1. Drugs for Headaches 1

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 2

3. Medication Overuse Headache3

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

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 5

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. 6

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

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 8

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 9

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 10

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

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 12

13. Selection of Drugs Mild to moderate headache Moderate to severe
Aspirin-like drugs
Aspirin, acetaminophen, ibuprofen, and other aspirin-like analgesics
Moderate to severe
Migraine-specific drug
Opioid analgesics
Antiemetics 13

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 14

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

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 16

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 17

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 18

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 19

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

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

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

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 23

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 24

25. Cluster Headaches
Treatment
Primary therapy directed at prophylaxis 25

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 26