Module 1: The Development of Pharmaceutical Industry

WHAT HAPPENED DURING THE EARLY YEARS?

1. Disease has been recognized as an enemy of humankind, it is an affliction by the gods.

2. Egyptian therapies focused on purging the affliction, appeasing deities.

3. Greeks became essentially theoretical following four basic concepts: humours: black bile, yellow bile, blood, phlegm became the framework of health and disease.

4. Greek medicine placed a rather little emphasis on herbal remedies. It was in the mid 19th century that chemistry and biology advanced sufficiently.

19th Century

• Control of scurvy (Lind, 1793)

• Vaccination (Jenner, 1798)

• Surgical infection using Aseptic Techniques (Semmelweis, 1861)

• British Pharmacopoeia (1864)

 Three essential strands in 19th century

• Evolving science of biomedicine

• Emergence Of Synthetic Organic Chemistry

• Development Of Chemical Industry In Europe

Events in Development of Biomedicine (4)

Cell theory

Birth of Pharmacology as Scientific Medicine

Germ theory of disease

Chemotherapy

Cell theory

Rudolf Virchow

Birth of Pharmacology as Scientific Discipline

Rudolf Buccheim

Magendie and Claude

Germ theory of disease

Louis Pasteur

Airborne infection was the underlying cause

Germ theory disease

Chemotherapy

Paul Ehrlich

Drug for Syphilis

Compound 606 / Salvarsan

Developments in Chemistry (6)

Diethyl Ether

Nitrous Oxide

Amyl Nitrite

Aniline

Establishment of Rules of Valency

Benzene

Sweet oil of vitriol

Diethyl ether (1950)

Stupefying agent

Nitrous oxide

A potent vasodilator

First therapeutic drug to come from synthetic chemistry

Amyl nitrite

Precursor for mauvein

Aniline

Who accidentally discovered mauvein?

Perkin

Apothecaries trade (5)

1. Physicians felt the need to issue prescription

2. Isolation of substances from plant extracts

3. Companies start to flourish

4. Synthetic chemistry became the source of mew compounds starting with aniline-based dye

5. Separation of apothecaries and medical trade from dyestuff industry

First alkaloid

Morphine

___________ are nitrogen containing compounds

Alkaloids

First local apothecary in 1827

Merck

Who purified adrenaline?

Parke davis and Eli lilly

2 Principles in Apothecaries Trade

1. Principle of Biomedicine

2. Principle of Chemistry

Understanding how disease and drugs work respectively

Principle of Biomedicine

Going beyond color, crystallinity, but an understanding of the structure and properties of molecules and how to synthesize them in the laboratory

Principle of Chemistry

20th century (6)

1. Antipyretics

2. Chloral hydrate

3. Barbital

4. Urea

5. Procaine

6. Cocaine

First nonvolatile CNS depressant

Chloral hydrate

By Von Mering and Fischer

Barbital

By Hilaire

Urea

First local anesthetic drug

Procaine

Had local anesthetic action in the eye

Cocaine

Chemistry driven discoveries

1. Synthetic chemistry

2. Natural product chemistry

Based on the chemical structure rather than the site/ mode of action

Principle of chemistry

Pharmaceutical industry has difficulty in synthesizing structures

Natural Product Chemistry

Concept of Chemotherapy

Target driven discoveries

Agents only work when they are bound

Corpora non agunt nisi fixata

Saved life of Domagk’s daughter

Prontosil

Antimetabolite Principles

by hitching and elions 1945

Interest in the synthesis of folic acid, purines, and pyrimidines as chemotherapeutic agents

Identified dihydrofolate reductase

Emergent drugs (6)

1. Pyrimethamine

2. Trimethoprim

3. 6-mercaptopurine

4. Azathioprine

5. Aciclovir

6. Zidovudine

James Black and Receptor-Targeted Drugs (3)

1. Ligand-receptor interactions

2. Beta-adrenoceptor blocking agent

3. H2-receptor antagonist

First to have action on H2 receptors in healthy human volunteers

Burimamide (1972)

Accidental Clinical Disciveries (5)

1. Digitalis - in treating dropsy

2. Antidysrhythmic effect of quinine

3. Amphetamine to treat ADHD

4. Laborit’s discovery of Phenothiazide

5. Promethazine causing sedation

Rational drug design

Ability to predict the appropriate molecular structure of a drug based on information about its biological receptor

Questions asked about rational drug design (2)

1. What is the unmet need (prevalent disease)?

2. What substance causes the disease?

Targets of rational drug design regarding druggability

1. Druggable

2. Non-druggable

Criteria for Rational Drug Design

1. Safety

2. Targeted

3. Less toxic

4. Cost

5. Molecular Structure of Drug

Current trends in drug discovery

Computational Chemistry and Computer-Aided Drug Design (CADD)