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What is Toxic – Are They Drugs or Poisons?
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Paracelsus Revisited!
Natural Bioactive Compounds – Magic Bullets?
Scope of Modern Toxicology
Some Conclusions
Paracelsus Revisited!
“All substances are poisons; there are none that are not. Dose differentiates between a poison and a remedy.”
Natural Bioactive Compounds
Natural chemicals that cause biochemical or physiological actions in organisms.
Phytotoxins – Bioactive chemicals from plants.
Mycotoxins – Bioactive chemicals from molds and fungi.
Both classes represent the two main sources of drugs on the market today.
Aspirin – A Magic Bullet!
The Final Product
Botox – A Deadly Poison?
Botox – How it Works
Botox – The Inevitable Side Effect!
Oxygen – A Chronic Toxicant?
Some Oxidants from Oxygen
O2-. – Superoxide Anion
HOO. – Peroxyl Radical
H2O2 – Hydrogen Peroxide
HO. – Hydroxyl Radical
Free Radicals – Reactive chemicals missing a valence electron, thus on an “electron search.”
The Effects of Oxidants
Anti-Oxidants
Common Natural Drug Types
Analgesics – cause temporary pain relief (aspirin, etc).
Narcotic analgesics – produce a sleep-like painless state (morphine, codeine, etc).
Anesthetics – block pain nerves (cocaine, etc).
Stimulants – stimulate activity (caffeine, nicotine, etc).
Sedatives – produce general sedation (alcohol, etc.).
Antimicrobials – cure infectious diseases (penicillins, etc.).
Mycotoxin Example – Ergot Alkaloids
Produced by molds that infest stored grains (rye).
Noted as far back as 600 BC by the Assyrians.
Caused gangrenous and convulsive ergotism (St. Anthony’s Fire).
Symptoms included convulsions, hallucinations, gangrene and spontaneous abortions.
Used as a drug for migraines and abortions.
Today – fumigants used to avoid mold growth.
Gangrenous Ergotism
Mycotoxin Example – Penicillins
Produced by fruit, bread and other food molds.
Possibly first used by Egyptians, native Americans.
Pasteur noted in late 1800s that molds (Penicillium spp.) could kill bacteria.
Fleming in 1928 discovered by accident that molds killed staphylococcus bacteria.
Fleming’s Accidental Discovery
Penicillin is Recognized as an Antibiotic
Chain and Florey in late 1930s isolate the drug.
Useful against many types of infections – pneumonia, gangrene, gonorrhea, bone infections, etc.
Early on, was expensively produced in broths.
The drug was extracted from patients’ urine for re-use.
Later was inexpensively mass produced.
Led to later discovery of others – cephalosporins, etc.
An “internal pesticide.”
Penicillin is Mass Produced
Some Types of Penicillins
Resistance develops when bacteria can break it down.
New types of “resistant” forms are marketed.
Phytotoxin Example – Opioids
Sumerians probably first to notice narcotic effects of the dried sap of the opium poppy (Papaver somniferum).
“Narcotic” from Greek “narkotikos,” meaning stupefying.
Opioids dull senses and induce sleep.
Arab physicians used opium for dysentery and traded it to Asia.
Paracelsus introduced it to Europe in the 1500s.
Used for pain relief and diarrhea.
The Opium Poppy
Isolation of the Active Ingredients
In 1803, morphine (10%) was isolated from the sap.
In 1832, codeine and papaverine were isolated.
During and after the Civil War morphine was combined with alcohol as laudanum. Given for old war injuries.
The Problem with Opioids
In 1898, heroin was produced from morphine. A great cough suppressant, but also very addictive.
Opioids may cause the release of powerful pain relievers in the brain – endorphins.
Some Natural and Synthetic Opioids
A Common Backbone
b-Phenylethylamine backbone found in many mind-altering chemicals.
Found in chocolate, it is lethal to dogs and may emulate love in humans!
V. Phytotoxin Example – Tropane Alkaloids
Scopolamine
Cocaine’s Origin
Produced by the Andean coca bush.
Natives chewed leaves to alleviate hunger and fatigue.
Isolation of Cocaine
Cocaine was isolated in 1860.
Caused numbness of the tongue – local anesthetic.
Freud created first cocaine addict by using it to wean a colleague off morphine addiction!
By the late 1880s used widely as a local anesthetic for dentistry and ophthalmology.
Also used in a famous elixir!
Cocaine as an Elixir
In the 1880s, Atlanta druggist mixed cocaine from the coca leaf with caffeine from the kola nut to make…
Coca Cola!
Addictive, so outlawed in 1906.
Classic Coke
It was not really classic.
Non-Addictive Local Anesthetics
Atropine – Belladonna Poison
A classical poison used in the Middle Ages.
Isolated from the deadly nightshade (Atropa belladonna).
Atropos = of the 3 Fates, the one that cuts the string of life.
Known to the ancient Hindus.
Atropine – Current Uses
Historically used to dilate pupils – a sign of beauty.
Used by ophthalmologists to dilate pupils for exams.
Used by the military as an antidote for war gases.
Scopolamine – Henbane Poison
A poison related to atropine.
Isolated from the henbane (hyoscyamus niger).
A powerful sedative.
Used to treat motion sickness.
Scope of Modern Toxicology
Specializations in the Field
Some Conclusions
All substances are potentially toxic as well as non-toxic – dose determines.
Natural bioactive compounds are “magic bullets.”
Dose mainly determines drugs versus poisons.
Many new drugs are merely awaiting discovery!
Modern toxicology has many specializations.
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