Molecules of Witchcraft

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Molecules of Witchcraft

• By Tanja Thompson
• Justin Reale

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Digitalis purpurea
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Digitalis purpurea

• Common Names
• Common foxglove
• Foxglove
• Long purples
• Dead mens fingers
• Toxic Amounts
• Therapeutic dose if 1.5g of powered leaf in an
  adult
• 800 to 1600mg is toxic to adults 1.

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History

• It is a cultivated flower so most of the recorded
  accounts of human poisonings come from reports of
  accidental ingestion of Digitalis purpurea that
  were gathered from gardens or from tea made from
  the leaves 1.

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Cardiac glycosides and Witchcraft

• Those branded for witchcraft often used cardiac
  glycosides derived from plants and animals such
  as toads in their "magic potions
• Cardiac glycosides caused individuals to "come
  back from the dead these effects were often
  blamed on the local herbalist AKA a witch 3.

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Human Toxicity

• Initially nausea and vomiting
• Hyperkalemia
• The cardiac effects include electrocardiogram
  changes
• Prolonged P-R interval
• S-T segment depression
• Bradycardia
• Heart block
• Ventricular tachycardia
• Mental confusion
• Lathargic
• Flashing of lights
• Halos around objects 1

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Chemically

• Glycosides are hydrolyzed to yield the secondary
  glycosides
• Digitoxin
• Gitaloxin
• More specifically digitoxin
• Considered a cardiac glycoside
• 2 Types of cardiac glysosides

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Cardiac glycosides(Pharmaceutical Class)

• Cardenolides are the most prevalent and are C23
  steroids with an ?, ?-unsaturated 5-membered
  lactone ring on C-17
• Examples digitoxin, convallatoxin, and evonoside

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Cardiac glycosides (Pharmaceutical Class)

• 2. Bufadienolides are C24 steroids with a double
  unsaturated 6-membered lactone ring on C-17
• Examples convallamarin, scillaren, A and B, and
  hellebrin 1.

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Mechanism of Action

• Digitalis and related glycosides
• Inhibition (or interference with pump) of the
  enzyme Na, K- ATPase, results in high
  intracellular levels of sodium and potassium.
• The increased Na leads to the subsequent increase
  in calcium levels with leads to over stimulation
  of muscle and cardiac tissue 1.

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Case Example

• A 70-year-old man mistook Digitalis purpurea
  leaves for comfrey leaves in preparing an herbal
  tea. He consumed one liter of tea over several
  days. He was admitted with a 2-day history of
  vomiting, diarrhea, confusion, and seeing
  flashing lights. The EKG demonstrated
  bradycardia and complete heart block, which
  reverted to first-degree block after four days.
  The potassium level was 6.8 mEq/l. He was
  treated with activated charcoal, atropine, and
  insulin. A temporary pacemaker was required.
  The EKG was normal after ten days 1.

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Claviceps purpurea
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Claviceps purpurea

• Common names
• Ergotamine
• Ergot of Rye
• Holy fire
• Saint Anthonys fire
• Occult fire and
• Saint Vitus dance
• Ergot is a parasitic fungus that forms on the
  head of the grain of the Claviceps purpurea.
• The fungus produces a dark purple fruiting body
  called the sclerotium that is then consumed along
  with the grain 2.

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Background History

• The fire relates to the terrible searing pain
  and blackened extremities caused by the
  progression of gangrene.
• The dance refers to twitching and convulsive
  contortions due to the neurological effects of
  some ergot alkaloid.
• 16th century used to strengthen uterine
  contractions 3.

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A Little More History

• 600 B.C. The Assyrians who noted a noxious
  pustule in the ear of grain.
• 400 B.C. - record of noxious grasses causing
  miscarriages in cattle in Persia.
• 944 A.D. - 40 thousand deaths in France 3.

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Witchcraft of Ergot Alkaloid

• Older women who lived on the outskirts of the
  community, many of which were herbalist or unable
  to afford flour, thus would have saved a woman
  from ergotism and the rest of the community was
  effected by the infected wheat.
• Many of these individuals were accused of being
  witches and casting spells on the whole community
  3.

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Witchcraft Continued

• May have been responsible for the Salem witch
  trials of 1692 because of the moist and wet
  conditions during the spring and summer allowing
  for ideal conditions for the fungi to grow in the
  communitys grain.
• 250 people, mostly women were accused, 19 were
  hung and stoned to death 3.

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Human Toxicity

• Nausea, vomiting, diarrhea, severe thirst,
  tingling of skin, skin hypoerfusion, and chest
  pain.
• Headache, fixed mitosis, hallucinations,
  delirium, hemiplegia, and convulsions may occur.
• Hemorrhagic vesiculations, prutius, formications,
  and gangrene can occur.
• Hallucinogenic episodes 2.

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Current Uses

• Ergotamine tartrate plus caffeine is administered
  to relieve migraine headaches.
• Ergononvine has been used to treat postpartum
  hemorrhage.
• Ergot derivatives are used to manage amenorrhea
  and an adjunct in the treatment of Parkinsons
  disease.
• Hydrogenated ergot alkaloids have been used for
  symptoms of idiopathic mental decline in elderly
  patients 2.

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Exposure Pathway

• Consumption of contaminated grain (especially rye
  flour)
• Acute poisoning in humans is rare and generally
  associated with overdosage with ergotamine
  tartrate medications.
• Ergot-containing mixtures
• has been associated with attempts to induce
  abortion.
• Animal poisoning
• consumption of contaminated pasture grasses and
  grains.
• Last known human death was in 1951 2.

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Chemically

• A mixture of ergot alkaloids
• Ergotamine
• Ergocistine
• Ergocornine
• a- ergocryptine
• ß-ergocryptine 2.

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Toxicokinetics

• Poorly absorbed orally
• The majority of the xenobiotic is eliminated by
  phase I biotransformation in the liver.
• Symptoms begin approximately 4hrs after ingestion
• Half-life of metabolism ranges from 1.4-6.2 hrs
  2.

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Mechanism of Action

• Interaction with
• Tryptaminergic, dopaminergic, and a-adrenergic
  receptors
• Pharmacological effects
• interference with a-adrenergic receptors
• producing pressor, uterotonic, and emetic effects
• Hypothermia is induced by action at dopamine and
  serotonin receptors
• Ergot amine poisoning may be attributed to
  localized vascular insufficiency 2.

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Works Cited

• 1. Spoerke, D. G., S. C. Smolinske. (1990).
  CRC toxicity of houseplants. Florida CRC Press,
  Inc 11-13, 122-123.
• 2. Wexler, P. (1998). Encylocopedia of
  toxicology Erogt. Academic Press Vol. I,
  560-561.
• 3. Le Couteur, P., J. Burreson. (2003).
  Napoleons buttons Great molecules in history.
  New York Tarcher/Putnam, 238-244, 228-229.