LiverTox: Clinical and Research Information on Drug-Induced Liver Injury

Migraine headaches are marked by repeated, paroxysmal attacks of moderate-to-severe throbbing, one-sided headaches which (without treatment) last 4 to 72 hours and are usually associated with symptoms of nausea and vomiting. Migraine headaches are typically exacerbated by motion, bright lights and loud noises. Migraines may be associated with focal neurological symptoms referred to as “aura” which are typically visual, but may be sensory or motor. Migraine headaches are common, affecting at least 18% of women and 6.5% of men in the United States. The pattern of paroxysmal headaches typically arises in adolescence or young adulthood and may be life-long. The headaches often interfere with daily activities and can be incapacitating, result in major time loss from work and precipitate multiple physician and emergency room visits. Patients with migraine may also be at increased risk for other vascular complications such as stroke and eclampsia. The cause of migraine headaches is not fully understood, but appears to be related to arteriolar vasodilation and inflammation of the trigeminal nerve endings, perhaps caused by local release of vasoactive peptides. The most convincing candidate mediator of migraines is the calcitonin gene related protein (CGRP), a neuropeptide found throughout the central and peripheral nervous systems which has potent vasodilator and pain-signaling activities. Circulating levels of CGRP are elevated in pateints with migraines, and the efficacy of migraine therapies such as serotonin receptor agonists and ergot alkaloids is associated with lowering of circulating CGRP levels. Antagonists of CGRP have become a focus of migraine headache prevention and therapy. Therapy of migraine headache usually combines preventive treatments with early intervention for acute attacks. Early treatment approaches to migraine have included a number of different classes of medications including nonsteroidal antiinflammatory agents, opiate and nonopiate analgesics, barbiturates, antiemetics, ergot alkaloids, and serotonin receptor agonists. Medications used specifically to treat migraine headaches and discussed here are the ergot alkaloids and the more recently developed serotonin receptor agonists (triptans). The ergot alkaloids have been in use for many years, and currently available forms include ergotamine (Cafergot: year of approval, 1948) and dihydroergotamine (Migranal: 1946). The triptans include sumatriptan (Imitrex: 1997), zolmitriptan (Zomig: 1997), naratriptan (Amerge: 1998), rizatriptan (Maxalt: 1998), almotriptan (Almogran, Axert: 2001), frovatriptan (Frova: 2001), and eletriptan (Relpax: 2002).