Ergot Derivatives
Ergot derivatives are used to treat migraine headache and enhance uterine contraction post partum. Ergots are produced by the fungus Claviceps purpurea, which may grow on rye and other grains. Natural or synthetic ergot drugs include ergotamine (Cafergot, Ergomar, Gynergen, and Ergostat), methysergide (Sansert), dihydroergotamine (DHE-45), and ergonovine (Ergotrate). Some ergoloid derivatives (dihydroergocornine, dihydroergocristine, and dihydroergocryptine) have been used in combination (Hydergine and Deapril-ST) for the treatment of dementia. Bromocriptine (Parlodel [See Bromocriptine]) and pergolide (Permax) are ergot derivatives with dopamine agonist activity that are used to treat Parkinson disease. Bromocriptine is also used to treat hyperprolactinemic states.
Mechanism of toxicity
Ergot derivatives directly stimulate vasoconstriction and uterine contraction, antagonize alpha-adrenergic and serotonin receptors, and may dilate some blood vessels via a CNS sympatholytic action. The relative contribution of each of these mechanisms to toxicity depends on the particular ergot alkaloid and its dose. Sustained vasoconstriction causes most of the serious toxicity; reduced blood flow causes local tissue hypoxia and ischemic injury, resulting in tissue edema and local thrombosis, worsening ischemia, and causing further injury. At a certain point, reversible vasospasm progresses to irreversible vascular insufficiency and limb gangrene.
Pharmacokinetics (see Table II–61
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