The ancient Chinese wrote extensively on medical subjects. The Pen Tsao, for instance, was written about 2700 b.c. and contained classifications of individual medicinal plants as well as compilations of plant mixtures to be used for medical purposes. The Chinese doctrine of signatures (like used to treat like) enables us to understand why medicines of animal origin were of such great importance in the Chinese pharmacopoeia.
Ancient Egyptian medical papyri contain numerous prescriptions. The largest and perhaps the most important of these, the Ebers papyrus (1550 b.c.), contains about 800 prescriptions quite similar to those written today in that they have one or more active substances as well as vehicles (animal fat for ointments; and water, milk, wine, beer, or honey for liquids) for suspending or dissolving the active drug. These prescriptions also commonly offer a brief statement of how the preparation is to be prepared (mixed, pounded, boiled, strained, left overnight in the dew) and how it is to be used (swallowed, inhaled, gargled, applied externally, given as an enema). Cathartics and purgatives were particularly in vogue, since both patient and physician could tell almost immediately whether a result had been achieved. It was reasoned that in causing the contents of the gastrointestinal tract to be forcibly ejected, one simultaneously drove out the disease-producing evil spirits that had taken hold of the unfortunate patient.
The level of drug usage achieved by the Egyptians undoubtedly had a great influence on Greek medicine and literature. Observations on the medical effects of various natural substances are found in both the Iliad and the Odyssey. Battle wounds frequently were covered with powdered plant leaves or bark; their astringent and pain-reducing actions were derived from the tannins they contained. It may have been mandrake root (containing atropinelike substances that induce a twilight sleep) that protected Ulysses from Circe. The oriental hellebore, which contains the cardiotoxic Veratrum alkaloids, was smeared on arrow tips to increase their killing power. The fascination of the Greeks with the toxic effects of various plant extracts led to an increasing body of knowledge concerned primarily with the poisonous aspects of drugs (the science of toxicology). Plato's description of the death of Socrates is an accurate description of the toxicological properties of the juice of the hemlock fruit. His description of the paralysis of sensory and motor nerves, followed eventually by central nervous system depression and respiratory paralysis, precisely matches the known actions of the potent hemlock alkaloid, coniine.
The Indian cultures of Central and South America, although totally isolated from the Old World, developed drug lore and usage in a fashion almost parallel with that of the older civilization. The use of drugs played an intimate part in the rites, religions, history, and knowledge of the South American Indians. New World medicine also was closely tied to religious thought, and Indian cultures treated their patients with a blend of religious rituals and herbal remedies. Incantations, charms, and appeals to various deities were as important as the appropriate application of poultices, decoctions, and infusions.
Early drug practitioners, both in Europe and South America, gathered herbs, plants, animals, and minerals and often blended them into a variety of foul-smelling and ill-flavored concoctions. The fact that many of these preparations were so distasteful led to an attempt to improve on the "cosmetic" properties of these mixtures to ensure that patients would actually use them. Individuals who searched for improved product formulations were largely responsible for the founding of the disciplines of pharmacy (the science of preparing, compounding, and dispensing medicines) and pharmacog-nosy (the identification and preparation of crude drugs from natural sources).
There has long been a tendency of some physicians to prescribe large numbers of drugs where one or two would be sufficient. We can trace the history of this polypharmaceutical approach to Galen (a.d. 131-201), who was considered the greatest European physician after Hippocrates. Galen believed that drugs had certain essential properties, such as warmth, coldness, dry-ness, or humidity, and that by using several drugs he could combine these properties to adjust for deficiencies in the patient. Unfortunately, he often formulated general rules and laws before sufficient factual information was available to justify their formulations.
By the first century a.d. it was clear to both physician and protopharmacologist alike that there was much variation to be found from one biological extract to another, even when these were prepared by the same individual. It was reasoned that to fashion a rational and reproducible system of therapeutics and to study pharmacological activity one had to obtain standardized and uniform medicinal agents.
At the turn of the nineteenth century, methods became available for the isolation of active principles from crude drugs. The development of chemistry made it possible to isolate and synthesize chemically pure compounds that would give reproducible biological results. In 1806, Serturner (1783-1841) isolated the first pure active principle when he purified morphine from the opium poppy. Many other chemically pure active compounds were soon obtained from crude drug preparations, including emetine by Pelletier (1788-1844) from ipecacuanha root; quinine by Carentou (1795-1877) from cinchona bark; strychnine by Magendie (17831855) from nux vomica; and, in 1856, cocaine by Wohler (1800-1882) from coca.
The isolation and use of pure substances allowed for an analysis of what was to become one of the basic concerns of pharmacology, that is, the quantitative study of drug action. It was soon realized that drug action is produced along a continuum of effects, with low doses producing a less but essentially similar effect on organs and tissues as high doses. It also was noted that the appearance of toxic effects of drugs was frequently a function of the dose-response relationship.
Until the nineteenth century, the rapid development of pharmacology as a distinct discipline was hindered by the lack of sophisticated chemical methodology and by limited knowledge of physiological mechanisms. The significant advances made through laboratory studies of animal physiology accomplished by early investigators such as Françoise Magendie and Claude Bernard provided an environment conducive to the creation of similar laboratories for the study of pharmacological phenomena.
One of the first laboratories devoted almost exclusively to drug research was established in Dorpat, Estonia, in the late 1840s by Rudolph Bucheim (18201879) (Fig. 1.1). The laboratory, built in Bucheim's home, was devoted to studying the actions of agents such as cathartics, alcohol, chloroform, anthelmintics, and heavy metals. Bucheim believed that "the investigation of drugs ... is a task for a pharmacologist and not for a chemist or pharmacist, who until now have been expected to do this."
Although the availability of a laboratory devoted to pharmacological investigations was important, much more was required to raise this discipline to the same prominent position occupied by other basic sciences; this included the creation of chairs in pharmacology at other
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