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Ministry of Education and Science of Ukraine Ministry of Health Care of Ukraine Sumy State University I. Yu. Vysotsky, R. A. Khramova, A. A. Kachanova PHARMACOLOGY Textbook In two parts Part 1 Recommended by the Academic Council of Sumy State University Sumy Sumy State University 2019 УДК 615(075.8) V99 Reviewers: V. V. Shmanko – Doctor of Medical Sciences, Professor, Head of the Course of Clinical Pharmacology; Department of Pharmacology with a Course of Clinical Pharmacology (I. Horbachevsky Ternopil State Medical University); A. V. Ataman – Doctor of Medical Sciences, Professor, Head of the Department of Physiology and Pathophysiology with a Course of Medical Biology (Sumy State University) Recommended for publication by the Academic Council of Sumy State University as a textbook (minutes № 8 of 21.06.2018) Vysotsky I. Yu. V99 Pharmacology : textbook : іn 2 parts / І. Yu. Vysotsky, R. А. Khramova, A. A. Kachanova. – Sumy : Sumy State University, 2019. – Part 1. – 311 p. ISBN 978-966-657-747-7 ISBN 978-966-657-748-4 (part 1) Material of the textbook is given according to the Training Programme in Pharmacology and Medical Prescription. Questions of general and special pharmacology are described at the up to date level. The textbook contains mechanisms of action, pharmacokinetics, pharmacodynamics, indications and contraindications for clinical use, and side effects of main groups of pharmacological drugs. The main attention is paid to data having fundamental meaning for training future doctors. For students of higher medical educational institutions of the IV level of accreditation. УДК 615(075.8) © Vysotsky І. Yu., Khramova R. А., ISBN 978-966-657-747-7 Kachanova A. A., 2019 ISBN 978-966-657-748-4 (рart 1) © Sumy State University, 2019 INTRODUCTION Presently, a large number of drugs are used to treat and prevent different diseases. Doctor of any speciality should be able to know them well for correct prescribing pharmacotherapy to patients. In this regard, there is a need for quality training of students of higher medical educational institutions in pharmacology, knowledge of which is basic and integrates theoretical and clinical disciplines. Pharmacology finishes theoretical training of future doctors and is a logical continuation of courses of normal and pathological physiology, biochemistry, microbiology, and anatomy. Therefore, the authors, when presenting the material, considered it necessary to briefly recall physiological, biochemical, immunological, and anatomical knowledge that is necessary for understanding of pharmacodynamics of drugs and their mechanisms of action. Suggested textbook contains main rules of drug prescription, data of general and special pharmacology. With the aim to form stable skills in students to work with drug nomenclature, the unified nomenclature system of drugs, based on International Nonproprietary Names (INN), is given in the textbook. This system is used in modern educational literature of different countries. In most cases, the authors indicate both INN and most commonly used trade names of drugs. All chapters of the textbook are given in volume that is necessary for clear understanding of principles of action and effective and safe use of drugs. Each pharmacological group is constructed in a unified and logical sequence which facilitates the perception, assimilation and use of information. Due to large volume of information which should be mastered by students, the authors focus on group properties of drugs and describe the main representatives of groups. At the same time, the same drugs, used for different indications, are described in different chapters (e. g., -adrenergic antagonists are given in chapters “Antiadrenergic drugs”, “Drugs for treatment of hypertension”, “Drugs for treatment of ischemic heart disease”, and “Antiarrhythmic drugs”). Main data about drugs are given in one main chapter, and additional information is given in other chapters. Data about pharmacodynamics, pharmacokinetics, clinical applications, and side effects are given for each group of drugs; and, if it is necessary, corresponding data about individual drugs are additionally given. Suggested textbook contains data about new drugs and modern scientific data. Mechanisms of action and therapeutic indications for drugs are given considering modern data of biochemistry, pathological physiology and fundamental pharmacology. This textbook contains some elements of clinical pharmacology. A separate chapter of the textbook describes general principles of treatment of acute poisoning by drugs and other toxic substances. Measures to prevent the ingress of poison into the body, inactivation of poisons by antidotes, restriction of poisons action by physiological antagonists, acceleration of poison elimination from the body, and resuscitation measures are given in this chapter. Besides, resuscitation measures at cases of inhibited respiration, collapse, acute heart failure, and bronchoconstriction are considered, especially in acute period of poisoning. The textbook is recommended for third-year students of higher medical educational institutions. Its structure and content correspond to the curriculum of pharmacology, approved at an interdepartmental meeting of heads of pharmacological departments of higher medical educational institutions. We will be grateful for any comments and suggestions that may arise from the readers of this textbook. 4 MEDICAL PRESCRIPTION Introduction to Medical Prescription The science about drugs consists of two branches of knowledge: pharmacology and pharmacy. Pharmacology is the science about interaction between an organism and a drug. Pharmacy is the science which studies questions of search, processing, preparation, and standardization of medicines. Pharmacy is complex science which includes pharmacognosy, pharmaceutical chemistry, technology of the medicinal form preparation, and prescription. Prescription is a section of pharmacy, which consists of the prescribing rules and rules of the drug preparations. Accordingly, prescription is divided into pharmaceutical and medical one. Pharmaceutical prescription contains the drug preparation rules. Practically, pharmaceutical prescription is separated in the special sector – medicinal form technology. Medical prescription includes the rules of drug prescribing. Namely, medical prescription has the important role in the physician’s practical activity. Most important terms of medical prescription are the following. Medicinal substance (in Latin – “substantia pharmaceutica”) is one chemical substance or chemical element which is used as the medicinal remedy. Medicinal remedy (in Latin – “medicamentum”) is natural or synthetic substance or mixture of some substances which are permitted by the Ministry of Public Health Services for the treatment and prophylactic of the certain diseases. Pharmacological remedy is substance or mixture of substances with determined pharmacological activity and toxicity which is object for clinical trials. After receiving the sanction for the use in medical practice, the pharmacological remedy is registered in the state register of medications. Medicinal form is the created state of medicinal remedy (remedies) which is appropriate for the practical use and provides the ability to reach the necessary therapeutic effect and drug stability during the storage. In dependence to consistency, there are solid, soft, and liquid medicinal forms. In turn, liquid medicinal forms are divided into forms for external use, forms for internal intake, and injections. 5 The same medicinal remedy may be prescribed in different medicinal forms. A drug (preparatum) is the medicinal remedy in certain medicinal form. Nowadays, the sources of medications are very diverse. They include mineral substances, nonorganic and organic compounds, vegetable raw materials, animal organs, microbial metabolic products, etc. Prior to the use, medicinal raw materials undergo the appropriate processing. Processing may be simple (drying, grinding) or complex (isolation of active substances). Due to complex processing of vegetable raw material, so- called galenic medications or galenic formulations (tinctures, extracts) are derived. Galenic medications are drugs which are derived due to maceration of extraction of medicinal raw materials. Besides active substances, galenic medications contain also ballast substances (cellulose, mucus, proteins, tars, etc.). Therefore, galenic medications are not appropriate for parenteral administration. Besides galenic drugs, pharmaceutical industry produces more purified drugs containing maximum of active substances from herbal raw material and minimum of ballast substances. Such medications are called novogalenic drugs. They are appropriate for parenteral administration. For example, opium is medicinal raw material; opium powder is simple preparation; opium tincture is galenic formulation; omnoponum is novogalenic drug; morphine is pure opium alkaloid which is used for parenteral administration in the form of hydrochloride salt solution. The relationship of different pharmacological terms may be considered by the example of atropine sulfate: – Belladonna – herbal raw material; – alkaloid atropine – medicinal substance; – atropine sulfate – medicinal remedy; – atropine sulfate in powders, in tablets, in ampules, in eye ointment – drugs. All drugs are divided into three groups in dependence to a degree of expressiveness of their action upon an organism. Poisonous drugs (Venena, the list A). Drugs with very high toxicity