriction of extracranial blood vessels
• ergot alkaloids, ergotamine and
dihydroergotamine
MOA OF ERGOTAMINE AND DIHYDROERGOTAMINE

• produce external carotid vasoconstriction

• interact with 5-HT1, 5-HT2, 5-HT5, 5-HT6, 5-T7, a-
adrenoceptors and dopamine receptors
• Responses were partially blocked by GR127935 (5-
HT1B/1D recep. Anta), or by yohimbine (a2-AR anta)
• vasoconstrictor responses to these drugs abolished
when combined
• confirming that 5-HT1B/1D receptors and a2
adrenoceptors are involved
 SUMATRIPTAN

• clinical use of 5-HT

– Changes in heart rate,
– vasodilatation in some vascular beds (e.g.
cutaneous blood vessels)
– vasoconstriction in others (e.g. the external
carotid bed)
– gastrointestinal effects
 SUMATRIPTAN

• After analysing several tryptamine derivatives, 3-

[2-(di-methylamino) ethyl]-N-methyl-1H-indole-
5-methane sulphonamide (sumatriptan)
• Producing vasoconstriction in the dog
extracranial blood vessels
• is an agonist at 5-HT1B/1D receptors
• mediates constriction of cranial large arteries
(i.e. the external carotid bed)
 EXPERIMENTAL MODELS

• are based on the vascular or neurogenic theories of

migraine
Models Based on the Involvement of Cranial
Vasodilatation in Migraine
• consider cranial vasodilatation as an integral part of the
pathophysiology of migraine
• ergot alkaloids and sumatriptan owe their therapeutic
efficacy primarily to the constriction of dilated vessels
• Contraction of isolated cranial blood vessels
more marked on cranial blood vessels (5-HT1B)
 

 Trigeminovascular System Based Models

• Inhibition of plasma protein extravasation after
stimulation of the trigeminal nerve in the rat
and guinea pig
sumatriptan inhibits neurogenic plasma protein
extravasation
antagonised by the 5-HT1B/1D receptor antagonist
GR127935
 PHARMACOLOGY OF SUMATRIPTAN AND
SECOND-GENERATION TRIPTANS

• Zolmitriptan, rizatriptan and naratriptan

• referred to as the second-generation triptans b/c
tryptamine derivatives
pharmacologically comparable to
sumatriptan
 RECEPTOR BINDING PROFILE OF TRIPTANS

• high affinities at 5-HT1 receptors, mainly the 5-

HT1B and 5-HT1D receptors
• With the exception of rizatriptan and
almotriptan and, to some extent sumatriptan, all
others have high affinity at the 5-HT1A receptor.
 FUTURE TRENDS IN THE EFFICACY OF
ANTIMIGRAINE DRUGS

• sumatriptan and the second-generation triptans:

5-HT1B receptor, associated with acute
treatment of migraine
• 5-HT1B receptor, being not exclusively
confined to cranial blood vessels
• responsible for the moderate hypertension and
coronary constriction
• Future solution: 5-HT1D or F receptor agonists
 Cluster Headache
• More common in men
• Associated with several episodes over 24 hrs
that can last minutes up to 2 hrs
• Clinical features include
-unilateral sharp stabbing pain in eye
-involves the distribution of CN V
(trigeminal nerve)
-30% of patients have partial Horner’s syn.
-eye is often injected, tearing
 Cluster Headache-Treatment
• High flow oxygen of 7-10 l/min
• Sumatriptan, DHE
• Prednisone tapering dose
• Sphenopalatine nerve anesthesia with
intranasal cocaine or lidocaine-controversial
 Tension Headache
• Most common type of headache
• Higher prevalence in middle aged women
• Usual frequency is 5 episodes per month
• Clinical features include
-tight, band-like discomfort around the head
-intensity of pain is not severe and thus not
debilitating
-headache does not worsen with physical
activity
-coexisting anxiety and depression are
common
 Tension headache-Treatment
• Aspirin, acetaminophen, NSAIDs
• Exercise program
• Nonpharmacologic regimen like massage,
meditation, and biofeedback
• Psychotherapy
 Medication-Induced Headache
• Medication use, abuse or • Patients build tolerance
withdrawal is the cause.
to the meds and
• Common in patients with
chronic headache disorders subsequently require
like migraine or tension- higher doses for
type. symptomatic relief.
• Most common meds
include ASA, NSAIDs, • Treatment includes
paracetamol, barbiturate- withdrawal of the
analgesic combinations, overused medications
caffeine, and ergotamine
 Carbon Monoxide Poisoning
• Usually gradual, subtle, dull, nonfocal throbbing pain
associated with nausea, chest pain.
• Symptoms may wax and wane as patients may enter
and leave the area of carbon monoxide
• Exposure to engine exhaust, old or defective heating
systems, most common in winter months.
• Diagnosis is made by elevated carboxyhemoglobin
• Treatment is oxygen
 High Altitude Headache
• Main symptom of Acute Mountain Sickness
• Can occur at altitudes higher than 5000 feet in
unacclimatized individuals.
• HA is throbbing, located in temporal or
occipital area and worsens at night or early in
the morning.
• Treatment includes supplemental oxygen and
descent to a lower altitude.
National drug list of Ethiopia, 2010
• Acetylsalicylic Acid+ Paracetamol +Caffeine Tablet,
250mg + 250mg + 65mg
• Ergotamine Tartrate Injection, 0.25mg/ml in 1ml
ampoule; Tablet, 1mg, 2mg (sublingual)
• Ergotamine Tartrate + Caffeine Tablet 1mg +100mg;
Suppository, 2mg +100mg
• Ergotamine Tartrate + Caffeine Hydrate + Cyclizine
Hydrochloride Tablet, 2mg +50mg +100mg
• Propranolol Tablet, 10mg, 20mg, 40mg, 60mg, 80mg
• Sumatriptan Tablet, 50mg, 100mg; Injection,
12mg/ml; Nasal spray, 20mg/0.1ml
 Other causes of headache
• Postdural Puncture Headache
• Acute Glaucoma
• Posttraumatic Headache
• Idiopathic Intracranial Hypertension
• Subarachnoid Hemorrhage (SAH)
• Brain tumor
THANK YOU!!!