Era of Pure Drugs

The second millennium in Europe however saw the beginning of a slow erosion of the preeminent position held by plants as sources of therapeutic effects. This began with the ‘Black death’ due to plague and syphilis that raged through Europe, which the then dominant Four Element (referring to the four humors) medical system seemed powerless to stop. A century later Paracelsus (1493–1541), an itinerant Swiss surgeon, with his introduction of active chemical drugs such as arsenic, copper sulphate, iron, mercury and sulphur became an important advocate of chemically prepared drugs. These were accepted even though they had toxic effects because of the urgent need to treat syphilis. Eventually as the efficacy of some of these drugs became known, they entered professional medical practice. This preparation of medicines was an important milestone in the history of pharmacy in the western world. Through the 16th, 17th and 18th centuries subsequent rapid advances in Chemistry made it a separate profession. Isolation of some opium alkaloids in the early 19th century was a key event in the development of modern pharmacy. This was because, it showed that isolated compounds could have the same activity as the crude drug from which they were isolated. This paved the way for introduction of pure compounds for treatment, the corner stone of current modern western medicine.

For a period of about 300 years a small minority of practising pharmacists made significant investigations into the chemistry of drugs, and along the way isolated many drugs used even today and contributed much to the general chemical knowledge.

William Withering (1741–1799) discovered the use of Digitalis from preparations popularly given by an old ‘witch’ (woman herbalist) doctor for dropsy. Later in 1875 digitoxin, the active fraction of Foxglove, was isolated and its chemical structure identified in 1928. Although the advent of new diuretics and vasodilators has added to the repertoire of heart medicines, there is still no alternative to digitalis for the first line treatment of fast atrial fibrillation.

The great expansion in the knowledge of chemistry in the 19th century, much extended the herbal pharmacopoeia that had previously been established. Building on the work of Lavoisier, chemists throughout Europe refined and extended the techniques of chemical analysis. Acetic acid synthesis by Kolbe in 1845 and methane synthesis by Berthelot in 1856 saw the beginnings of organic chemistry.

Pharmacognosy, which until then dealt with medicinal products of plant, animal or mineral origin in their crude state, was taken over by physiological chemistry. The focus shifted from finding new medicaments from the vast world of plants to finding active principles that accounted for their pharmacological properties.

Earlier isolation of morphine from opium by German apothecary Friedrich Wilhelm Adam Serturner (1783–1841), emetine from Ipecac in 1817 and quinine and cinchonine from Cinchona in 1820 by P.J. Pelletier (1788–1842) and J.B. Caventou (1795–1877), strychnine and brucine from nux vomica in 1818 paved the way for modern phytochemistry, and this was followed by the isolation of several active principles from plant drugs each of which began to get added to the arsenal of pure drugs.

Not only were these pure drugs rapidly adopted by physicians because their potency was assured, but their existence also allowed physiologists to administer drugs accurately during their research, which became the wellspring of modern pharmacology.

Thus commercialization of herbal single ingredients became more apparent and plant drugs popularly used as drugs in several indigenous medical systems began to be screened for newer drugs with enormous success. Reserpine the anti-hypertensive and tranquillizer isolated from Sarpagandha or Rauwolfia serpentina indicated in Ayurveda for paralysis and insanity, ephedrine the bronchodilator from Ma-Huang of Chinese medicine prescribed for inflammatory conditions, narcotics codeine and morphine from opium are some such drugs isolated from plants of ethnomedical usage. Niemann isolated cocaine in 1860 and the active ingredient, physostigmine, from the Calabar bean in 1864. As a result of these discoveries and the progress made in organic chemistry, the pharmaceutical industry came into being at the end of the 19th century.

In the past two centuries, modern methods of isolation and pharmacological screening have yielded numerous such purified compounds which have proven to be indispensable to modern medicine. These include atropine, bulbocapnine, cocaine, codeine, colchicines, ephedrine, hyoscyamine, ipecac, morphine, papaverine, physostigmine, picrotoxin, pilocarpine, pseudoephedrine, quinidine, reserpine, scopolamine, strychnine and d-tubocurarine.

Parallel developments in related fields namely the invention of the microscope by Zacharias Jansen in 1595, visualization of cells by Robert Hooke in 1665, Joseph Lister’s theory of antisepsis, Louis Pasteur’s identification of microbial origin of disease were followed by significant advances in medicine and chemistry.

The synthesis of urea in 1828 by German Chemist Friedrich Wöhler from ammonium cyanate gave birth to synthetic organic chemistry. This synthesis of organic molecules, a radical new direction in chemistry combined with more traditional analytical approaches revolutionized chemistry leading to a deep understanding of the fundamental principles of chemical structure and reactivity. The beginning of synthetic medicinal chemistry was made in Germany with the synthesis of chloral hydrate in 1869. This was followed by several others: to name a few, paraldehyde in 1882, sulphone in 1888, phenacetin in 1889 and aspirin in 1899.

Likewise, outstanding work of Paul Ehrlich, discovery of penicillin from fungal source by Alexander Fleming, discovery of sulpha drugs, etc. began adding to the ever-growing arsenal of newer drugs from various sources including plants, microbes and chemical synthesis.

As chemical methods became more prevalent in medical practice, pharmacists were forced to learn new methods of preparation and manipulation. The volume of chemical discoveries made by pharmacists is enormous.

The knowledge related to drugs having become unwieldy with different distinct areas of expertise, the study of medicinal substances which were no longer only plant derived became subdivided into the following areas to be pursued exclusively:

  • Pharmaceutical chemistry—including the theory and fundamentals of scientific chemistry with emphasis on chemical substances of medicinal importance.
  • Pharmacy or Pharmaceutics—concerned with the modes of treatment of chemicals or crude drugs in the preparation of galenicals and medicines in forms suitable for administration.
  • Pharmacology—study of biological effect of drugs on organisms.
  • Pharmacognosy—the objective study of crude drugs of animal, vegetable and mineral origin treated scientifically, which meant the study of their structural, physical, chemical and sensory characters including their history, cultivation and collection and other processing they undergo between the supplier and manufacturer.

As can be seen, since pharmacognosy is the starting point of all these specializations, it is considered the mother of other facets of pharmaceutical sciences.


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