Chapter 30

1. Chapter 30 Drugs for Headache

2. 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

3. Medication Overuse Headache

4. Headaches • Identifiable underlying causes • Severe hypertension, hyperthyroidism, tumor, infection, and disorders of the eye, nose, sinuses, and throat • No identifiable cause • Migraine • Cluster

5. Headaches • Migraine headache I: characteristics and overview of treatment • Migraine headache II: abortive therapy • Migraine headache III: preventive therapy • Cluster headaches • Tension-type headache

6. 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.

7. Migraine Headache I • Characteristics • Throbbing head pain of moderate to severe intensity • Nausea and vomiting • Sensitivity to light and sound • Highly debilitating

8. 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

9. 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

10. 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

11. Migraine Headache I • Nondrug measures • Adequate sleep • Exercise • Avoiding triggers • Once headache begins • Dark room with ice pack to neck

12. 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

13. 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

14. 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

15. Ergot Alkaloids • Ergotamine (cont’d) • Overdose • Ergotism • Drug interactions • Triptans, CYP3A4 inhibitors • Physical dependence • Risk of regular daily use • Contraindications • Hepatic or renal impairment

16. 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

17. 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

18. 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

19. 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

20. Serotonin1B/1D Receptor Agonists • Drug interactions • Ergot alkaloids, sumatriptan, other triptans (all cause vasoconstriction) • Preparations, dosage, and administration • Oral • Nasal spray

21. Serotonin1B/1D Receptor Agonists • Other serotonin1B/1D receptor agonists • Zolmitriptan • Naratriptan • Rizatriptan • Almotriptan • Frovatriptan • Eletriptan

22. Migraine Headache III • Beta blockers • Preferred drugs for migraine prevention • Tricyclic antidepressants • Antiepileptic drugs • Divalproex • Topiramate • Estrogens (for menstrual migraine)

23. Migraine Headache III • Other drugs for prophylaxis • Calcium channel blockers • Candesartan, an angiotensin II receptor blocker (ARB) • Supplements • Riboflavin • Coenzyme Q-10 • Feverfew • Butterbur

24. 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

25. Cluster Headaches • Treatment • Primary therapy directed at prophylaxis

26. 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