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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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introduction
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
introduction3
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
overview
Overview
  • History
  • Signs & Symptoms
  • Mechanism of Action
  • Drug Interactions
  • Treatment
  • Therapeutic Uses
  • LSD
history
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
tollund man
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
medieval ergot epidemics
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
slide9
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
salem witch trials
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
slide11
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
russia
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
ergot scare pont saint esprit
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
signs and symptoms
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
gangrenous symptoms
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
convulsive symptoms
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
kinetics
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
mechanism of action
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
mechanism of action20
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
mechanism of action21
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
mechanism of action22
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
treatment
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

treatment24
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
treatment25
Treatment
  • Treatment of hallucinations
    • Stopping exposure to

toxin usually effective

    • Intracranial injection of

combination serotonin

and cholinergic drugs

successful treatment

in mice

treatment26
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
medicinal uses
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?
medicinal uses28
Medicinal Uses
  • Pergolide
    • Anti-Parkinson
    • 1000x stronger than bromocriptine
    • Inhibits prolactin
    • Effects on leutinizing and growth hormone
medicinal uses29
Medicinal Uses
  • Methysergide
    • Prophylactic migraine treatment
    • Activation of 5HT-1D receptors in cranial blood vessels
      • vasoconstriction
    • Linked to retroperitoneal fibrosis
medicinal uses30
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
medicinal uses31
Medicinal Uses
  • Methylergonovine
    • Used after delivery
    • Initiates strong contractions of uterine smooth muscle
    • Contract the uterus, prevent hemorrhage, promote placental passage
slide32
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
slide33
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
slide34
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
slide35
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
slide36
LSD
  • Today it is part of the ‘party drug’ scene
    • Along with ecstasy and mushrooms
references
References
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references38
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  • http://www.botany.hawaii.edu/faculty/wong/BOT135/LECT12.HTM
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  • 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)
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