IN THE NAME OF

ALLAH
THE MOST BENIFICIENT
THE MOST MERCIFUL

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 HEADACHES

Chronic headaches are commonly due to

Migraine, Tension or Depression.
They may be related to
 Sinusitis
 Head injury
 Hypertension
 Dental disease
 Ocular disease
 Intracranial lesions,
 Cervical spondylitis,
 Temporo-mandibular joint dysfunction.

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 HEADACHES

Identified by:
 Quality
 Intensity
 Site of pain
 Duration of pain
 Neurological
symptoms

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 MIGRAINE

Migraine is a form of headache,

Characterized by:
 Periodic,
 Severe,
 Unilateral headache,
 Spreading from behind the eye.

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 Migraine headache is
 Constant
 Throbbing
 Pulsating
and may accompanied by
 Photophobia,
 Phonophobia
 Nausea
 Vomiting.
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 Migraine Symptoms and Stages
 Stage 1 (Prodrome) Prodrome symptoms may occur
days before actual pain. Characterized by symptoms of
light, sound sensitivity, depression and Irritability.

 Stage 2 (Aura) Auras usually occur up to one hour prior

to headache. Symptoms include seeing flashing lights,
geometric patterns, or temporary loss of vision.

 Stage 3 (Headache) Headache pain moderate to severe,

lasting up to three days. Intolerance of light and noise,
nausea, vomiting, Speech difficulties.

 Stage 4 (Postdrome) can last for several days, called

“migraine hangover” irritable and fatigue, tender scalp.
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 Types of Migraine

 Classic Migraine ( migraine with aura ):

Headache preceded by neurological symptoms (aura),
which can be visual, sensory, and can cause
speech or motor disturbances.

 Common Migraine ( migraine without aura ):

It is severe, unilateral, pulsating headache,
that typically lasts from 2 to 72 hours.
Aggravated by physical activity.
Accompanied by nausea, vomiting, photophobia,
phonophobia.
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 Patho-Physiology of Migraine

 Migraine involves the trigeminal nerve distribution to

intracranial and extracranial arteries.
 These nerves release peptide neurotransmitters especially
Calcitonin Gene-Related Peptide, ( a powerful vasodilator ),
Substance-P and Neurokinin may also be involved.
 Extravasation of plasma and plasma proteins into the
perivascular space appears.
 Perivascular edema causes mechanical stretch, which may
be the immediate cause of activation of pain nerve endings,
and pain associate with temporal artery.
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 Patho-Physiology of Migraine

It is believed that migraine is due to vasoconstriction

followed by vasodilatation and
edema of the cranial arteries.

The onset of pain associated

with marked increase in
amplitude of temporal artery
pulsation

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 DRUGS USED IN MIGRAINE

The mechanism of action of drugs used in

migraine are poorly understood

5-HT agonist
Triptans

Β-blockers
Ergot alkaloids NSAIDS Ca++ Blockers

Tricyclic
antidepressants Anti-seizures

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 DRUGS USED IN MIGRAINE

1. Drugs For Acute Attack

 Triptans = Almotriptan, Sumatriptan, Naratriptan,
Rizatriptan , Eletriptan, Frovatriptan, Zolmitriptan
 Ergotamine tartrate, Dihydroergotamine
 Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)

2. Drugs For Prophylaxis

 Methysergide
 Beta-blockers, Ca++ Blockers
 Tricyclic Anti-depressants
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 Actions

Two primary hypothesis are there

1. 5-HT agonists (Trpitans), and Anti-depressants

may activate 5-HT1D /1B receptors on presynaptic
trigeminal nerve endings, to inhibit the release of
vasodilator peptides, and
anti-seizure agents may suppress excessive firing
of these nerve endings.

2. Vasoconstrictor action of direct 5-HT agonists may

prevent vasodilatation & stretching of pain endings.
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 SUMATRIPTAN

 used as first-line therapy for acute migraine attacks,

 Markedly reduces the severity of migraine headaches,
 It is a serotonin agonist, acting at 5-HT1D receptors.
These receptors found on small nerves that
innervate the intracranial vasculature.
Their activation probably suppresses release
of sensory neuropeptides, such as substance-P.
 Used orally, subcutaneously and by nasal spry,
 Has short duration of action,
 Half-life 2-3 hours.
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 SUMATRIPTAN
 Adverse effects: mostly mild, include
altered sensations ( tingling, warmth ), dizziness,
muscle weakness, neck pain, injection site reaction.

Contraindications: Not used in patient with coronary

artery disease eg (due to coronary vasospasm).
Naratriptan and Eletriptan are contraindicated in
severe hepatic and renal impairment, peripheral
vascular disease
Disadvantages: Short duration of action & expensive.
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 ERGOTAMINE

 Ergot derivatives ( Bromocriptine, Ergonovine,

Ergotamine, Lysergic acid diethylamide,
Methysergide ) are highly specific for migraine pain.

 They are not analgesic for other conditions.

 Available for oral, sublingual, rectal & inhaler use.

 Absorption of ergotamine increased when used with

caffeine, 100 mg caffeine for each 1 mg ergotamine )

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 ERGOTAMINE

Mode of action: Act on several types of receptors.

Vasoconstriction of cranial arteries by direct action
on the vessel walls,

 Vasoconstriction induced by ergotamine is

long-lasting (alpha blocking action) and cumulative.
(no ˃ 6 mg /attack, no ˃ 10 mg/ weak )

 The reduction in the amplitude of their pulsation is

believed to be responsible for the relief of acute
migraine attack.
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 ERGOTAMINE

Side effects:
 Nausea, vomiting, Diarrhea,
 Numbness of fingers and toes,
 Anginal pain,
 Abortion if given in pregnancy,
 Gangrene due to over dose,
 Bowel infarction.
Contraindications:
 Peripheral vascular diseases,
 Hypertension,
 Coronary heart disease.
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 METHYSERGIDE

 It is ineffective in the treatment of active episode of

migraine.

 Was used for migraine prophylaxis ,

 Was withdrawn because of toxicity.

 Chronic use may cause retroperitoneal fibroplasia and

subendocardial fibrosis.

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 DRUGS USED IN MIGRAINE

 NSAIDs:
Anti-inflammatory analgesics, Aspirin and Ibuprofen
are often help full in controlling the pain of migraine.

 Opioids :
Rarely parenteral Opioids may be needed,
Codeine some times used to treat migraine pain,
when people can not take triptans or ergot.

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 β -Blockers
PROPRANOLOL

 β-blockers are currently used for the prophylactic

treatment of migraine.

 Mechanism of action is not understood, but they

involve in blockade of Cranio-vascular β-receptors
that results in reduced vasodilatation.
(block catecholamine-induced vasodilatation )

 By this way β-blockers decreases the frequency and

severity of the attacks of migraine.

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 Calcium Channel Blockers

 They block the effect of the Serotonin that operates

within nerves. Serotonin leads to contracting,
tightening of the blood vessels in the head and also
lowers a person’s tolerance for pain.
 Therefore calcium blockers are believed to prevent
migraines by interrupting the action of serotonin.
 Verapamil, Nimodipine, Flunarizine have modest
efficacy as prophylaxis against migraine.

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 ANTIDEPRESSANTS

 Tricyclic antidepressants Amitriptyline, Nortriptyline ,

Imipramine, are used for prevention of migraine.

 They affect the level of serotonin and other brain

chemicals.

 Selective Serotonin Reuptake Inhibitors (SSRIs) and

Serotonin – Norepinephrine Reuptake Inhibitors
(SNRIs) are not proved for migraine.

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 DRUGS USED IN MIGRAINE

Anti-seizure drugs
 Valproate, Topiramate and Gabapentin reduces the
frequency of migraine.
 Lamotrigine may be helpful in migraine with aura.

 Botulinum toxin type A (Botox): The FDA has

approved botulinum toxin type - A for treatment of
chronic migraine headache in adults.

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