St. Anthony’s Fire

1. St. Anthony’s Fire

2. Introduction • Caused by ergot • A filamentous fungus • Genus Claviceps • Parasitic • Found in grains • corn, wheat, barley, oats, rice, and rye • Spread via spores • Transported by wind, rain, insects and other animals, or by plant-to-plant contact

3. Introduction • Infection of plants can be easily overlooked • Mimics the shape of grains • Fungal form is the most dangerous • Causes ergotism • Infection usually follows oral consumption of contaminated food ie/ rye bread

4. Overview • History • Signs & Symptoms • Mechanism of Action • Drug Interactions • Treatment • Therapeutic Uses • LSD

5. History • Eleusinian Mysteries • Religious cult between 1500BC and 396AD • Cult of Demeter and Persephone promising pleasant afterlife • Drank ritual drink kykeon before experienceing visions and hallucinations • Kykeon likely contained ergotized barley

6. Tollund Man • Body found in Danish peat bog, from 400BC • Rope around neck, likely drowned as ritual sacrifice

7. Signs and Symptoms • Ergotism can be caused by • Acute ingestion of large amounts of fungus • Chronic ingestion, usually via contaminated food • 2 main categories of symptoms • Gangrenous • Convulsive

8. Gangrenous Symptoms • Dry gangrene caused by tissue necrosis • Fingers and toes are affected first • Followed by arms and legs • Infection may result and can lead to death • Amputation is often the only solution • Happens in livestock as well as in humans

9. Convulsive Symptoms • Includes tingling sensation in the fingers, tinnitus, dizziness, hallucinations, seizures, nausea and vomiting • Mental disturbances such as mania, psychoses and delirium may also be present

10. Kinetics • Many compounds; absorbed to varying degrees from GI tract • Absorption increased in the presence of caffeine (ergotamine) • Extensively metabolized by CYP450 • Cinx in liver failure • Certain drugs inhibit metabolism • Protease inhibitors • Macrolide antibiotics

11. Mechanism of Action • Ergot compounds are structurally similar to the biogenic amines • Dopamine • Serotonin (tryptophan) • Norepinephrine • Serotonergic system particularly affected • Accounts for many of the convulsive symptoms • Similar to symptoms of schizophrenia and epilepsy

12. Mechanism of Action • N/V/D • stimulated serotonin receptors of the GI tract and emetic centres of the brain • LSD • a weak partial agonist at 5HT-2 receptors in the brain • Results in many of the convulsive symptoms

13. Mechanism of Action • All ergot compounds exhibit some vasospastic properties • Effects on serotonin and alpha adrenergic receptors in blood vessels • St. Anthony’s Fire • Body feels extremely warm due to constriction of peripheral vessels

14. Mechanism of Action • Results in myocardial or peripheral ischemia • Gangrene, infection, amputation, death • Cinx in CAD, PAD, uncontrolled HTN • Uterine smooth muscle is also affected by serotonergic and alpha adrenergic effects • Contractions may lead to miscarriage or preterm birth

15. Treatment • 16th and 17th century folk remedies • “green ointment of herbs,  earthworms stamped in vinegar, swan or goose dung stamped with the white or yolk of the egg, or doves dung in salad oil” • Later remedies • “British Oil” originally containing bitumen, • later preparations with oil of turpentine, oil of rosemary and Barbados tar

16. Treatment • Modern-Day Treatment • Early detection and immediate discontinuation of exposure vital • Severe ischemia may be irreversible • If overdose is detected early • Activated charcoal • Gastric lavage if patient is conscious

17. Treatment • Treatment of hallucinations • Stopping exposure to toxin usually effective • Intracranial injection of combination serotonin and cholinergic drugs successful treatment in mice

18. Treatment • Treatment for ischemia • Vasodilators • Nitroprusside, nifedipine, captopril, prostaglandins • Anticoagulants • Dextrin, heparin • In extreme cases of ischemia • Regional sympathectomy • Hyperbaric oxygen chamber • Hydrostatic dilation with balloon catheters

19. Medicinal Uses • Bromocriptine • Stimulates D2 receptors in the brain • Treatment for Parkinson’s • female infertility, abnormal lactation, amenorrhea, hypogonadism, and acromegaly • D2 stimulation • Effective in cocaine withdrawal • Opiate weaning?

20. Medicinal Uses • Pergolide • Anti-Parkinson • 1000x stronger than bromocriptine • Inhibits prolactin • Effects on leutinizing and growth hormone

21. Medicinal Uses • Methysergide • Prophylactic migraine treatment • Activation of 5HT-1D receptors in cranial blood vessels • vasoconstriction • Linked to retroperitoneal fibrosis

22. Medicinal Uses • Ergotamine • Intermittent treatment of migraines • Similar MOA as Methysergide • Cinx in pregnant women • Migraine treatments are non-selective • Overdose or drug interaction may result in ergotism • Triptans are a safer new alternative for migraine treatment

23. Medicinal Uses • Methylergonovine • Used after delivery • Initiates strong contractions of uterine smooth muscle • Contract the uterus, prevent hemorrhage, promote placental passage

24. LSD • Synthesized by Albert Hoffman in 1938 • Accidentally dosed himself • Had the first ‘acid trip’ • Hallucinations, synesthesias, emotionality, body distortions • Used as a psychoanalytic drug • Was thought to elicit repressed memories • Given to alcoholics as part of counselling process

25. LSD • Believed to be helpful in treating schizophrenia • Tried to map out a ‘model psychoses’ using animals • Later realized that schizophrenia and acid trips are very different • Therapeutic use discontinued in the ’60s

26. LSD • CIA • Attempted to use it for mind control • Cold War, Russian spies • Tested it on unsuspecting civilian and military ‘volunteers’ • Caused mental trauma and suicides in subjects • No real use was found for it

27. LSD • Eventually became accessible to the public • Counterculture committed to social change and cultural liberation • Timothy Leary’s League of Spiritual Discovery was a church in the ’70s based on LSD use • Widespread stories of bad trips and flashbacks decreased its use • Legislation was imposed prohibiting LSD

28. LSD • Today it is part of the ‘party drug’ scene • Along with ecstasy and mushrooms

29. References • BAADER, W., HERMAN, C., JOHANSEN, K. (Date?). St. Anthony’s Fire: successful reversal of ergotamine induced peripheral vasospasm by hydrostatic dilation. Annals of Vascular Surgery. 4(6): 597-9. • BROWN, P.S., (1976). Medicines advertised in eighteenth-century Bath newspapers. Med Hist. 20(2): 152-168 • CAPORAEL, L. (1976). Ergotism: the Satan loosed in Salem? Science,192, 21-6. • EDWARDS, R.J., FULDE, G.W., MCGRATH, M.A. (1991). Successful limb salvage with prostaglandin infusion: a review of ergotamine toxicity. Medical Journal of Australia. 155, 825-7 • MATOSSIAN, M. (1989). Poisons of the Past: Molds, Epidemics, and History. New Haven: Yale University Press. • MECHEM, C. (2007). Antipsychotics and LSD lowering of seizure potential, sypathomimetics. http://www.emedicine.com/emerg/topic911.htm • MERRICK, J., GUFLER, K., JACOBSEN, E. (1978). Ergotism treated with hyperbaric oxygen and continuous epideral analgesia. Acta Anaesthesiologica Scandinavica. 67: 87-90 • NAZ, I., SOPHIE, Z., (2006) Acute limb ischemia due to ergotism. Journal of the College of Physicians and Surgeons. 16(8): 553-5. • PANACCIONE, D., COYLE, C. (2005). Abundant respirable ergot alkaloids from the common airborne fungus Aspergillus fumigatus. Applied and Environmental Microbiology, 71, 3106-11. • ROBERTS, T., HRUBY, P. (2001). Religion and Psychoactive Sacraments: • An Entheogen Chrestomathy. Council on Spiritual Practices. • http://www.csp.org/chrestomathy/ergot_and.html • SCHIFF, P. (2006). Ergot and its alkaloids. American Journal of Pharmaceutical Education, 70. • SCHMIDT, R., ERASMI, H., WALTER, M., WOLF, M., GROSS-FENGELS, W. (1992). Ergotism and ischemia of the limbs. Annales de Cardiologie et d’Angeiologie., 41, 489-95. • SOLOGUK, S. (2005). Diseases Can Bewitch Durum Millers. Milling Journal. Second Quarter 2005, 44-45. • STANGE, K., POHLMEIER, H., LUBBESMEYER, A., GUMBINGER, G., SCHMITZ, W., BAUMGART, P (1998). Vascular ergotism through inhalation of grain dust. Deutsche Medizinische Wochenschrift. 123, 1547-50.

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