Ergot derivatives are used to treat migraine headache and enhance uterine contraction postpartum. Ergots are produced by the fungus Claviceps purpurea, which may grow on rye and other grains. Natural or synthetic ergot drugs include ergotamine, dihydroergotamine, methysergide, methylergonovine, and ergonovine. Some ergoloid derivatives (dihydroergocornine, dihydroergocristine, and dihydroergocryptine) have been used in combination for the treatment of dementia. Bromocriptine, pergolide, and cabergoline are ergot derivatives with dopamine agonist activity that have been used to treat Parkinson disease. Pergolide has been withdrawn from the U.S. market, but may be available in other countries. Bromocriptine is also used to treat hyperprolactinemic states.

1. Ergot derivatives have very complex pharmacologic properties, including varying degrees of central and peripheral agonist, antagonist or mixed activity at serotonergic, dopaminergic, and alpha-adrenergic receptors. Ergots directly stimulate vasoconstriction and uterine contraction and may indirectly dilate some vessels via 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 and worsening ischemia, and leading to further injury. At a certain point, reversible vasospasm progresses to irreversible vascular insufficiency and limb gangrene.
2. Pharmacokinetics. Ergot alkaloids are extensively metabolized and highly tissue-bound, the latter characteristic accounting for protracted clinical ergot poisoning after the drug is stopped. Most of the ergots undergo hepatic metabolism. Ergotism has occurred in people taking HIV protease inhibitors in combination with ergots for migraine, presumably owing to inhibition of ergot metabolism via CYP3A4.

Death has been reported in a 14-month-old child after acute ingestion of 12 mg of ergotamine. However, most cases of severe poisoning occur with overmedication for migraine headaches rather than acute single overdoses. Daily doses of 10 mg or more of ergotamine are usually associated with toxicity. There are many case reports of vasospastic complications with normal therapeutic dosing. Toxicity can also occur with chronic ingestion of grain contaminated with C. purpurea, which may occur in some developing countries where ergot levels in food are poorly regulated.

1. Ergotamine and related agents. Mild intoxication causes nausea, vomiting and abdominal cramping. Serious poisoning results in vasoconstriction that may involve many parts of the body. Owing to persistence of ergots in tissues, vasospasm may continue for up to 10-14 days.
   1. Involvement of the extremities causes paresthesias, burning pain, pallor, coolness, and loss of peripheral pulses in the hands and feet; gangrene may ensue. Historically, this syndrome was called “St. Anthony's fire” when it occurred after ingestion of contaminated grain.
   2. Other complications of vasospasm include coronary ischemia and myocardial infarction, abdominal angina and bowel infarction, renal infarction and failure, visual disturbances and blindness, and stroke. Psychosis, seizures, and coma occur rarely.
   3. Central nervous system toxicity can include headache, confusion, psychosis, hallucination, and seizures.
   4. Iatrogenic neonatal ergot poisoning has occurred when methylergonovine meant for the mother after delivery was administered mistakenly to the baby. Manifestations include respiratory failure, apnea, cyanosis, hypotension, peripheral ischemia, oliguria, and seizures.
2. Bromocriptine intoxication may present with hallucinations, paranoid behavior, hypertension, and tachycardia.
3. Chronic use of methysergide, pergolide, and cabergoline have been associated with cardiac, pulmonary, and retroperitoneal fibrosis.

Is based on a history of ergot use and clinical findings.

1. Specific levels. Ergotamine levels are not widely available, and blood concentrations do not correlate well with toxicity.
2. Other useful laboratory studies include CBC, electrolytes, BUN, creatinine, cardiac troponin, and ECG. Arteriography of the affected vascular bed is indicated occasionally.

1. Emergency and supportive measures
   1. Maintain an open airway and assist ventilation if necessary.
   2. Treat coma and convulsions (p 23) if they occur.
   3. Immediately discontinue ergot treatment. Hydration and analgesia should be provided. Hospitalize patients with vasospastic symptoms and treat promptly to prevent complications.
2. Specific drugs and antidotes
   1. Peripheral ischemia requires prompt vasodilator therapy and anticoagulation to prevent local thrombosis.
      1. Vaodilators. In mild cases, oral immediate release nifedipine may be administered. In more severe cases parenteral vasodilators should be used. Options include IV nitroprusside (p 564), IV phentolamine, IV nicardipine, or IV clevidipine. The infusion rate should be increased progressively until ischemia is relieved or systemic hypotension occurs. Intra-arterial nitroprusside infusion is occasionally required. Case reports have also noted successful use of infusions of prostacyclin, prostaglandin E1, and oral sildenafil.
      2. Anticoagulation. Administer heparin, 5,000 units IV followed by 1,000 units/h (in adults), with adjustments in the infusion rate to maintain the activated coagulation time (ACT) or the activated partial thromboplastin time (aPTT) at approximately 2 times the baseline.
   2. Coronary spasm. Administer nitroglycerin, 0.15-0.6 mg sublingually or 5-20 mcg/min IV. Intracoronary artery nitroglycerin may be required if there is no response to IV infusion. Also consider using a calcium antagonist.
   3. Hallucinations or seizures should be treated with benzodiazepines.
3. Decontamination after acute ingestion. Administer activated charcoal orally if conditions are appropriate (see Table I-37). Gastric lavage is not necessary after small-to-moderate ingestions if activated charcoal can be given promptly.
4. Enhanced elimination. Dialysis and hemoperfusion are not effective. Repeat-dose charcoal has not been studied, but because of extensive tissue distribution of ergots, it is not likely to be useful.