DRUG DEVELOPMENT AND REGULATION - Basic Science Core

Pharmacology Exam 1

What are Drugs

Drugs are chemical substances used to diagnose, prevent, or treat diseases, and to prevent pregnancy.

What is the origin of Drugs

Use of “medicines” dates back to prehistoric times

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• Mixture of religion and use of plant substances has been common since religion and men have existed

• Humans have sought plant and animal products since the earliest of times to combat sickness and death (Campbell, 2007, p. 2)

• Many of these products were discovered by trail and errors

• The initial treatments caused more harm than good, killing many!!!

Doctrine of Signatures (1500s)

Plant parts that resembled human body parts, animals, or other

objects were thought to have useful relevance to those parts, animals,

or objects

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• People thought that God had made herbs for the use of men and given them particular Signatures that could be read to cure disease, such as

• Walnuts were good to cure ailments of the head because they had a perfect signature for the head!

• The holes in the leaves of Saint Johns Wort resemble pores of the skin and, therefore, can treat disease and wounds of the skin

Oldest prescriptions were found …

• Oldest prescriptions were found on clay tablets written by Sumerian physicians around 3000 BC

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• Sumerians were one of the earliest urban societies to emerge in the world, in Southern Mesopotamia (modern day Iraq), more than 5000 years ago

Hippocrates (5th century BC) promoted the idea that disease results from:

• Natural causes rather than evil spirits

• He believed that the body had abilities to recuperate from disease

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• In the early years, medicines were developed by isolation and use of nature substances from botanical, mineral, and animal sources

• In modern times, medicines are developed by chemical synthesis of compounds that have biological activity

Drug Discovery Took Two Paths

• Path #1 – Isolation and use of nature substances from botanical, mineral and animal sources

• Path #2 – Later years – chemical synthesis of compounds having biological activity

PERUVIAN (CINCHONA) BARK

• 1630 – PERUVIAN (CINCHONA) BARK TO TREAT MALARIA

• Bark contained Quinine

Quinine

• Quinine is still used today as a drug of choice against malaria

• First specific drug to be used to treat an infectious disease

Digitalis (HISTORICAL PERSPECTIVES)

William Withering’s use of purple foxglove (digitalis purpurea) in 1783, lead to the isolation of digitalis

• He made a tea to treat the edema of cardiac “dropsy” (congestive heart failure)

• Digitalis is still the drug of choice for congestive heart failure

• Natural is much cheaper the chemical ones

Morphine

• The German chemist, Friedrich Serturner, isolated the alkaloid morphine from opium in 1805

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• Opium, a narcotic is used for pain control

• Opium had been used as a medical and recreational drug since prehistoric times

Caffeine (History)

The history of coffee goes at least as far back as the 13th century

• From Ethiopia

• Synthesized by the Arabs

Caffeine Function & Effects

• Caffeine works by stimulating the CNS, heart, and muscles

• It relieves mental and physical fatigue and increases mental alertness

Atropa belladonna (Devil's cherries)

• The entire plant is extremely poisonous

• Belladona = an enchantress of exceeding loveliness

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Two alkaloid substances isolated from plant

• Atropine

• Dilates the pupils (medicinal use)

 Belladonna plasters often applied after a fall

to the injured or sprained part

 Ingestion in excess amounts is a poison

Atropine

• Discovered in 1830s

• Led to discovery of neurotransmitter acetylcholine

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Belladonna blocks acetylcholine binding to muscarinic receptors,

• thereby reducing smooth muscle activity

Scopolamine

• Extracted from Japanese Belladona)

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• Used for motion sickness , sedative, truth serum, and mydriasis

DISCOVERY OF ASPIRIN

1) 1763 – Vicar Edward Stone (England) bark of willow tree reduced fever

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2) 1828 – German chemist Johann Andreas Buchner isolated salicin, active extract from bark

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3) 1829 – Henri Leroux, French pharmacist isolated larger quantities

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4) Raffaele Piria, Italian chemist converted to a sugar, which when oxidized formed salicylic acid

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5)1897 – aspirin first synthesized by Felix Hoffman, German chemist working for the Bayer company

ASPIRIN (Facts)

• Converted salicylic acid to the acetyl derivative

• Acetylsalicylic acid = “ASA” = also known as aspirin

• Single most important drug discovery in medicine

Sulfa (History)

• 1932: German biochemist Gerhard Domagk tested the red dye Prontosil.

• After a small chemical change, it became effective against streptococcal infections in mice.

• He identified the active ingredient as sulfanilamide—one of the first antibiotics.

• First effective treatment for pneumonia, meningitis, and other bacterial infections.

• Came before penicillin in clinical use.

• WWII: Sulfa powder and tablets were widely used by combat medics, saving many lives.

• Today: Sulfa drugs are commonly used to treat urinary tract infections (UTIs).

SULFONAMIDES (“SULFA” DRUGS) Deaths 1935

• Over 100 deaths across 15 states

1938 Food, Drug, and Cosmetic Act

Which required companies to perform animal safety tests on their proposed new drugs and submit the data to the FDA before being allowed to market their products.

Discovery of Penicillin

• 1928

• Sir Alexander Fleming

World War 2 & Antibiotics

Prior to and in the early years of WWII, sulfa was distributed to soldiers as a powder to sprinkle on wounds

• Too much sulfa was damaging to the kidneys

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• By the end of WWII, penicillin had taken its place

PENICILLIN (Historical)

The first patient was successfully treated for streptococcal septicemia in the United States in 1942.

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• Penicillin helped reduce the number of deaths and amputations of troops during World War II

DRUG DEVELOPMENT

DRUG DEVELOPMENT

Time necessary to develop a drug is averages 12 years

• Cost of developing a drug approximates $1.6B from concept to market

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• 1 in 1000 potential drugs makes it to testing in human trials

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• 9 out of 10 fail in human testing

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• Human testing (clinical trials) costs millions

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• Patent = 20 years

STAGES OF DRUG DEVELOPMENT (5)

1) Synthesis or discovery of new chemical from test tube or plan

2) Safety evaluation in animals and humans

3) Effectiveness evaluation in humans

4) Review of new drug application

5) Post-marketing surveillance to report all adverse effects