Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Chapter 30 Drugs for Headache

2Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 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

3Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Medication Overuse Headache

4Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Headaches  Identifiable underlying causes  Severe hypertension, hyperthyroidism, tumor, infection, and disorders of the eye, nose, sinuses, and throat  No identifiable cause  Migraine  Cluster

5Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Headaches  Migraine headache I: characteristics and overview of treatment  Migraine headache II: abortive therapy  Migraine headache III: preventive therapy  Cluster headaches  Tension-type headache

6Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Headaches  Overview of treatment  Drugs used in two ways  Abort an ongoing attack Aspirin-like drugs, opioid analgesics, migraine- specific drugs Aspirin-like drugs, opioid analgesics, migraine- specific drugs  Prevent attacks from occurring Beta blockers, TCAs, and antiepileptic drugs Beta blockers, TCAs, and antiepileptic drugs TCAs = tricyclic antidepressants.

7Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Migraine Headache I  Characteristics  Throbbing head pain of moderate to severe intensity  Nausea and vomiting  Sensitivity to light and sound  Highly debilitating

8Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Migraine Headache I  Characteristics (cont’d)  Hormonal component  Family history typical  Two primary forms Migraine with aura Migraine with aura  Preceded by visual symptoms Migraine without aura Migraine without aura  More common than with aura

9Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 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

10Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Migraine Headache I  Overview of treatment  Aborting an ongoing attack Nonspecific analgesics Nonspecific analgesics  Aspirin-like drugs and opioid analgesics Migraine-specific drugs Migraine-specific drugs  Ergot alkaloids, serotonin 1B/1D receptor agonists (triptans)  Preventing attacks from occurring Beta blockers, TCAs, antiepileptic drugs Beta blockers, TCAs, antiepileptic drugs

11Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Migraine Headache I  Nondrug measures  Adequate sleep  Exercise  Avoiding triggers  Once headache begins Dark room with ice pack to neck Dark room with ice pack to neck

12Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 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

13Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Selection of Drugs  Mild to moderate headache  Aspirin-like drugs Aspirin, acetaminophen, ibuprofen, and other aspirin-like analgesics Aspirin, acetaminophen, ibuprofen, and other aspirin-like analgesics  Moderate to severe  Migraine-specific drug  Opioid analgesics  Antiemetics

14Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Ergot Alkaloids  Ergotamine  Mechanism of antimigraine action Exact mechanism unknown Exact mechanism unknown  Therapeutic uses Drug of choice to stop an ongoing migraine Drug of choice to stop an ongoing migraine  Pharmacokinetics PO, sublingual, rectal, or inhalation 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 Nausea/vomiting, weakness in the legs, myalgia, numbness and tingling in fingers or toes, angina-like pain, tachycardia or bradycardia

15Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Ergot Alkaloids  Ergotamine (cont’d)  Overdose Ergotism Ergotism  Drug interactions Triptans, CYP3A4 inhibitors Triptans, CYP3A4 inhibitors  Physical dependence Risk of regular daily use Risk of regular daily use  Contraindications Hepatic or renal impairment Hepatic or renal impairment

16Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Ergot Alkaloids  Dihydroergotamine  Therapeutic uses Drug of choice for terminating migraine and cluster headaches Drug of choice for terminating migraine and cluster headaches  Pharmacologic effects Similar to ergotamine Similar to ergotamine  Pharmacokinetics Only parenteral or nasal spray administration—not oral Only parenteral or nasal spray administration—not oral

17Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Ergot Alkaloids  Dihydroergotamine (cont’d)  Drug interactions CYP3A4 inhibitors, serotonin agonist CYP3A4 inhibitors, serotonin agonist  Contraindications Patients with coronary artery disease (CAD), peripheral vascular disease (PVD), sepsis, pregnancy, hepatic or renal impairment Patients with coronary artery disease (CAD), peripheral vascular disease (PVD), sepsis, pregnancy, hepatic or renal impairment

18Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Serotonin 1B/1D Receptor Agonists  Sumatriptan (Imitrex)  Mechanism of action Binds to receptors on intracranial blood vessels and causes vasoconstriction Binds to receptors on intracranial blood vessels and causes vasoconstriction Diminishes perivascular inflammation Diminishes perivascular inflammation  Therapeutic use Aborting an ongoing migraine attack to relieve headache and associated symptoms Aborting an ongoing migraine attack to relieve headache and associated symptoms  Pharmacokinetics Oral or intranasal administration Oral or intranasal administration

19Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Serotonin 1B/1D Receptor Agonists  Sumatriptan (cont’d)  Adverse effects Chest symptoms Chest symptoms  Transient “heavy arms” or “chest pressure” experienced by 50% of users Coronary vasospasm Coronary vasospasm  Rare angina secondary to vasospasm Teratogenesis Teratogenesis Others Others  Vertigo, malaise, fatigue, tingling sensations  Very bad taste when taken in intranasal form

20Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Serotonin 1B/1D Receptor Agonists  Drug interactions  Ergot alkaloids, sumatriptan, other triptans (all cause vasoconstriction)  Preparations, dosage, and administration  Oral  Nasal spray

21Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Serotonin 1B/1D Receptor Agonists  Other serotonin 1B/1D receptor agonists  Zolmitriptan  Naratriptan  Rizatriptan  Almotriptan  Frovatriptan  Eletriptan

22Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Migraine Headache III  Beta blockers  Preferred drugs for migraine prevention  Tricyclic antidepressants  Antiepileptic drugs  Divalproex  Topiramate  Estrogens (for menstrual migraine)

23Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Migraine Headache III  Other drugs for prophylaxis  Calcium channel blockers  Candesartan, an angiotensin II receptor blocker (ARB)  Supplements Riboflavin Riboflavin Coenzyme Q-10 Coenzyme Q-10 Feverfew Feverfew Butterbur Butterbur

24Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 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

25Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. Cluster Headaches  Treatment  Primary therapy directed at prophylaxis

26Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 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