Pharm. Management of Headache

Question 1

Pathophysiology of migraine

Answer 1

Current understanding suggests that a primary neuronal dysfunction leads to a sequence of intracranial and extracranial changes that account for migraine symptoms. There is strong evidence to implicate serotonin (5HT) in the pathogenesis of migraine.

2 phases:

1. Cerebral vasoconstriction and ischemia. Serotonin release (5HT) from neurons and platelets (PERIPHERAL MECHANISMS) that acts on 5-HT2 receptors contributes to this phase.
2. Cerebral vasodilation and pain. Trigeminal neurovascular system appears to have a central role in the second phase. Neurons in the trigeminal complex release the vasoactive peptides substance P [SP] and calcitonin gene-related peptide [CGRP] that trigger vasodilation and neuroinflammation of pial and dural vessels (sensory nerve discharge). This in turn stimulates nociceptive fibers of the trigeminal nerve that causes pain.

Question 2

Treatment of migraines

Answer 2

1. NSAIDs and Acetaminophen
2. If not enough, use triptans (sumatriptan)
3. Ergot Alkaloids (Dihydroergotamine)

Question 3

Preventive therapy for migraines

Answer 3

1. Antihypertensive agents (beta-blockers: 1st line, a channels blockers, ACE inhibitors)
2. Antidepressants
3. Anticonvulsants
4. Botox
5. Methysergide (serotonin antagonist)
6. NSAIDs
7. Dietary supplements (Riboflavin, butterbur, feverfew)

Question 4

Preventive therapy for tension headaches

Answer 4

SSRIs

Question 5

Abortive therapy for tension headaches

Answer 5

NSAIDs and muscle relaxants

Question 6

Adverse drug rxns with sumatriptan

Answer 6

Paresthesias, flushing, dizziness, drowsiness, chest tightness

Rarely: coronary vasospasm, angina, MI, arrhythmia, stroke, death

Question 7

Drug-drug interactions with sumatriptan

Answer 7

Additive vasoconstriction with ergot alkaloids

Increased risk of serotonin syndrome** with MAOIs - risk very much less with SNRIs-SSRIs

Question 8

Adverse drug rxns with ergot alkaloids

Answer 8

Nausea / vomiting (give w/antiemetic), diarrhea, cramps, paresthesias

Serious effects: vascular occlusion and gangrene (strict dosage limits)

Mediated via α1 adrenergic vasoconstriction

Question 9

Drug-drug interactions with ergot alkaloids

Answer 9

Severe peripheral ischemia if used with non-selective (β1-β2) beta-blockers