Lecture 1

Question 1

Pharmacology

Answer 1

The study of the beneficial effects of chemical
agents on biological systems. From the Greek pharmakos
(φάρμακον) for “medicine” and logos (λόγος) for “reason” or
“knowledge”.

Question 2

Toxicology

Answer 2

The study of the adverse effects of chemical agents
on biological systems. From the Greek toxikos (τοξικός) for
“poisonous” and logos (λόγος) for “reason” or “knowledge”.

Question 3

Subdivisions of Toxicology

Answer 3

1. Analytical:
   -Clinical: Measuring things, such as in hospitals (urine, blood…etc)
   -Forensic: Similar to clinical except that there is a legal aspect to it.
   -Biomonitoring: Monitor of biological pollutants in the human body. (Drug Testing)
   -Therapeutic Drug Monitoring: Monitoring of drugs for treatments.
2. Drug Development:
   -Pre clinical testing: Animal testing or in vitro.
   -Clinical trials: Human testing.

Question 4

What did early humans use as natural toxins for?

Answer 4

– Animal venoms.
– Toxic metals.
– Plant extracts.
– Hunting.
– Warfare.
– Assassination.

Question 5

What is the Ebers Papyrus?

Answer 5

It was a scroll found in Egypt in the 1870s containing 700 drugs in 900 formulas. Contains
indications, dosages, and appropriate spells and incantations.

Question 6

Hippocrates

Answer 6

Early physician, defined “effective dosages” of toxins and described bioavailability (How well a drug is absorbed).

Question 7

Socrates

Answer 7

Hemlock poisoning. (Greeks used it as an execution method).

Question 8

Dioscorides

Answer 8

(Materia Medica; plant, animal, and mineral toxins).
– Discovery of Belladonna (scopolamine).
– Discovery of Foxglove (digitalis).

Question 9

Avicenna (ibn Sina)

Answer 9

First to suggest clinical trials.

Question 10

Paracelsus

Answer 10

German physician/alchemist.
– Defined the “toxicon”.
– Experimentation and observation.
– Therapeutic vs. toxic dose.
– Specificity of response

Question 11

What is meant when Specificity of response is used?

Answer 11

Specificity is targeted to one site. (Like heart medication)

Question 12

Who said “All substances are poisons. There is none that is not
a poison. The right dose differentiates poison from a
remedy”?

Answer 12

Paracelsus

Question 13

Who is the “father of toxicology”?

Answer 13

Paracelsus

Question 14

Lady Toffana

Answer 14

“Queen of Poison”; arsenic cosmetics; established
dose and time relationship.

Question 15

Hieronyma Spara

Answer 15

“Italian Widows Club”; would sell arsenic for gold.

Question 16

Borgias

Answer 16

Pope Alexander VI

Question 17

Catherine de Medici

Answer 17

Systematic study of the effects of poisons on
the sick and poor to make sure the “correct” formulation was
delivered to her customers.

Question 18

Percival Potts

Answer 18

Discovered that chemicals can cause cancer. Scrotal cancer from chimney soot exposure.

Question 19

Mathieu Orfila

Answer 19

Forensic/analytical toxicology. Considered to be the first toxicologist.

Question 20

Paul Ehrlich

Answer 20

Mechanistic toxicology and phramacology, “magic bullet” concept. (Drug is designed to hit one target).

Question 21

Alice Hamilton

Answer 21

Occupational toxicology

Question 22

What did Percival Potts discover?

Answer 22

Young poor boys (Age 4-7) that would clean chimneys would after time developed scrotal cancer due to the exposure to chemicals and poor hygiene conditions.

Question 23

~400 BC: Hippocrates

Answer 23

discovers pain relief treatments with
powder made from the bark and leaves of the willow tree
(Salix sp.) (Analgesic)

Question 24

1897: Felix Hoffman

Answer 24

a chemist at Bayer, synthesized
acetylsalicylic acid and tested it on his arthritis-suffering
father. (aspirin was created).

Question 25

Johann Pagenstecher

Answer 25

1830: Swiss pharmacist isolated salicin
as the active ingredient in Meadowsweet

Question 26

Bayer receives patent for acetylsalicylic acid (Aspirin).

Answer 26

1899

Question 27

Aspirin sales?

Answer 27

Sales today exceed 50 billion pills per year.

Question 28

What is the “horse named jim” incident?

Answer 28

– Tetanus contaminated horse serum was used to produce
a diphtheria antitoxin.
– Contaminated vaccine.
– Caused the deaths of 13 children in St. Louis, MO.

Question 29

What did the “horse named jim” incident lead to?

Answer 29

The 1906 Pure Food and Drugs Act

Question 30

The 1906 Pure Food and Drugs Act

Answer 30

-Food or drug label could not be false or misleading, but no requirement
for safety or efficacy testing.
-Levels of eleven dangerous ingredients, including alcohol, heroin, and
cocaine, had to be listed

Question 31

Elixir of Sulfanilamide

Answer 31

– The first antibiotic “wonder drug”.
– In one batch, diethylene glycol (Antifreeze) substituted for
propylene glycol (Used as a way to dissolve drugs).
– Proved deadly; 100+ die after taking
reformulated product (1937)
– Caused acute kidney failure

Question 32

What did the incident with the Elixir of Sulfanilamide lead to?

Answer 32

Federal FD&C Act of 1938

Question 33

Federal FD&C Act of 1938

Answer 33

Mandated pre-market safety approval of all new drugs, however,
drugs did not have to be proven effective.
Pharmaceutical companies must submit “New Drug Application”
(NDA) to FDA prior to marketing.

Question 34

Thalidomide

Answer 34

Used for morning sickness in Europe, caused severe birth defects (Not necessarily lethal).

Question 35

Frances Kelsey

Answer 35

FDA reviewer who had concerns of safety about Thalidomide. Drug was not approved for sale in the US.
Lead to the Kefauver-Harris Drug Amendments of 1962

Question 36

Kefauver-Harris Drug Amendments of 1962

Answer 36

Mandated both pre-market safety and effectiveness
Regulated prescription drug advertising. (side effects and contraindications).
FDA given right to withdraw drugs from market