Foundations of Pharmaceutical Sciences

Exam 1

What are some drugs used in ancient times?

• Mead

• Beer and berry wines/wine

• Opium

• Alcohol

• Cannabis

• Poppy seeds (source of opium) / poppy juice

• Coca leaves (source of cocaine)

• Cohoba (made from mimosa beans)

• Tobacco (native americans)

• Quinine (derived from cinchona tree)

• Strychnine

What drugs are found in the bible?

• Alcohol

• Plants

• Olive Oil

What is alchemy?

Philosophical and experimental tradition merging early chemistry, metallurgy, physics, and mysticism. Used for two milennia

Who was a key player in alchemy? Why?

Isaac Newton

• wrote extensively on alchemical texts and performed private laboratory experiments in his pursuit of fundamental natural forces

Why is alchemy so important?

The foundation for modern pharmaceutical sciences

• Chrysopoeia: transmutation of base or common metals into noble metals

• Philosopher’s Stone: finding or creating a legendary mythical substance to catalyze transmutation

• Elixir of Life: discovering universal remedy to cure all diseases

• Spiritual Perfection: achieving the “Great Work”

When did pharmaceutical chemistry and pharmacology emerge as a scientific field?

End of 19th century

What did Paul Ehrlich do?

In 1906, he postulated synthetic chemicals for antimicrobials

1902 Biologics Control Act

• enacted in response to two incidents involving deaths of 22 children who had contracted tetanus from contaminated vaccines

• first tetanus vaccine discovered in 1924, penicillin in 1928 by alexander fleming

1906 Pure Food and Drug Act

• reaction to public outcry following the publication of “The Jungle” by Upton Sinclair

• ingredient labeling

• Adulteration prohibited

What time were most drugs not requiring prescription?

early 1930s

Major breakthroughs of Golden Era (1930-1960)

• Antibiotics (sulfonamides, penicillin)

• Synthetic vitamins

• Hormones (thyroxine, oxytocin, corticosteroids)

• Antihistamines

• Vaccines

• Oral contraceptives

Which hormone was the first to be used as a drug?

Adrenaline/epinephrine

Results of golden era

• infant deaths reduced

• Maternal deaths declined

• TB/Diphtheria, Pneumonia treated and cured

50% marketed drugs were all natural products

What caused the need for increasing safety regulations? What did it lead to?

• S.E. Massengill formulation tragedy:

• No animal testing done

• 100 deaths primarily children

Led to:

• 1938 Food, Drug, and Cosmetic Act

• 1962 amendment increased regulation for efficacy and safety

• Double blind study introduced

Major discoveries in small molecule drugs?

• Cardiovascular

• Anti-inflammatory

• Analgesic

• Chemotherapeutics

• Neurotherapeutics

• Psychiatric indications

• Contraceptives

Major concepts in golden era?

• Rational drug design

• Improved instrumentation

• Thalidomide Disaster

What does the R and S Thalidomide do?

• R: sedation

• S: teratogenic effects

What kept thalidomide off U.S. Market?

Dr. Francis Kelsey resisted intense corporate pressure to approve the drug and insisted on scientific rigor.

Manufacturer failed to show

• adequate safety daeta

• Clinical proof of efficacy

• How drug affected pregnant women and fetuses

• Richardson-Merrel thought glowing testimonials could substitute for science

Impact of Thalidomide Disaster

• >10,000 children born with malformations

• Led to passage of 1962 Kefauver-Harris Drug Amendments to FD & C Act, requiring drug makers to prove both safety and efficacy before marketing

• Caused development of Phase 1-3 clinical trials

Impact of HIV

• Therapeutics

• growth in immunology field

• Social pressures

Impact of Biotechnology

• Molecular biology (CRISPR, gene editing)

• Genome project

• Manufacturing advances

• Major growth in discovery and development of biologics