Chapter 30
Drugs for Headache
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Headache
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
Common symptom
Triggered by a variety of stimuli


Mild episodes
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
Stress, fatigue, acute illness, sensitivity to alcohol
Relieved by over-the-counter drugs (OTCs) (e.g.,
aspirin, acetaminophen)
Severe headaches

Migraine, cluster, tension-type
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Medication Overuse Headache
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Headaches

Identifiable underlying causes
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
Severe hypertension, hyperthyroidism, tumor,
infection, and disorders of the eye, nose, sinuses,
and throat
No identifiable cause


Migraine
Cluster
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Headaches





Migraine headache I: characteristics and
overview of treatment
Migraine headache II: abortive therapy
Migraine headache III: preventive therapy
Cluster headaches
Tension-type headache
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Headaches


Overview of treatment
Drugs used in two ways
 Abort an ongoing attack
• Aspirin-like drugs, opioid analgesics, migrainespecific drugs
 Prevent
attacks from occurring
• Beta blockers, TCAs, and antiepileptic drugs
TCAs = tricyclic antidepressants.
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Migraine Headache I

Characteristics
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


Throbbing head pain of moderate to severe
intensity
Nausea and vomiting
Sensitivity to light and sound
Highly debilitating
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Migraine Headache I

Characteristics (cont’d)
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

Hormonal component
Family history typical
Two primary forms
• Migraine with aura

Preceded by visual symptoms

More common than with aura
• Migraine without aura
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Migraine Headache I

Pathophysiology
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

Neurovascular disorder that involves dilation and
inflammation of intracranial blood vessels
Vasodilation leads to pain
Neurons of the trigeminal vascular system
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Migraine Headache I

Overview of treatment

Aborting an ongoing attack
• Nonspecific analgesics

Aspirin-like drugs and opioid analgesics

Ergot alkaloids, serotonin1B/1D receptor agonists (triptans)
• Migraine-specific drugs

Preventing attacks from occurring
• Beta blockers, TCAs, antiepileptic drugs
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Migraine Headache I

Nondrug measures
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Adequate sleep
Exercise
Avoiding triggers
Once headache begins
• Dark room with ice pack to neck
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Migraine Headache II:
Abortive Therapy
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

Objective: to eliminate headache pain and
suppress associated nausea/vomiting
Earliest treatment possible
Route of administration



Oral not effective owing to GI distress
Injection, inhalation, rectal suppository may be
more effective
Antiemetics
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Selection of Drugs

Mild to moderate headache

Aspirin-like drugs
• Aspirin, acetaminophen, ibuprofen, and other aspirin-like
analgesics

Moderate to severe



Migraine-specific drug
Opioid analgesics
Antiemetics
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Ergot Alkaloids

Ergotamine

Mechanism of antimigraine action
• Exact mechanism unknown
 Therapeutic uses
• Drug of choice to stop an ongoing migraine
 Pharmacokinetics
• PO, sublingual, rectal, or inhalation
 Adverse effects
• Nausea/vomiting, weakness in the legs, myalgia,
numbness and tingling in fingers or toes, angina-like
pain, tachycardia or bradycardia
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Ergot Alkaloids

Ergotamine (cont’d)

Overdose
• Ergotism
 Drug interactions
• Triptans, CYP3A4 inhibitors
 Physical dependence
• Risk of regular daily use
 Contraindications
• Hepatic or renal impairment
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Ergot Alkaloids

Dihydroergotamine

Therapeutic uses
• Drug of choice for terminating migraine and cluster
headaches


Pharmacologic effects
• Similar to ergotamine
Pharmacokinetics
• Only parenteral or nasal spray administration—not oral
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Ergot Alkaloids

Dihydroergotamine (cont’d)


Drug interactions
• CYP3A4 inhibitors, serotonin agonist
Contraindications
• Patients with coronary artery disease (CAD), peripheral
vascular disease (PVD), sepsis, pregnancy, hepatic or
renal impairment
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Serotonin1B/1D Receptor Agonists

Sumatriptan (Imitrex)

Mechanism of action
• Binds to receptors on intracranial blood vessels and
causes vasoconstriction
• Diminishes perivascular inflammation

Therapeutic use
• Aborting an ongoing migraine attack to relieve headache
and associated symptoms

Pharmacokinetics
• Oral or intranasal administration
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Serotonin1B/1D Receptor Agonists

Sumatriptan (cont’d)

Adverse effects
• Chest symptoms

Transient “heavy arms” or “chest pressure” experienced by
50% of users
• Coronary vasospasm

Rare angina secondary to vasospasm

Vertigo, malaise, fatigue, tingling sensations
Very bad taste when taken in intranasal form
• Teratogenesis
• Others

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Serotonin1B/1D Receptor Agonists

Drug interactions


Ergot alkaloids, sumatriptan, other triptans (all
cause vasoconstriction)
Preparations, dosage, and administration


Oral
Nasal spray
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Serotonin1B/1D Receptor Agonists

Other serotonin1B/1D receptor agonists






Zolmitriptan
Naratriptan
Rizatriptan
Almotriptan
Frovatriptan
Eletriptan
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Migraine Headache III

Beta blockers



Tricyclic antidepressants
Antiepileptic drugs



Preferred drugs for migraine prevention
Divalproex
Topiramate
Estrogens (for menstrual migraine)
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Migraine Headache III

Other drugs for prophylaxis



Calcium channel blockers
Candesartan, an angiotensin II receptor blocker
(ARB)
Supplements
• Riboflavin
• Coenzyme Q-10
• Feverfew
• Butterbur
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Cluster Headaches

Characteristics






Occur in a series or “cluster” of attacks
Each attack lasts 15 minutes to 2 hours
Severe, throbbing, unilateral pain near the eye
Lacrimation, conjunctival redness, nasal
congestion, rhinorrhea, ptosis, miosis on the same
side of the headache
1–2 attacks every day for 2–3 months
An attack-free interval of months to years
separates clusters
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Cluster Headaches

Treatment

Primary therapy directed at prophylaxis
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Tension-Type Headache

Characteristics





Most common form of headache
Moderate, nonthrobbing pain
Usually located in a “head band” distribution
May be episodic or chronic
Treatment


Nonopioid analgesics
Patient teaching on how to manage stress
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