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St. Anthony’s Fire. 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. Introduction.

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St. Anthony’s Fire

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St anthony s fire l.jpg

St. Anthony’s Fire


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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


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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


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Overview

  • History

  • Signs & Symptoms

  • Mechanism of Action

  • Drug Interactions

  • Treatment

  • Therapeutic Uses

  • LSD


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History

Eleusinian Mysteries

  • Religious cult between 1500BC and 396AD

  • Cult of Demeter and Persephone promising pleasant afterlife

  • Drank ritual drink kykeon before having visions of afterlife, hallucinations

  • Kykeon likely contained ergotized barley

  • Extremely secretive, death penalty for revealing secrets and visions


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Tollund Man

  • Perfectly preserved body found in Danish peat bog, from 400BC

  • Rope around neck, likely drowned as ritual sacrifice to earth goddess

  • Stomach contained porridge with very high levels of ergot in the barley

  • Ergotised porridge likely taken to induce hallucinations before ritual sacrifice


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Tollund Man


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Medieval Ergot Epidemics

  • Rhine Valley had many ergotism outbreaks recorded between 7th and 17th centuries, rye bread was staple food

  • Became known as St. Anthony’s Fire as monks of St. Anthony specialized in treatment

  • Also called Ignis Sacer and Holy Fire

  • 40 000 deaths in southern France in 944AD


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  • Convulsive ergotism called Dancing Mania, St. Vitus’s Dance, as people screamed, babbled, convulsed, and ‘danced’ in streets: shut down Strasbourg in 1418

  • Often attributed to demons and madness or divine intervention

  • Scientific breakthroughs in 1670s when ergotism was connected bread and later to ergotized rye; ergot life cycle identified in 1853


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Salem Witch Trials

  • 1692 Salem, Massachusetts had wet harvest, rye bread likely contaminated with ergot

  • 8 girls in Salem experienced hallucinations, convulsions, burning skin sensations

  • Pastor’s daughters affected

  • Immediately accused other women of bewitching them


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  • Those accused of witchcraft were mostly unpopular, poor, and non-churchgoing

  • Over 150 people imprisoned for witchcraft that year

  • 20 people executed, 5 died in prison


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Salem Witch Trials


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Russia

  • Ergotism very common until 1945

  • Rye bread was staple food in Russia until 1945, when potatoes were planted instead and pesticides/fungicides introduced

  • Government statistics show that areas with wet weather and rye crops had outbreaks of trembling, confusion, hysteria, and hallucinations

  • 1926, there were 10,000 confirmed cases of ergotism in Russia


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Ergot Scare: Pont-Saint-Esprit

  • 1951, French town of Pont-Saint-Esprit had 200 people suffering from confusion, hallucinations, ‘madness’, and cold extremities

  • 7 deaths and 50 people interred in insane asylums

  • Linked to bread

  • Misidentified as ergotism, later proved to be mercury poisoning


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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


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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


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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


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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


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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


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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


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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


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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


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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


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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


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Treatment

  • Treatment of hallucinations

    • Stopping exposure to

      toxin usually effective

    • Intracranial injection of

      combination serotonin

      and cholinergic drugs

      successful treatment

      in mice


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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


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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?


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Medicinal Uses

  • Pergolide

    • Anti-Parkinson

    • 1000x stronger than bromocriptine

    • Inhibits prolactin

    • Effects on leutinizing and growth hormone


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Medicinal Uses

  • Methysergide

    • Prophylactic migraine treatment

    • Activation of 5HT-1D receptors in cranial blood vessels

      • vasoconstriction

    • Linked to retroperitoneal fibrosis


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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


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Medicinal Uses

  • Methylergonovine

    • Used after delivery

    • Initiates strong contractions of uterine smooth muscle

    • Contract the uterus, prevent hemorrhage, promote placental passage


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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


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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


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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


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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


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LSD

  • Today it is part of the ‘party drug’ scene

    • Along with ecstasy and mushrooms


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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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References

  • UNKNOWN (1960). St. Anthony’s fire rekindled. Can Med Assoc Journal, 83, 658-9.

  • CAPORAEL, L. (1976). Ergotism: The Satan Loosed in Salem? Science Vol. 192

  • WONG, G. (2004). Ergot of Rye: History. University of Hawaii Department of Botany.

  • http://www.botany.hawaii.edu/faculty/wong/BOT135/LECT12.HTM

  • KATZUNG, B. (2004). Chapter 16: Histamine, Serotonin and the Ergot Alkaloids. Basic and Clinical Pharmacology, 9th Edition

  • HART, C. (1999). Drugs for Migraine. Modern Drug Discovery. 2 (2), 20-21, 23-24, 28, 31

  • FREDERICKSON, A. (1998). Mechanisms of LSD: a Glimpse into the Serotonergic System. Neurobiology and Behaviour (http://serendip.brynmawr.edu/bb/neuro/neuro98/202s98-paper3/Frederickson3.html)

  • EADIE, M. (1983). Ergotamine Pharmacokinetics in Man: An Editorial. Cephalalgia. 3(3):135-8

  • Nestler EJ, Hyman SE, Malenka RC. Molecular Neuropharmacology. McGraw Hill. (2001)

  • Golan DE, et al. Principles of Pharmacology, The Pharmacological Bases of Drug Therapy. Lippincott Williams & Wilkins. (2005)

  • Banhidy F, Acs N, Puho E, Czeizel AE. Ergotamine treatment during pregnancy and a higher rate of low birthweight and preterm birth. British Journal of Clinical Pharmacology (2007). 64(4):510-516.

  • Zanettini R, et al. Valvular heart disease and the use of dopamine agonists for Parkinson's disease. New England Journal of Medicine (2007). 4;356(1):39-46.


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References

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  • PREPELICZAY, S. (2002) Socio-cultural and Psychological Aspects of Contemporary LSD in Germany. Journal of Drug Issues. Spring2002, Vol. 32 Issue 2, 431-458

  • SCHNELL, B. et al. (2007) Compendium of Pharmaceuticals and Specialties

  • WINTER, J., HELSLEY, S., FIORELLA, D., RABIN, R. (1999). The acute effects of monoamine reuptake inhibitors on the stimulus effects of hallucinogens. Pharmacol. Biochem. Behav., 63, 507-13.

  • WONG, G. (2004). Ergot of Rye: History. University of Hawaii Department of Botany.

  • http://www.botany.hawaii.edu/faculty/wong/BOT135/LECT12.HTM

  • WOOLLEY, D.W. (1955).Production of abnormal (psychotic?) behavior in mice with lysergic acid diethylamide, and its partial prevention with cholinergic drugs and serotonin. Proc NatlAcadSci, 41(6): 338-344.

  • WOOLTORTON, E. (2003). Risk of stroke, gangrene from ergot drug interactions. CMAJ, 168.

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References

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