IMITREX sumatriptan succinate

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IMITREX(sumatriptan succinate)

• University of North Carolina at Wilmington
• By Lauren Varamo, Sara Waltz, Daniel Tozour,
  Kathryn Smith, Robert Trost, James Svetlovics

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What is a Migraine?

• Blood vessels of the brain expand, due to a
  decrease in the level of serotonin.
• This expansion leads to pressure on neighboring
  nerves resulting in severe pain in the head area.
• Imitrex works by targeting the nerves and blood
  vessels affected by this expansion.

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Imitrex Discovery

• The class of drugs called Triptans came onto the
  market in the early 1990s to assist in migraine
  pain
• Prior to Triptans, believed that migraines caused
  by pressure on nerves from dilated blood vessels.
• Treated with ergotamines that constrict blood
  vessels Cafergot, Wigraine
• Lots of side effects, major health risks severe
  coronary artery disease, peripheral vascular
  disease

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Discovery of Imitrex

• New era in migraine drugs, 1973
• Following up on numerous observations implicating
  more selective agonist, serotonin (potent
  vasoconstrictor pain modulator)
• 1997, GlaxoSmithKline introduced first of new
  serotonin agonists, sumatriptan (Imitrex)

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Structure

• Imitrex (Sumatriptan Succinate)

Imitrex (Sumatriptan Succinate)
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Methods of Administration

• 24 hr. Period
• Oral Tablet (max. 200 mg)
• Injection (max. 12 mg injection/200 mg. oral)
• Nasal Spray (max. 40 mg)
• Imitrex only taken at SIGN of migraine, not
  on regular basis. Will NOT prevent future
  migraines!

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Mechanism of Action

• Exact mechanism of action is not known at this
  time.
• Binding Sites
• -All 5-HT (5 Hydoroxyltryptamine) receptors
• -Also weakly binds to all subtype receptors
• h5-HT1D and h5-HT1B

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Absorption/Distribution/Meta-bolism/Excretion

• Protein binding very low in the blood stream
  (approx. 14-21)
• First pass metabolism-enter blood stream and
  metabolized in liver by the A isoenzyme (MAO-A)
  where it undergoes an oxidative deamination
  pathway into an inactive metabolite.
• 60 renally excreted, other 40 in feces

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Side Effects/Toxicity

• Allergic Reactions (swelling, redness, burning,
  numbness, etc.)
• Long list of less serious side-effects including
  Nausea, Vomiting, Diarrhea, dizziness, drooling,
  etc.
• Serious side-effects including tightness of
  neck/jaw, fainting, seizures, abdominal pain,
  cold sensation in limbs, etc.
• Many, Many, Many medications have serious
  interactions with Imitrex (MAOI,
  Anti-depressants, other migraine medications

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Seritonin Syndrome

• Between 1998 and 2002 27 cases were reported
  where serotonin syndrome was associated with the
  use of triptans and SSRIs.
• Two were life threatening
• Eight were related to incresed doseages

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Serotonin Syndrome cont

• 1,000,000 people over 1998-2001 only 27 cases
• 0.03 have syndrome, 0.002 were life threatening
• Can occur from SSRIs and SNRIs alone
• 1,784 patients on SSRIs were given triptans and
  no neurological events were noted.