Ergotamine preparations

Ergotamine preparations

Ergotamine and its derivatives may be used as abortive or sympto-matic therapy for migraine.

Some common preparations used for migraine include:

·                 ergotamine, available in sublingual and oral tablets and supposi-tories (combined with caffeine)

·                 dihydroergotamine, available in injectable and intranasal forms.

Pharmacokinetics

Ergotamine is incompletely absorbed from the GI tract. The in-tranasal form of dihydroergotamine is rapidly absorbed. Peak plasma concentration, following subcutaneous injection, is within 45 minutes, and 90% of the dose is plasma protein-bound. Ergota-mine is metabolized in the liver, and 90% of the metabolites are ex-creted in bile; traces of unchanged drug are excreted in urine.

Pharmacodynamics

Ergotamine-derivative antimigraine effects are believed to be due to blockade of neurogenic inflammation. They also act as partial agonists or antagonists at serotonin, dopaminergic, and alpha-adrenergic receptors depending on their site. Ergotamine prepara-tions often need to be prescribed with antiemetic preparations when used for migraine.

Dihydroergotamine, a hydrogenated form of ergotamine, dif-fers mainly in degree of activity. It has less vasoconstrictive action than ergotamine and much less emetic potential.

Pharmacotherapeutics

Ergotamine preparations are used to prevent or treat vascular headaches, such as migraine, migraine variant, and cluster headaches. Dihydroergotamine is used when rapid control of mi-graine is desired or when other routes are undesirable.

Drug interactions

Propranolol and other beta-adrenergic blocking drugs block the natural pathway for vasodilation in patients receiving ergotamine preparations, resulting in excessive vasoconstriction and cold ex-tremities.

Steady, now…

·                 There may be an increased risk of weakness, hyperflexion, and incoordination when using ergotamine preparations with SSRIs.

·                 Sumatriptan may cause an additive effect, increasing the risk of coronary vasospasm. Don’t give any ergotamine prepa-rations and triptans within 24 hours of each other.

·                 Drugs that inhibit the CYP3A4 enzyme (such as ery-thromycin, clarithromycin, ritonavir, nelfinavir, indinavir, and azole-derivative antifungal agents) may alter the metabolism of ergotamine, resulting in increased serum concentrations of er-gotamine. This increases the risk of vasospasm and cerebral or peripheral ischemia. These drugs shouldn’t be used together.

·                 Vasoconstrictors may cause an additive effect when given with ergotamine preparations, increasing the risk of high blood pres-sure. (See Adverse reactions to ergotamine derivatives.)