How Do I Get Started in Pharmacology Research?

A pharmacological nature and task. ^[1] The concept of drugs; the relationship and differences between drugs and poisons. Pharmacological definition. Pharmacology means the study of the rule and mechanism of mutual interaction between drug and body. The concept and content of pharmacodynamics. Pharmacodynamics describes the mechanism of actions of drug on body. The concept and content of pharmacokinetics. Pharmacokinetics describes the process and rule of drug disposition, it means the action of body on drug, Including absorption, distribution, metabolism and excretion of drugs. Disciplinary tasks of pharmacology. Second, the history of development of drugs and pharmacology. ^[1] The accumulation and spread of ancient drug knowledge. Contributions of Shennong's Compendium of Materia Medica and Compendium of Materia Medica to world medicine. The emergence and development of Western medicine and experimental pharmacology in the 18th century. The emergence of receptor theory and its contribution to the development of pharmacology. Research, development and contribution of pharmacology in modern China. Progress, development direction and future prospects of pharmacology research. Three new drug development and research ^[1] New drug development is a strict and complex process. Source of new drugs and method of selecting topics. Three processes of new drug research. Pharmacological research is the core content of new drug research. New drug approval, production, sales and after-sales investigation.

General Pharmacology

One

Pharmacology (pharmacology) is one of the disciplines that study medicines. It is a basic medical discipline that provides basic theories for the rational use of drugs in the prevention and treatment of diseases. Pharmacology studies the rules and principles of the interaction between drugs and the body (including pathogens). Drugs refer to substances used to prevent and diagnose diseases. In theory, any chemical substance that can affect the physiological functions of the body's organs and / or cell metabolic activities belongs to the category of drugs, including contraceptives and health care drugs. Pharmacology on the one hand studies how the body's cell function changes under the influence of drugs, and on the other hand studies the process of the drug itself in the body, that is, how the body processes the drug. The former is called pharmacodynamics, or pharmacodynamics for short ; The latter is called pharmacokinetics (pharmacokinetics), referred to as pharmacokinetics. It can be seen that the main object of pharmacological research is the body, which belongs to the broad category of physiological sciences. It is significantly different from the pharmaceutical sciences that mainly study the medicine itself, such as biopharmaceuticals, medicinal chemistry, pharmacy, and pharmaceutical sciences. Pharmacology is based on physiology, biochemistry, pathology, etc., and provides a theoretical basis for guiding the rational use of medicine in clinical disciplines. The discipline tasks of pharmacology are to provide experimental data for elucidating the mechanism of drug action, improving drug quality, improving drug efficacy, developing new drugs, discovering new uses of drugs, and exploring the physiological, biochemical, and pathological processes of cells. The pharmacological method is experimental, that is, to observe the laws of action of drugs on the body or its components and analyze the objective principles of action under strictly controlled conditions. The clinical pharmacology that has been gradually developed in recent years is an applied science that takes clinical patients as the research and service object. Its task is to transform the basic theory of pharmacology into clinical drug technology, that is, to convert pharmacological effects into actual curative effects. It is basic pharmacology. Successor. The main purpose of studying pharmacology is to understand what effect the drug has, its mechanism of action and how to give full play to its clinical effect, and to understand the causal relationship of the drug in the process of exerting its effect in theory and practice.

In ancient times, people learned from life experience that certain natural substances can cure diseases and injuries. This is the origin of medicine. Many of these practical experiences have been passed on to this day, such as drinking analgesics, rhubarb catharsis, hydrating worms, and willow fever. Later in the religious superstition and the struggle against evil, and the feudal king's search for pleasure and longevity, medicine has also developed. But more is the accumulation and spread of folk medicine practical experience into herbal medicine, which has been recorded in China and Egypt, Greece, India, etc. For example, the "Shen Nong's Herbal Classic" in China and Egypt's "Eber" around the first century AD Ebers' Papyrus, etc. Ming Shi Li's "Compendium of Materia Medica" (1596) has made great contributions to the history of drug development. It is a classic work of traditional medicine in China. It has 52 volumes, about 1.9 million words, contains 1,892 kinds of drugs, 1160 frames, and more than 11,000 prescriptions. , Is a must-read book for studying Chinese medicine today, and there are seven language translations spread internationally. After the Western European Renaissance (beginning in the fourteenth century), people's thinking began to get rid of religious restraints, thinking that things have their own causes, as long as they can be recognized by objective observation. Swiss doctor Paracelsus (1493-1541) criticized the ancient Greek doctor Galen's causal idealism, ending the dark age of more than 1,500 years in medical history. Later, British anatomy W. Harvey (1578-1657) discovered blood circulation and opened a new era of experimental pharmacology. Italian physiologist F.

The improvement of people's living standards requires more and better new drugs. The development of pharmaceutical science has provided a theoretical basis and technical conditions for the development of new drugs, and market economy competition has also promoted the rapid development of new drugs. The United States Food and Drug Administration (FDA) has approved more than 20 new drugs each year for nearly a decade. China has introduced many new medicines in recent years, but needs to accelerate innovation. The development of new drugs is a very strict and complex process. Although each drug is different, pharmacological research is an essential and critical step. Clinically effective drugs all have corresponding pharmacological effects, but drugs with positive pharmacological effects are not necessarily clinically effective drugs. For example, antihypertensive drugs can lower blood pressure, but antihypertensive drugs are not all antihypertensive drugs, and they are not necessarily good drugs that can reduce complications and prolong life. Therefore, new drug development research must have a process of gradual selection and elimination. In order to ensure the efficacy and safety of drugs for patients, the development of new drugs not only requires reliable scientific experimental results. Governments of various countries have also formulated regulations for the approval and management of new drug production and marketing, and provide legal protection for people's health and the economic and industrial rights of industry and commerce.

New drug sources include natural products, semi-synthetic and fully synthetic chemicals. In the past, the main method of drug selection was relying on practical experience. Now it is possible to find close relatives for screening based on the plant taxonomy of effective drugs, or to infer from the relationship between the chemical structure of effective drugs and pharmacological activity, to synthesize a series of products, and then perform pharmacological screening. In recent years, DNA genetic recombination technology has been used for the body's anti-disease substances (protein components), that is, specific gene segments of DNA are separated and implanted into rapidly growing bacteria or yeast cells to obtain a large number of required protein drugs. In addition, existing drugs can be chemically modified (semi-synthesized) or their dosage forms can be changed, and drugs with better curative effect, less toxicity, or more convenient application can also be obtained.

The research process of new drugs can be roughly divided into three steps, namely preclinical research, clinical research and after-sales research. Preclinical studies include systematic pharmacological studies with animals and observation of acute and chronic toxicity. For drugs with selective pharmacological effects, it is necessary to determine the absorption, distribution and elimination process of the drug in animals before conducting clinical trials. Preclinical research is to find out the spectrum of action and possible toxicity of fresheners. Clinical trials can only be conducted after preliminary approval by the drug administration. The purpose is to ensure medication safety.

In clinical research, 10 to 30 normal adult volunteers first observed the tolerance of the new drug and found a safe dose. Then select patients with specific indications by random grouping, set up double-controls with known effective drugs and blank placebos (no blank controls that harm the patient's health should be used for critically ill patients), and try to use double-blind method (patients and medical staff Neither can distinguish the treatment drug or control drug) observation, and then perform statistical analysis of treatment results to objectively judge the efficacy. At the same time, pharmacokinetic data needs to be calculated by monitoring blood concentration (see Chapter 3 for details). The number of tested cases should generally not be less than 300, and it can be expanded to more than three medical units for multi-center collaborative research in a hospital. For those new drugs that require long-term medication, there should be an observation record of 50 to 100 patients accumulating medication for six months to one year. Based on this, indications, contraindications, dosage courses, and possible adverse reactions are formulated, and then approved by the drug administration department before production and marketing.

Postmarketing survey (postmarketingsurveillance) refers to the social examination and evaluation of new drugs after they are marketed, and focuses on understanding the adverse reactions and long-term effects (including ineffective cases) that occur after long-term use in a wide range of popularization applications. Drugs can only rely on a large number of users (physicians and patients) to make correct historical evaluations.