Dihydroergotamine
Synonym :
DHE
Mechanism :
The therapeutic activity of dihydroergotamine in migraine is attributed to the agonist effect at 5-HT1D receptors. Two current theories have been proposed, one theory suggests that activation of 5-HT1D receptors located on intracranial blood vessels, including those on arterio-venous anastomoses, leads to vasoconstriction, which correlates with the relief of migraine headache. The alternative hypothesis suggests that activation of 5-HT1D receptors on sensory nerve endings of the trigeminal system results in the inhibition of pro-inflammatory neuropeptide release.
Indication :
- Acute migraine headaches with or without aura
- Acute cluster headache
Contraindications :
Dihydroergotamine should not be given to patients with ischemic heart disease or to patients who have clinical symptoms or findings consistent with coronary artery vasospasm, or to patients with uncontrolled hypertension. Ergotamine-containing or ergot-type medications or methysergide should not be used within 24 hours of each other. Should not be administered to patients with hemiplegic or basilar migraine.
Contraindicated in patients with known peripheral arterial disease, sepsis, following vascular surgery and severely impaired hepatic or renal function. Dihydroergotamine possesses oxytocic properties and therefore, should not be administered during pregnancy. Dihydroergotamine mesylate is contraindicated in patients who have previously shown hypersensitivity to ergot alkaloids.
Dosing :
Dosing should be adjusted and may require some individualization: Dose (Mg) = (adult dose in mg) × (patient weight in kg) × (0.014) mg
Adult dosing:
Intermittent IV infusion: Day 1: First dose: 0.5 mg in 100 mL of normal saline over 1 hour If well tolerated, escalate dosing as follows: Second dose, 8 hours later: 0.75 mg in 250 mL of normal saline over 1 hour Day 2-5: Third and subsequent doses: 1 mg
Adverse Effect :
Coronary artery vasospasm, transient myocardial ischemia, myocardial infarction, ventricular tachycardia, and ventricular fibrillation.
Interaction :
Vasoconstrictors: Combination may cause synergistic elevation of blood pressure.
Sumatriptan: Sumatriptan has been reported to cause coronary artery vasospasm, and its effect could be additive with dihydroergotamine mesylate, should not be taken within 24 hours of each other.
Beta Blockers: Propranolol may potentiate the vasoconstrictive action of ergotamine by blocking the vasodilating property of epinephrine.
Nicotine: Nicotine may provoke vasoconstriction in some patients, predisposing to a greater ischemic response to ergot therapy.
Macrolide Antibiotics (e. g. erythromycin and troleandomycin): Agents of the ergot alkaloid class, have been shown to interact with antibiotics of the macrolide class, resulting in increased plasma levels of unchanged alkaloids and peripheral vasoconstriction. Vasospastic reactions have been reported with therapeutic doses of ergotamine-containing drugs when co-administered with these antibiotics.
SSRI's: Weakness hyperreflexia, and incoordination have been reported rarely when 5-HT1 agonists have been co-administered with SSRI's (e. g. fluoxetine, fluvoxamine, paroxetine, sertraline).
Hepatic Dose :
Avoid use due to risk of ergot toxicity.