Chapter 30

Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.

Chapter 30

Drugs for Headache

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Headache Common symptom Triggered by a variety of stimuli

Stress, fatigue, acute illness, sensitivity to alcohol Mild episodes

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

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, migraine-

specific drugs Prevent attacks from occurring

• Beta blockers, TCAs, and antiepileptic drugs

TCAs = tricyclic antidepressants.

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Migraine Headache I Characteristics

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)

Hormonal component Family history typical Two primary forms

• Migraine with aura Preceded by visual symptoms

• Migraine without aura More common than with aura

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Migraine Headache I Pathophysiology

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• Migraine-specific drugs

Ergot alkaloids, serotonin1B/1D receptor agonists (triptans) Preventing attacks from occurring

• Beta blockers, TCAs, antiepileptic drugs

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Migraine Headache I Nondrug measures

Adequate sleep Exercise Avoiding triggers Once headache begins

• Dark room with ice pack to neck

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Migraine Headache II: Abortive Therapy

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• Teratogenesis• Others

Vertigo, malaise, fatigue, tingling sensations Very bad taste when taken in intranasal form

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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

Preferred drugs for migraine prevention Tricyclic antidepressants Antiepileptic drugs

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