Pharmacology

PHARMACOLOGY (from the Greek pharmakon - medicine, poison, and logos - word, doctrine), the science of the action of medicinal substances on a living organism. The very word pharmacology first appeared in the 17th century; in 1693, Dale entitled his work on pharmacognosy «Pharmacologia, s. manuductio ad materiam medicam». Only almost a hundred years later did Gren publish (in 1790) a textbook on medicinal substances with the doctrine of their therapeutic and physiological action under the title Handbuch der Pharmacologie. Experimental pharmacology developed initially thanks to the works of physiologists (Claude Bernard, Stannius, Schiff, and others); the first school of pharmacologists arose headed by Buchheim, who in 1847 created the first pharmacological laboratory at the University of Dorpat. The experimental method of investigating the action of medicinal substances consists in studying their effect on healthy animals, their systems, and individual organs; research is also frequently performed on unicellular organisms such as infusoria, fungi, and bacteria; plants also often serve as experimental material. After studying pharmacodynamics on healthy animals, the investigation of agents is continued on sick animals, since the susceptibility of healthy and sick organisms is often dissimilar. With this order of investigation, it is often possible to outline the basis for the therapeutic use of a medicine, thanks to which the suitability, value, and possible methods of application of the studied substance in a patient are further clarified. The final stage of the experimental study of a substance takes place in clinics, where the therapeutic action of the medicinal substance is determined with all its features and side effects. Medicinal substances that have been used for a long time are investigated according to the same plan, insofar as it is required to establish the mechanism of their action, their fate in the organism, the sites of their deposition within it, excretion pathways, cumulative or synergistic influence, and the like, under the condition of a morbid state of the organism. The subject of pharmacological research can also be substances that are not used in therapy, but deserve attention, for example, due to their toxicity. In its content, pharmacology is subdivided into so-called general pharmacology and special pharmacology. The content of general pharmacology serves, besides defining the subject and tasks of pharmacology, to establish the boundaries of pharmacology among the disciplines studying various properties of medicinal substances, to elucidate the essence of local and general, respectively resorptive, action of medicinal or poisonous substances on the organism, reflex, elective or specific action, to elucidate the various phases of action and various conditions on the part of the organism and on the part of the medicinal substance that influence the manifestation of the action of medicines or poisons, taking into account the character of their action, routes of administration, distribution in the organism, and pathways of excretion from the organism, as well as those changes that the medicines or poisons themselves undergo in the organism. Thus, questions of general toxicology also find a place in the section of general pharmacology. Special pharmacology studies individual medicinal substances with respect to their action on the whole organism and its systems, on animal organs in situ, on isolated organs, on metabolism, on temperature; it also studies all the questions indicated in general pharmacology, but with respect to each medicinal (respectively poisonous) substance. Pharmacological study captures the life of an animal under conditions of 1) the initial action of the medicine—physiological action; further 2) the developed action of the medicine, but still within the boundaries of a more or less healthy state of the organism; such an effect approaches the action of a medicine used in so-called average therapeutic doses; in both cases, the phenomena that have arisen from the influence of the medicinal substance are characterized by their reversibility; finally, the medicine is studied under conditions when its action disturbs the usual state of equilibrium and signs of toxic action appear; the reaction may still be reversible in these cases as well, but not always; 3) when the organism dies from changes that have occurred under the influence of the introduced substance (lethal doses)—an irreversible reaction. Aid measures for a patient poisoned by a medicine are also developed by pharmacology. Special pharmacology establishes the principles of indications for the therapeutic prescription of a medicinal substance, as well as contraindications under certain conditions on the part of the patient, and is in the closest connection with physiology and physiological chemistry, utilizing both their methodology and all results and conclusions. Pharmacology studies the action of medicines on the diseased organism as well, therefore the connection of pharmacology with pathological physiology also appears completely natural, especially since the most diverse pathological phenomena in the organism can also be caused by medicines. In turn, pharmacology contributes to the successes and development of the indicated disciplines, serving them with its data on medicinal and poisonous substances used to study various physiological and pathological functions and processes. Bacteriology and microbiology, apart from their contact with pharmacology on problems of a general biological character, work together on questions concerning the pharmacodynamic properties of therapeutic sera, the action of toxins and endotoxins, preventive sera, antiseptic and disinfecting substances, and others. Morphological medical sciences, headed by microscopic anatomy, also bilaterally serve the needs of each other with pharmacology; the former provide pharmacology with the material substrate upon which the action of medicines and poisons is studied, while the latter comes to the aid of the former through its research not only in determining the dynamic significance of the studied apparatuses, but also their morphological structure (Lavrentiev). Pharmacology owes its development and successes also to chemistry and physics, with which its connection is growing ever stronger and serves as the foundation for the further progress of pharmacological knowledge. The teachings of physical and colloidal chemistry most fundamentally influence the solution of problems of a pharmacological character concerning the intimate side of the action of medicinal substances on the cell and on the organism as a whole, the distribution of medicinal substances in the organism and the points of application of the action of poisons, the conditions of action of medicines in the organism, changes in the blood and tissues, and so forth. The development of chemistry, and in particular pharmaceutical chemistry with its methods of the synthetic production of medicinal substances, helped solve the question, outlined as early as Buchheim, concerning the dependence of the action of medicines and poisons on their physicochemical properties and made it possible to establish the principle of similarity of pharmacological action in chemically related bodies. The diverse centuries-old use of medicinal agents for therapeutic purposes has bound pharmacology with all types of therapy. Pharmacology, serving clinics, in its turn strives to subject all newest remedies, as well as new information about substances already in use, to clinical analysis. The adjacency of pharmacology with forensic medicine is established through the branch of pharmacology known as toxicology. The latter has recently acquired great significance, especially in the USSR, where the matter of eliminating hazards affecting the health and labor productivity of workers has been set forth in its entire breadth. Therefore, sanitation and hygiene with all their sub-departments, in particular occupational hygiene and nutritional hygiene, having closely taken up the study of the pharmacodynamics of many substances whose action can adversely affect the health of workers under certain conditions of production or nutrition, or the consumption of prepared articles, work hand in hand with pharmacology. Pharmacology is in particularly close contact with pharmaceutical chemistry, pharmaceutical prescription writing, and through the latter with the technology of medicinal preparations and forms; the data of these disciplines are to a significant extent developed by pharmacology as well. Modern pharmacology concentrates its attention on the following tasks: 1) to find and reduce into a single whole those principal regularities that will make it possible to determine the character and direction of the action of medicines on the organism; 2) to study the transformation of medicinal agents in the organism of animals, in particular in humans, the sites of distribution in the organism, the pathways of excretion, and the action of both the introduced substance and its transformation products in the organism, in connection with the study of the environment in which the medicinal substance acts.

The most important specific problems in this aspect are the following: 1) the problem of the action of heavy metals in connection with the electrolytic dissociation of their compounds; 2) the question of pharmacological irritants in connection with the issues of isoinonia and isotonicity of the environment surrounding the cell; 3) the problem of anesthesia in connection with works on agents for inhalation, intravenous, and rectal anesthesia; 4) the question of hypnotics; 5) poisons of the autonomic nervous system with sympathicotropic and parasympathicotropic action; 6) the study of digitalis, ergot, and other plant preparations; 7) the synergistic action of substances and the correlation in action between simple mixtures and compounds; 8) phenomena of habituation to certain drugs or poisons; 9) the question of potential poisons; 10) the study of the strength, speed, and duration of action of medicinal agents; 11) the development of the problem of the correlation between chemical structure and pharmacological action of medicinal and poisonous substances; 12) the study of natural camphor (obtained from various plants) and synthetic camphor; 13) the problem of the penetration and circulation of iodine in the organism and its action on metabolism, nutrition, and tissue structure; 14) the problem of the use of medicinal agents for prophylactic purposes; 15) the study of the action of medicinal substances introduced into the organism in minimal quantities; 16) the action of medicinal substances depending on their dosage form; 17) problems of hormone therapy, organotherapy, lysatotherapy, proteinotherapy; 18) the problem of studying folk medicine remedies. Methods. Pharmacology, as a science adjoining the cycle of biological disciplines, uses all the methods of experimental physiology, analytical, biological, and colloidal chemistry, microchemistry, and the method of biological analysis, in many cases adapting and specializing them to such an extent that essentially one or another method becomes firmly established as part of pharmacology. The method of isolated organs in relation to the liver, kidneys, and heart, introduced by physiologists and elaborated by Kravkov and his disciples on the heart, liver, ear, and other parts of the organism, is generally considered part of pharmacology insofar as the methodology is applied to the study of medicinal and poisonous substances. Having ascertained the quality and intensity of the pharmacological action of a medicinal agent, it is subsequently subjected to clinical testing and application. The history of the pharmacological experimental method also knows so-called therapeutic methods, which include: 1) the most ancient therapeutic method—the empirical, crudely experimental method, which provided a vast amount of material on drugs that was not illuminated by scientific theory; 2) the statistical method; applied with all the rigor of scientific criticism, it becomes a necessary and strict judge of modern experimental methods of laboratory and clinical research on medicinal agents; 3) the symptomatic method, consisting in the registration of observations on the elimination or alleviation of specific distressing symptoms of diseases with the help of medicinal agents, while the main cause and essence of the disease remains ignored; 4) the method of suggestion, when the action of a drug is viewed not as the result of the influence of certain material forces, but as a means of influencing the psyche of the patient; therefore, the taste of the drug, its smell, especially the novelty of the preparation and the novelty of the method of application are highly valued in the method of suggestion. While the experimental method of studying medicinal substances has been particularly cultivated in Germany since the 1840s, French scientists focused the study of medicinal substances in clinics, using predominantly therapeutic methods for this purpose. Thus, two main pharmacological schools were created; specialists in England and Italy adhered to the French school, while scientists of other European countries, in particular Russians who usually received and supplemented their specialized education in Germany, adhered to the German school. The development of pharmacodynamics in laboratories was so successful that the German school of pharmacologists transferred the entire doctrine of the action of medicinal substances into the laboratory, concentrating the study of medicinal agents solely on animals; in the 1860s, German pharmacologists even expressed the opinion that pharmacology has no business whether the studied substance will be used in clinics, and that only the physiological action exerted by the studied substance on the organism is important. This is the view of pharmacophysiologists. Present-day scientific pharmacology is far from such a view. At present, the French pharmacological school under the direction of Tiffeneau, Fourneau, and Florence has also significantly deepened its research on medicinal substances by studying them using the experimental laboratory method on animals, while at the same time conducting the usual therapeutic methods of study on the same agents. A shift toward the clinical examination of medicinal substances in the German school was outlined in the 1870s when Schmiedeberg, together with the clinician Naunyn, organized a pharmacological journal that accommodated articles with clinical analyses of the influence of medicinal substances; in the second decade of the present century, represented by G. Meyer (Vienna), the German school raised the question of the necessity of attaching clinical departments to pharmacological institutes to study the pharmacodynamic properties of medicinal substances in all the diversity of their action on humans. After that, Heubner (Göttingen, Berlin) organized joint teaching with a therapist at the university on certain issues of drug action. Bornstein (Hamburg) systematically investigated the action of drugs in parallel in the laboratory on animals and in the clinic on humans. In Russia, Bogoslovsky (Moscow) as early as the 1890s arranged the teaching of pharmacology in such a way that students saw the action of drugs not only on animals, but also on patients in the clinic. Kravkov followed this same path in his research. The Department of Pharmacology of the 1st Moscow Medical Institute (Nikolaev) raised the question of the necessity of reforming the teaching of pharmacology in the direction of parallel study by students of medicinal substances in the laboratory on animals and in the clinic on humans. The newest medicinal substances produced by Soviet pharmaceutical industry are studied experimentally in the pharmacological laboratory and in clinics on patients and only after such testing are recommended for medical use. The most prominent therapists (Pletnev) speak in favor of the timeliness of the experimental study of drugs on humans as well, and not only on animals. In Italy, where the direction of the French school previously predominated in pharmacology, subsequently under the influence of the German school, which trained a large number of modern Italian pharmacologists (Baldoni, Cervello), the doctrine of drug action strongly deflected toward laboratory research. In England, Cushny combined experimental and therapeutic methods in the study of medicinal substances and managed to turn English pharmacology onto this combined path. The Japanese school of pharmacologists headed by Morishima and Hayashi, students of the German experimental school, works using both experimental-laboratory and clinical-therapeutic methods. American pharmacologists work in this same direction. In the USSR, Kravkov created a prominent Leningrad school of pharmacologists, now headed by Likhachev. The Kazan school (Dogel), Tomsk school (Burzhinsky), and Moscow school (Chervinsky) are not rich in students; the first and last are experimental-physiological in character, while the second is experimental with a clinical bias. Pharmacology is currently studied in Western Europe in special pharmacological institutes attached to universities. Pharmacological institutes in Freiburg (Baden), Munich, Bonn, and Düsseldorf are beautifully arranged and equipped. Some occupy separate buildings of 3 to 4 floors. The institutes contain departments: experimental-vivisection, chemical, in some places bacteriological; a library, museum, material room, photo laboratory; an auditorium, separate rooms for the work of the professor, assistants, and medical specialists; some institutes have rooms for practical classes of students, a room for experimental animals, a room with reduced temperature. A vivarium is arranged at the institute in a special room with departments for various animals; an animal run; an icehouse, a basement. In Italy, there are experimental pharmacological institutes, but there are also institutes of a mixed type—institutes of pharmacology with toxicology and institutes of pharmacology with pharmacognosy (Materia medica). In America, there are pharmacological departments, laboratories, departments of Materia medica and Therapeutics. Japan has special pharmacological institutes of the German type in all universities. In the USSR, pharmacological institutes are housed in the same building with institutes of other departments. Institutes and laboratories have demonstration collections of pharmacological and pharmacognostic material, drawings and tables produced in accordance with the taught course. Older institutes and laboratories have their own libraries. In the USSR, pharmacologists are not united into a separate society, but are members of the All-Union Society of Physiologists, Biochemists, Pharmacologists, and Histologists, in the congresses of which they take part, forming a separate section. Pharmacologists of the USSR also take part in regional congresses of physiologists, pharmacologists, and biologists convened in the Volga region and very regularly in the south in the republics of Transcaucasia and the Caucasus; the last congress was in Erivan in October 1934. Soviet pharmacologists do not have a separate printed organ; in the Physiological Journal of the USSR, they...

Sechenov pharmacology has its own department. The teaching of pharmacology developed in most states under the predominant influence of the German school and consists of a lecture course accompanied by demonstrations of the action of drugs on animals (Austria, Switzerland, Poland, Czechoslovakia, Norway, the Baltic states, partly Italy, Japan); in other countries, the French system of clinical study of drugs is practiced; England, Italy, and America have transitioned to a mixed system of laboratory and clinical methods. The USSR follows the model of the German school. The teaching of experimental pharmacology in our country began in the sixties with Sokolovsky's course in Kazan. Prior to that, materia medica was taught at the Department of Medical Materia Medica, Pharmacy, and Medical Literature in accordance with the pharmacognostic and therapeutic content of Materia medica compendiums and consisted of describing preparations from the pharmacognostic side and indicating their therapeutic use. According to the University Statute of 1863, two departments were created on the medical faculties instead of one: one—«Pharmacognosy and Pharmacy», and the other—«Theoretical and Experimental Pharmacology». Since 1884, the Department of Pharmacology was obliged to teach not only «pharmacology», but also «prescription writing, toxicology, and the doctrine of mineral waters»; pharmacy and pharmacognosy were taught in the 2nd year for 6 hours a week for two semesters, and pharmacology in the 3rd year for 6 hours a week, also for two semesters. Teaching was conducted by the lecture method with demonstrations of experiments and preparations during the lecture. Practical exercises in pharmacology were organized in exceptional cases (Likhachev, Boldyrev, Nikolaev). During the reorganization of all teaching in the USSR, the Department of Pharmacy and Pharmacognosy was liquidated at the medical faculties in 1923, and the Department of Pharmacology was tasked with including in the pharmacology course, along with prescription writing, information on pharmacognosy and pharmaceutical chemistry necessary for mastering pharmacology and skillfully dispensing medicinal agents. For the teaching of pharmacology, 5 hours a week were allotted in both semesters of the 3rd year. Mandatory practical exercises were introduced in 1926. Starting in the autumn of 1934, 150 hours were allocated for pharmacology in the 3rd year across two semesters; under the new plan, another 22 hours were added, which must be considered sufficient for the teaching of pharmacology. By introducing mandatory practical exercises in pharmacology for students, our teaching compares favorably with that abroad.