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Migraine Ergot Alkaloids
Module 3 — Ergotamine, Dihydroergotamine, Contraindications, and Drug Interactions
Ergotamine vs. Dihydroergotamine
Ergotamine
Prototype Migraine Ergot
- Serotonin type 1B/1D agonist — meningeal vasoconstriction
- Also: serotonin type 2, alpha-adrenergic, dopamine activity
- Routes: oral, sublingual, rectal (variable absorption)
- Cafergot: ergotamine + caffeine combination
- Second-line to triptans for most patients
Dihydroergotamine
Semi-Synthetic Derivative
- Reduced peripheral vasoconstriction vs. ergotamine
- Less nausea than ergotamine
- Routes: intravenous, intramuscular, intranasal — no oral
- Role: refractory migraine and status migrainosus
- Raskin protocol: repetitive intravenous dosing over days
Contraindications and Rules
Absolute Contraindications
When Not to Use
- Coronary artery disease — coronary vasospasm risk
- Peripheral vascular disease
- Uncontrolled hypertension
- Pregnancy — uterotonic activity
Combination Rule
24-Hour Separation from Triptans
- Ergot + triptan within 24 hours = additive vasospasm risk
- Rule applies in both directions
- Risk: myocardial infarction, stroke
- Medication overuse headache: risk with use ≥10 days/month
Cytochrome P450 3A4 Drug Interaction
Classic Step 1 Interaction
Cytochrome P450 3A4 Inhibitors Raise Ergot Levels
- Macrolides: erythromycin, clarithromycin — contraindicated; azithromycin is safe
- Azole antifungals: itraconazole, ketoconazole — contraindicated
- Protease inhibitors: ritonavir — contraindicated
- Consequence: ergot plasma concentrations rise dramatically → severe ergotism
Step 1 Rules
Ergot + cytochrome P450 3A4 inhibitor = ergotism risk (absolutely contraindicated). Ergot + triptan within 24 hours = additive vasospasm (absolutely contraindicated). Ergot use ≥10 days/month = medication overuse headache. Dihydroergotamine: no oral form; use intravenous/intramuscular/intranasal for refractory migraine.