Section I INTRODUCTION TO TOXICOLOGY

Poisons and History Trial and Error!

A Brief History Natural Bioactive Compounds Definition of Toxicology Oxygen A Chronic Toxicant? Scope of Modern Toxicology Summary and Conclusions

I. A Brief History
The Ebers (papyrus) 1500 BC Discorides (employed by Nero) 50 BC de Medicis (employed by the Borgias) Middle Ages Bombastic Paracelsus 1500 AD Percival Pott (English Physician) 1775 AD Orfila (father of toxicology) early 1800s Pesticide Boom mid-1900s Rachel Carson (Silent Spring) early 1960s

The Ebers

Nicander

Dioscorides

Catherine de Medici

Bombastic Paracelsus

Percival Pott

Pesticide Boom of the 1900s

II. Natural Bioactive Compounds

Aspirin A Magic Bullet!

The Final Product

III. Definition of Toxicology

The study of toxic chemicals No! The study of the adverse effects of chemicals Yes! Paracelsus said it best: All substances are poisons; there are none that are not. Dose differentiates between a poison and a remedy.

Botox A Deadly Poison?

Botox How it Works

Botox The Inevitable Side Effect!

IV. 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

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Some Common Antioxidants

V. Scope of Modern Toxicology

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Specializations in the Field

VI. Conclusions
All substances are potentially toxic as well as nontoxic dose determines. Aspirin (from willow bark) is an example of an early magic bullet. Botox is another example of how dose determines effects. Even oxygen can be toxic. Toxicology = the study of adverse effects. Modern toxicology has many specializations.

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Drugs or Poisons?
Natural Bioactive Compounds Magic Bullets? Ergot Alkaloids Penicillins Opioids Tropane Alkaloids Summary and Conclusions

I. Natural Bioactive Compounds

Chemicals found in nature 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.

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.).

II. 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. Anthonys 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

III. 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.

Penicillin is Recognized as an Antibiotic

Chain and Florey in late 1930s isolated 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.

IV. 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
-Phenylethylamine backbone found in many mindaltering chemicals. Found in chocolate, it is lethal to dogs and may emulate love in humans!

V. Phytotoxin Example Tropane Alkaloids

Cocaine Atropine Scopolamine

Cocaines 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 John Pemberton mixed cocaine from the coca leaf with caffeine from the kola nut to make Coca Cola! Addictive, so outlawed in 1906.

Classic Coke
Today it is not really classic!

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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.

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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.

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VI. Conclusions
Natural bioactive compounds are magic bullets. Dose determines drugs versus toxins. Mycotoxins and phytotoxins represent two of the main sources of drugs today. Mycotoxins of importance include ergot alkaloids, penicillins, and cephalosporins. Phytotoxins of importance include the opioids and tropane alkaloids. Many new drugs are merely awaiting discovery!

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