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Anti-Migraine Drugs

Anti-Migraine Drugs. Brian Lich April 3 rd , 2007. Overview. Migraines: What are they? Symptoms? Causes? History: What was done? Today: How are migraines currently treated? Specific Drugs and their mode of action Future: What are some drug “prospects”?. Migraines.

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Anti-Migraine Drugs

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  1. Anti-Migraine Drugs Brian Lich April 3rd, 2007

  2. Overview • Migraines: What are they? Symptoms? Causes? • History: What was done? • Today: How are migraines currently treated? • Specific Drugs and their mode of action • Future: What are some drug “prospects”?

  3. Migraines • Migraine: a neurological disease characterized by attacks of headache, photophobia, phonophobia, and nausea. • 3 times more common in women than men • Up to 28 million people in the US are affected

  4. The 4 phases of a migraine • Prodrome • Occurs hours to days before migraine without headache • Aura • Neurological phenomena such as disturbance of vision just before headache • Pain phase • Headache on one side of head with nausea, photophobia and other classic migraine symptoms • Postdrome • Exhaustion, irritability, depression

  5. Headache vs. Migraine • Headache • Pain usually dispersed throughout head • Migraine • Pain concentrated on one side of head

  6. What causes these symptoms? • Exact mechanism still not known • Not initiated by blood vessel problems • This is secondary • Cortical spreading depression • Inflammatory mediators irritate cranial nerves, especially the trigeminal nerve

  7. Where does the headache come from? • When a headache occurs, serotonin and magnesium levels drop • Trigeminal nerve releases neuropeptides • Neuropeptides travel to outer covering of the brain and cause dilation and inflammation of meningeal blood vessels • Dura and dura vessels disrupted but brain structure remains intact • No increased risk of a brain tumor

  8. Causes • Mechanism still debated • Common triggers • Hormonal: Estrogen and Progesterone • Foods: alcohol, chocolate, etc. • Stress, physical activity, sleep • Environmental stimulus: sight, smells • medications

  9. Treatments of the Past • Migraines have been have a medical history of 9000 years • First mode of treatment: trepanation • Galen of Pergamum was an ancient Greek physician in the 2nd century AD • Used the term “hemicrania” for which he thought the brain and stomach were connected • “Migraine” evolved from this term

  10. Treatments of the Past… • Up through medieval ages, treated with a hot iron to the head, blood letting • Still very much misunderstood as in the case of other neurological disorders • Today, some physicians still hesitant to prescribe specific anti-migraine drugs

  11. Treatments of today • Non-specific • Aspirin, NSAIDs • Ergots • 5-hydroxytryptamine (5-HT) agonists • Sumatriptan (imitrex) • Zolmitriptan • Naratriptan • Rizatriptan

  12. Aspirin • First choice drug to treat mild to moderate migraine attacks • As we know, aspirin inhibits COX-1, stopping prostaglandin synthesis from arachidonic acid • *aspirin also shows inhibitory effects on how the trigeminal nerve processes inputs (reduces pain)

  13. Ergotamine • Vasoconstrictor • Therefore cannot be administered to patients with coronary diseases • Inhibits release of calcitonin gene-related peptide (CGRP) • Interact with many different neurotransmitter receptors not specific

  14. Ergotamine mode of action Inhibits release of CGRP CGRP-receptor antagonists are being explored today

  15. 5-hydroxytryptamine (5-HT) agonists • A group of drugs known as triptans bind the serotonin 5-HT1B receptors in the walls of blood vessels • Leads to constriction of arteries, particularly at cerebral and dura arteries • Triptans also inhibit inflammation of vessels of the dura matter that are stimulated by the trigeminal ganglion • Do this by acting as a 5-HT1D receptor agonist

  16. 5-HT receptor

  17. Sumatriptan (imitrex) Sumatriptan Serotonin Vs. First triptan on the market and still very popular Cannot cross the intact BBB because it is too polar  requires much higher doses to be effective

  18. New 5-HT agonists • All designed to penetrate BBB • Can better bind 5-HT receptors in brain as agonist to stimulate constriction • BUT, also should have the least possible vasoconstrictive effects on coronary arteries

  19. Examples of new 5-HT agonists Naratriptan Serotonin Rizatriptan Eletriptan Zolmitriptan

  20. Migraine Drugs of the Future • Botox • Immediate relief and migraine prophylaxis/prevention • Administration of magnesium • Patent foramen ovale surgery • Evidence that when hole between upper chambers of the heart is patched, migraines are relieved

  21. Thank you!

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