What is Pharmacology?

Pharmacology is a science that studies the interaction between drugs and the body and the mechanism of drug action, mainly including pharmacodynamics and pharmacokinetics. The former is to clarify the effects and principles of drugs on the body, and the latter to clarify the processes of absorption, distribution, biotransformation and excretion of drugs in the body, as well as the laws of drug effects and blood drug concentrations over time. ^[1]

Chinese name: Pharmacology
Foreign name: pharmacology

Pinyin: yào l xué
Research object: poison

Pharmacological task

The discipline task of pharmacology is to provide theoretical basis for elucidating the role and mechanism of drugs, improving drug quality, improving drug efficacy, and preventing adverse reactions; research and develop new drugs, discover new uses of drugs, and provide experimental data for exploring cell physiology, biochemistry and pathological processes . 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. 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.

Pharmacology Three tasks in pharmacology, or three categories:

First, pharmacology is a compulsory course for medical schools to guide clinical medication.

Second, assessing the efficacy of the drug and how it is economically different from other aspects.

Third, pharmacology is an important part of life sciences.

There are two aspects to this:

On the one hand, in addition to guiding clinical use of drugs, there are also tool drugs, which are further used for research, which greatly promotes academic development;

On the other hand, drug research itself is an important part of life sciences. In this regard, I think from the proportion of Nobel winners, Nobel winners account for more than 30% of pharmacology or drug recipients, which shows that pharmacology plays an important role in life sciences. For example, the discovery of pharmacology in the 1950s and 1990s has greatly improved humankind, and it has also made great progress in science.

Pharmacology research content

Pharmacology is the bridge between basic medicine and clinical medicine, and medicine and pharmacy. Clinical practice is conducted under the guidance of pharmacological science theory, and pharmacological theory is enriched on the basis of experimental research. In addition to respecting scientific laws, the research and application of drugs must also comply with laws, regulations and relevant guiding principles to protect people's lives and health.

The contents of pharmacological research include:

1. Pharmacodynamics: Pharmacodynamics for short. Investigate the effects of drugs on the body, including the effects and effects of drugs, mechanism of action, and clinical applications.

2. Pharmacokinetics: Pharmacokinetics for short. To study the changes and laws of drugs under the action of the body, including the absorption, distribution, metabolism and excretion of drugs in the body, especially the changes in blood drug concentration over time, and factors that affect the efficacy of drugs. ^[2]

A brief history of pharmacological development

Early experience accumulation

The "Shen Nong's Materia Medica" in the first century AD contained 365 drugs.

The "Revised Compendium of Materia Medica" in the Tang Dynasty was China's first Pharmacopoeia, which contained 884 drugs.

The Compendium of Materia Medica by Li Shizhen of the Ming Dynasty is a scientific masterpiece that lasted 27 years, with 1.9 million words in total, 52 volumes, containing 1,892 medicines, more than 11,000 prescriptions, and 1160 illustrations. Widely spread worldwide, it is a glorious page in the history of drug development.

Development of related disciplines

Extraction of natural pharmaceutical active ingredients: such as morphine, quinine, atropine, imidin, shining, cocaine, etc. Advances in chemistry and physiology led to the birth of pharmacology. R. Buchheim founded the discipline of pharmacology and became the first professor of pharmacology in the world. |

Pharmacology and related disciplines infiltrate, learn from each other and promote each other, and many branch disciplines have been derived.

Development history

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 Dynasty

Li Shizhen'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. The book has 52 volumes, about 1.9 million words, contains 1892 kinds of drugs, 1160 frames of illustrations, and more than 11,000 prescriptions. Research on Traditional Chinese Medicine

Pharmacology Of the must-read books in seven languages. 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.

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. After

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 surveillance refers to the social inspection 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 reviews.

Pharmacological status

Definition of new drug: refers to a drug whose chemical structure, drug composition or pharmacological effect is different from existing drugs. The research process of new drugs can be roughly divided into three stages: pre-clinical research, clinical research and post-marketing surveillance. Preclinical research consists of two parts: medicinal chemistry and pharmacology. The former includes the pharmaceutical preparation process route, physical and chemical properties, and quality control standards. The latter includes compliance with the Regulations on the Management of Laboratory Animals (1998, Ministry of Science and Technology of the People's Republic of China) The pharmacodynamics, pharmacokinetics and toxicology of the experimental animals as research objects are aimed at ensuring the safety, effectiveness and control of medication. Preclinical pharmacology research is an insurmountable bridge stage in the entire new drug evaluation system project, and the conclusions it has are of great value for the transition of new drugs from experimental research to clinical application. Clinical studies of new drugs are generally divided into four phases. The phase clinical trial is a preliminary clinical pharmacology and human safety evaluation test on normal adult volunteers. It is the initial stage of human trials of new drugs and provides scientific basis for subsequent research. Stage I was open, 20 to 30 cases, and the dose was explored. The phase II clinical trial is a randomized double-blind controlled clinical trial with the objective of selecting the best clinical application scheme. Phase II: blind, random, 100 pairs. The phase III clinical trial is an expanded multi-center clinical trial before the new drug is approved for marketing and during trial production. The purpose is to conduct a social review of the effectiveness and safety of the new drug. After the new drug passes this phase of clinical trials, it can be approved for production and marketing. Stage III: blind, random, 300 cases. Phase IV clinical trials are safety and effectiveness evaluations of new drugs tested in a wide range of social populations after they are launched on the market. The efficacy and adverse reactions are examined under conditions of widespread and long-term use. This phase is important for eventually establishing the clinical value of new drugs significance. Stage IV: Open,> 2000 cases.

Clinical Pharmacology

The two sister disciplines of clinical pharmacology and clinical pharmacy are new disciplines emerging in the 1960s. The penetration between marginal disciplines is particularly prominent among them, making it difficult for medical workers to distinguish between them. Although both belong to the field of pharmacy, each has its own research purpose and focus.

concept

Clinical pharmacology is a discipline that studies the interaction between drugs and the human body. It is both the last comprehensive stage in pharmacological research and a new branch of pharmacology. The main feature that distinguishes it from basic pharmacological research is that clinical pharmacological research is performed in the human body. Clinical pharmacological research is one of the most important contents in evaluating new drugs.

Early clinical pharmacology can be simply regarded as "testing with the human body". For example, there is a record of "Jun You Sick Drinking Medicine and Trying It First" in our feudal society. Observing the pharmacological effect directly by people abroad is an example of Lind's treatment of crew members with scurvy with lemon orange in 1747. However, clinical pharmacology was officially proposed as a discipline, and it should be counted from 1947. In 1974, Professor Gold of the United States gave a lecture on clinical pharmacology at Cornell University (Cornell University), thus creating a new era of clinical science. In the following 20 years, the number of new drugs increased sharply due to the development of the chemical synthesis industry.

Species differences (including differences between human races and differences between humans and animals) are more important in clinical pharmacology. Species differences make clinical pharmacology not support the introduction of a drug that has passed animal experiments directly into the clinic, even between different races, because of the existence of species differences, it is not appropriate to use the medicine directly on different races . Such as ephedrine's pupil dilatation effect, white people have the strongest pupil dilation effect, followed by yellow people, black people have almost no. In particular, the occurrence of the reaction stop (thalidomide) in West Germany in the 1960s made clinical pharmacology research truly valued by the relevant administrative departments and the medical scientific community in many countries, and therefore established its role in the research of new drugs. Ideal location.

The main tasks of clinical pharmacology research in the evaluation of new drugs

1. Observe the efficacy and toxic side effects of new drugs on humans, and study the transport and transformation of new drugs in humans. This kind of research is carried out under the guidance of experienced clinical pharmacologists only after the state-owned authority approves the state-of-the-art hospitals. In recent years, the widespread application of mathematics, physics, chemistry, and electronics has made pharmacodynamic evaluations (physiological indicators such as ECG, EEG, respiration, etc .; biochemical indicators such as camppg concentration changes, etc.) to a microscopic level. And the application of gas chromatography, high performance liquid chromatography, radioimmunity and other technologies solved the problem of drug microanalysis that could not be solved in the past, and finally obtained a drug body kinetic parameter. In this way, the standards and methods for measuring the quality of medicines are transferred from the human body to the human body. The pharmacodynamics and pharmacokinetic evaluation of new drugs have gone a long way. This task is mainly accomplished through phase to clinical studies.

2. Long-term in-depth clinical observation of the efficacy and toxic and side effects of new drugs is a regular work in clinical pharmacological research. Purposeful, planned, and organized evaluation of the long-term efficacy and adverse effects of a drug in a group of patients is the main form of phase IV clinical research. For example, the American Diabetes Research Group from 1961 to 1966 was able to cooperate with 12 universities to recruit a total of 1027 patients to observe the prevention of vascular comorbidities during the development of diabetes. As a result, it was found that the patients in the mesulfate group had cardiovascular mortality. Significantly higher than the other drug groups, so in 1969 the use of metsulfuron was stopped. FDA in the United States has a special drug use experience department responsible for collecting reports of adverse reactions to new drugs on the market (including the spontaneous reports of medical personnel in various places). Scattered reports of adverse reactions to certain medicines occasionally experienced by many clinicians and pharmacists in China. Compared with developed countries, such an organized and large-scale phase IV clinical study is still far away.

Difference from related science

The main differences between clinical pharmacology and clinical pharmacy

(I) Research objects In recent years, China's work in these two fields has been actively carried out. Because the research object is people, especially the evaluation of new drugs should be cautious.

(2) If the research scope of clinical pharmacology is purely a new drug evaluation, it will undoubtedly be the scope of clinical pharmacology. But the new use of old medicine and the discussion of the mechanism of traditional Chinese medicine, such as the study of prostaglandin levels in the amniotic fluid of Lifanuo during labor induction; the comparison of 17-hydroxycorticosteroids in urine of tripterygium for rheumatoid arthritis; the old medicine phenytoin sodium The determination of pharmacokinetic parameters of normal healthy people in China, digoxin, gentamicin, etc. should be the content of clinical pharmacology. Because it is an evaluation of old drugs, trials do not need to be approved by the authority, but some trials are not thorough enough from the report chapter. For example, there is no routine physical examination and necessary laboratory tests and dietary instructions for normal health.

(3) Scope of clinical pharmacy The discussion of clinical pharmacy centered on rational drug use is very lively and the content is quite extensive. Such as prescription analysis; summary of rational drug use; pharmacist in-depth clinical and doctor-like similar drug regimen; acting as a drug consultation; pharmacokinetic test, etc.

(IV) Differences between the two As far as pharmacokinetic tests are concerned, the main differences between clinical pharmacology and clinical pharmacology are generally considered to be that the main test subjects before were normal healthy people, and every drug marketed for systemic use should have a pharmacological agent. Kinetic data (a comprehensive partial pharmacokinetic analysis has been done for hundreds of drugs abroad, which is still lacking in China). The latter test subjects are patients, especially those with poor liver and kidney function. The tested drugs are mainly limited to a few drugs with low therapeutic index and non-linear kinetic characteristics, which eliminate the constant dose-related drugs in the body.

Major functions of clinical pharmacology staff

(1) Responsible for conducting clinical pharmacology research of new drugs The clinical pharmacology base of the Ministry of Health must actively undertake the clinical pharmacology research of a drug, and it is technically responsible to guide and assist clinical hospitals in various regions to develop and do clinical trials and verification of new drugs. And is responsible for formulating clinical research plans, organizing clinical trials, and jointly with the provinces, autonomous regions, municipalities, and designated hospitals to complete the clinical research tasks of new drugs approved by the Ministry of Health or provincial, autonomous regions, and municipalities. After the clinical study is completed, a scientific summary report is written and sent to the development unit and copied to the Ministry of Health and the relevant provincial, autonomous region, and municipal health departments and bureaus.

(2) Clinical re-evaluation of produced drugs. Each clinical pharmacological base should actively carry out re-evaluation of listed drugs for certain types of drugs undertaken. Drugs that are harmful to people's health due to uncertain effects, adverse reactions, or other reasons should be sanitary. Ministry of Planning, conducting social surveys based on the actual situation of the unit, collecting data, combining experimental research, analysis and adjustment, and drawing scientific conclusions. Submit evaluation opinions to the Ministry of Health, the Department of Health and the Bureau.

(3) Responsible for drafting clinical trial indicators and evaluation principles for various drugs. Each clinical pharmacological base is responsible for drafting requirements, content and observation indicators for clinical trials and clinical validation of various drugs, and the principles of clinical evaluation to achieve the clinical research of various drugs. Standardized requirements.

(4) To guide the rational use of drugs in clinical monitoring of adverse drug reactions and improve the level of drug treatment. When conducting clinical pharmacology research, each clinical base should accumulate experience in the safe and effective use of new and old drugs, conduct scientific summary at any time, carry out tasks such as epidemiological studies of adverse drug reactions and investigation of drug abuse, and have the responsibility to guide doctors Reasonable medication.

(V) Training on clinical pharmacology for doctors conducting clinical research on new drugs. Beijing Medical University, Shanghai Medical University, and Sun Yat-sen Medical University have three clinical training doctors at the clinical bases of the Ministry of Health and train provinces, autonomous regions, and municipalities to designate new drug clinical conditions. Doctors in the test hospitals hold training courses at least once a year, and can also organize small training courses in different specialties. Other clinical pharmacological bases can also gradually create conditions and run training courses for local clinical pharmacological backbones. The bases can communicate horizontally and communicate with each other, and gradually write a unified national clinical pharmacology handout, so as to continuously improve the level of training and work for the construction of a clinical pharmacology team in China.

(6) Carrying out professional consultation on clinical pharmacology and exchange of information and intelligence Each clinical pharmacology base should actively carry out clinical pharmacology consultation, and the units with conditions should be open to society. For drugs with a narrow scope of treatment, blood concentration monitoring should be carried out in this unit to provide scientific basis for clinical treatment and do everything necessary to ensure that the medication is safe and effective. Information exchange between bases is an extremely important means to promote the development of clinical pharmacology.

(7) Undertake temporary tasks and temporary clinical pharmacological tasks assigned by the Ministry of Health and the Department of Health.

New Pharmacology

A new drug refers to a drug whose chemical structure, drug composition, or pharmacological effect differs from existing drugs. China's "Drug Administration Law" stipulates that new drugs refer to drugs that have not been produced in China; changing the dosage form, changing the route of administration, adding new indications, or making new compound preparations of already produced drugs is also within the scope of new drugs.

Pharmacology

The research and development of new drugs is a systematic project with high scientific and technological content, multiple investments, long cycles, high risks and high benefits. It is also a very rigorous and complex process, and each medicine is different. Therefore, pharmacological research is an essential key step. Constantly discovering and providing new drugs that are safe, efficient, adaptive to the disease spectrum, and of controllable quality are of great significance for protecting people's health and developing the national economy.

From discovery to production to clinical application, new drugs generally go through the innovation and development stages. In the innovation stage, effective components for synthesis or separation of purified products should be formulated and screened on pathological models to find compounds that have development value, that is, lead compounds. Then study the structure-activity relationship of the lead compound, and carry out technological research, preparation research, quality control, pharmacodynamic evaluation, safety evaluation, clinical pharmacological research, etc. according to the relevant regulations of the state on the approval of new drugs.

New drugs can be discovered through synthesis and screening under the guidance of practical experience or theory. The research process of new drugs can be roughly divided into preclinical research, clinical research and post-marketing surveillance. The pre-clinical research mainly includes medicinal chemistry research and pharmacological research. The former includes the drug preparation process route, physical and chemical properties, and quality control standards, while the latter is based on experimental animals that comply with the "Regulations on the Management of Experimental Animals". Science, pharmacokinetics and toxicology research. The clinical study is divided into four phases:

Phase I clinical trials are preliminary pharmacological and human safety tests performed on 20 to 30 normal adult volunteers. They are the initial stage of human trials of new drugs and provide a scientific basis for subsequent research.

The phase II clinical trial is a randomized double-blind controlled trial, with no less than 100 cases observed, mainly to make a preliminary evaluation of the effectiveness and safety of the new drug, and to recommend a clinical dose.

The phase III clinical trial is an expanded multi-center clinical trial before the new drug is approved for marketing and during trial production. The number of cases observed is no less than 300. The effectiveness and safety of the new drug are socially investigated. Can be approved for production and marketing.

Phase IV clinical trials are safety and effectiveness evaluations of new drugs that continue to be carried out in a wide range of social populations after the drug is marketed. They are used to investigate efficacy and adverse reactions under conditions of long-term widespread use. This period is of great significance for the final determination of the clinical value of new drugs.

At present, the concept of phase 0 clinical trials is proposed in the research and development field. Phase 0 clinical trial is a kind of research limited to traditional phase I clinical trials, which aims to evaluate the pharmacodynamics and pharmacokinetic characteristics of the tested drugs. The characteristics are: small dose, short cycle, small number of subjects, not for the purpose of drug efficacy evaluation, the purpose is to pharmacodynamics and pharmacokinetics of antitumor candidate drugs acting on target indicators and / or biomarkers Learn to evaluate. ^[2]

Chinese Pharmacology

Traditional Chinese medicine pharmacology is a science based on the basic theories of traditional Chinese medicine, using pharmacological methods to study the effects of traditional Chinese medicine on various functions of the body and its working principles. Focus on the achievements of modern scientific research on traditional Chinese medicine related to the theory of traditional Chinese medicine. Through research and experiments, understand the outline of traditional Chinese medicine pharmacology research. The research purpose of traditional Chinese medicine pharmacology is mainly to enable medical workers to further understand the working principle of traditional Chinese medicine in preventing and treating diseases and the material basis for producing curative effects. It is an important component in the field of Chinese medicine. The main tasks are as follows:

Pharmacology (1) Through experimental research, to clarify the action properties and active strength of traditional Chinese medicine, which will help clarify the theory of Chinese medicine

(2) Combining the theory of traditional Chinese medicine with the results of modern scientific research can help promote the development of traditional Chinese medicine.

(3) The method of experimental pharmacology combined with the separation and extraction of the effective ingredients of traditional Chinese medicine is used to provide scientific experimental basis for further research on the compatibility and application of traditional Chinese medicine, improvement of dosage forms, improvement of efficacy, and reduction of toxicity.

(4) Through experimental pharmacological methods, develop new Chinese herbal medicines with medicinal value, expand medicine sources, and use old medicines for new uses.

A brief history of the development of traditional Chinese medicine and the main achievements of modern research: (1) The brief history of the development of traditional Chinese medicine and the major works of Materia Medica The emergence and development of traditional Chinese medicine were produced and developed in the process of the working people in the struggle against nature. China's first monograph on pharmacology, "Shen Nong's Materia Medica", is a summary of drug knowledge obtained by working people in the practice of natural struggle and production struggle. Among them, ephedra for asthma, Changshan antimalarial, deworming for worms, and rhubarb diarrhea are all valuable scientific records.

With the development of human society, the application of folk medicine has become increasingly widespread. During the Han and Jin dynasties, Hua Ying, Li Dangzhi, Wu Pu and others all contributed greatly to drugs. At the beginning of the sixth century AD, Liang. Tao Hongjing collected the popular "Best Doctors" and the Compendium of Materia Medica at the time, compiled and compiled the Compendium of Compendium of Materia Medica, and received 73O kinds of medicines, which not only increased the variety of drugs, but also according to the natural characteristics of jade, grass, wood, insects and beasts, fruits and vegetables, rice Source classification has created a natural taxonomy of herbal medicines, which has been followed by herbal medicines such as "Compendium of Herbs" and "Compendium of Materia Medica". It also has a column for "common medicines for various diseases", which is very convenient for dialectical use. The book makes a series of explanations on the season of medicine collection, storage, custody, authenticity and identification, processing methods, pharmaceutical specifications, and medication methods, which have played a role in the history of medicine.

In the seventh century AD, there were nearly thirty books on Compendium of Materia Medica, with some repetitions in the writing style and content materials. There were also shortcomings in the rules and explanations, and they needed to be improved. So Don. More than 20 people including Su Jing and Li Yan compiled 844 kinds of medicines contained in the "Revised Compendium of Materia Medica", and collected drawings of medicinal specimens from various parts of the country. They were promulgated in 654 AD, also known as "Tang Materia Medica". The Pharmacopoeia promulgated by the government is 877 years earlier than the "New Zealand Pharmacopoeia", and it can also be said to be the earliest Pharmacopoeia in the world, which has a great impact on domestic and foreign countries.

During the Northern Song Dynasty, more attention was paid to the reorganization of ancient medical books, and the "Kaibao Detailed Draft Materia Medica" and the "Kaibao Redact Materia Medica" have been compiled. During Jiayou's years, he was in charge of various "Yuyou Supplementary Materia Medica" edited by Yu Xi, and Su Song edited the "Book of Sketches". Tang Shenwei compiled the large-scale comprehensive pharmacology book "The Classics" based on these two books and referring to other medical books. "Her Materia Medica in the Prestige of History and Evidence" has been valued by doctors of all generations since then. The Song Dynasty has been revised several times by the state, and has continued to present the "Comprehensive Materia Medica of the Classics of History and Classics" and "Alternative Materia Medica of the Classics of History and Newly Revised Classics of History and Classics." The book of medicinal herbs, which was completed before the Song of the Ministry of Songs, preserves the essence of many ancient masterpieces and retains the original appearance of the early literature. It is a large-scale medicinal herb that has been popular before the introduction of Materia Medica, and has been used as a model for the study of Materia Medica. Some of the ancient medical books cited in the book have been lost, and the outline can still be gleaned from the book, so it has not only great practical value, but also important historical documentary significance.

In the Ming Dynasty, Liu Wentai and others were ordered to compile the Essentials of Compendium of Materia Medica, based on concise and concise materials. This is the second cursive book compiled by the government after the New Revised Materia Medica. Later, Li Shizhen published a large number of books on herbal medicine in the five hundred years after the "Compendium of Materia Medica", and a large number of practical drugs emerged.

There are new developments, combined with his rich practical experience in drug collection, identification, pharmacy and drug use, which is based on the "Materia Medica Materia Medica" and references to nearly 800 books from hundreds of classics in the history of the field; field investigations and identification Authenticity, compiled into "Compendium of Materia Medica" 52 volumes, divided into 16 sections, 62 categories, received 1,892 kinds of medicine, 1120 pictures. Carved in Jinling in early 1590. This book summarizes the achievements of Chinese Materia Medica before the 16th century. It has been engraved many times in the 300 years since its publication. It has English, Japanese, German, French, Russian and other translations. After the publication of the Compendium of Materia Medica, Qing Dynasty scholars wrote compendium of Compendium of Materia Medica based on it from different perspectives, such as supplementing and correcting the Compendium of Compendium of Materia Medica, deleting the simplified Compendium of Compendium of Materia Medica and compiling compendium of Materia Medica ", As well as clinical practical small herbal medicine" Compendium of Materia Medica "," Compendium of Materia Medica "and so on. Particularly worth mentioning is that the author of Wu Qiao's "Plant Names and Realities Examination" based on the real object, finely painted the medicinal drawings, is clear and realistic, and corrects the errors of ancient sketches. The "Long Editor" section excerpts from ancient herbal and historical books The relevant records in the study have great reference value and are generally valued by scholars at home and abroad.

After the liberation, the government was very concerned about the cause of Chinese medicine, and promulgated Chinese medicine policies, established Chinese medicine research institutions, and opened Chinese medicine colleges. With the vigorous development of the Chinese medicine industry, a large amount of data has been accumulated in the resources investigation, variety identification, chemical and pharmacological research, and clinical observation of traditional Chinese medicine. The Ministry of Health of the People's Republic of China has compiled and promulgated the Pharmacopoeia of the People's Republic of China, which has clearly stipulated the specifications, efficacy, indications, dosage usage and quality control of traditional Chinese medicine. Many books on traditional Chinese medicine, such as Traditional Chinese Medicine, Identification of Traditional Chinese Medicine, Traditional Chinese Medicine Chemistry, and Clinical Traditional Chinese Medicine, etc. have made preliminary conclusions from different aspects. Also published large-scale comprehensive medicine books, such as "Chinese Medicine Journal", "National Compendium of Chinese Herbal Medicine" and "Chinese Traditional Medicine Dictionary", etc., which comprehensively and systematically summarized the achievements of traditional Chinese medicine research, and the latter also extracted ancient Chinese herbal medicine literature, which is a study of traditional Chinese medicine. Important reference book.

(2) The main achievements of Chinese medicine pharmacology research in recent years have been using modern scientific methods to study Chinese medicine for more than 80 years. In the early 1920s, Chinese scholars first conducted systematic chemical and pharmacological research on ephedrine, pseudoephedrine, and ephedrine, the components of ephedra. Due to the discovery of its specific pharmacological effects, its thesis report not only shocked the country, but also received great attention from abroad, and aroused world scholars' interest in ephedrine and other traditional Chinese medicine research, making ephedrine an important drug worldwide. Due to the social turmoil, uneasy war, rudimentary equipment, and very few personnel, research was slow and results were scarce. The research on this single drug was mainly conducted without the cooperation of chemistry, pharmacology and clinical. In terms of chemistry, researches on dozens of medicinal materials, such as Yanhusuo, Uncaria, Ephedra, Changshan and Fangji. Pharmacology mainly researched dozens of medicinal materials, such as ephedra, coptis chinensis, Changshan, Yanhusuo, and crane grass. After liberation, the government attached great importance to the research and development of TCM and TCM, and put forward important instructions for inheriting, developing, sorting out and improving TCM, and established TCM research institutions and TCM hospitals at all levels from central to local provinces and cities to make TCM Pharmacology and clinical research have entered a new stage. The research scope has developed from a single party to a compound prescription, and research topics have ranged from resource investigation to biopharmaceutical identification, processing, chemistry,

Pharmacology

From pharmacology to the clinic, the variety of single-flavor drugs and the wide range of research are unprecedented. Research on Yanhusuo, Fanfang, Ginseng, Coptis chinensis, Pueraria lobata, Chuanxiong, Salvia miltiorrhiza, Panax notoginseng, Fructus Aurantii, Fructus Aurantii, Rhizoma Curcuma, Rhubarb, Rhubarb, Artemisia annua, Greenwood, Leonurus, Trichosanthin, etc. , Anti-parasites, anti-tumor, antipyretic, analgesic, heart-strengthening, diuretic, anti-hypertensive, anti-arrhythmic, etc., a large number of screening. Not only has more research been done on traditional Chinese medicine, but also many herbs, such as andrographis, evergreen, hair holly, dwarf tea, fushou grass, Manshanhong, etc., and has provided clinical applications, greatly enriching the variety of drugs. Comprehensive research on pharmacological studies of Chinese herbal medicine, part of which clarified the theory of traditional Chinese medicine (such as promoting blood circulation, stasis, etc.), and clarified the active ingredients of some traditional Chinese medicine (such as fumarate, artemisinin, ligustrazine, etc.) , Improved certain dosage forms (such as cold granules, Shengmai injection, etc.), and found new uses of certain medicines (such as Zhishi, Qingpi, Heliconia bud, etc.). However, the composition of traditional Chinese medicine is complex and its effects are multi-faceted. One ingredient must not represent a blind taste of Chinese medicine, and a certain effect cannot summarize its full efficacy. Therefore, many problems of traditional Chinese medicine need further study. Questions need further study.

Basic Pharmacology

Pharmacological effect

1. Drug action refers to the initial action between the drug and the body's cells. It is the cause, the molecular reaction mechanism, and its specificity.

2. Pharmacological effects The result of drug action is the performance of the body's response, and it has selectivity to different organs. The most basic pharmacological effects include excitement and inhibition.

3. The selectivity of pharmacological effects, that is, the specificity of pharmacological effects, is the scope of the effects of drugs on the body. It is the basis for drug classification and the basis for guiding medication and formulating therapeutic doses when clinical medication is used. The selectivity of a drug is related to the chemical structure of the drug itself.

4. The drug effect is dual.

(1) Therapeutic effect: refers to the effect caused by drugs that is consistent with the purpose of medication.

(2) Adverse reactions: Those reactions that do not meet the purpose of drug treatment and cause pain or harm to patients.

Therapeutic effects of drugs

1. Definition Any effect that meets the purpose of medication or achieves the effect of prevention and treatment is called therapeutic effect.

2. The classification is divided into:

(1) Cause-based treatment: The treatment for the cause is called the cause-based treatment, also called the root cause. The purpose of medication is to eliminate the primary pathogenic factors and completely cure the disease.

(2) Symptomatic treatment: use drugs to improve the symptoms of the disease, but the cause cannot be eliminated. The purpose of medication is to improve symptoms.

Adverse drug reactions

Reactions that do not meet the purpose of the drug treatment and cause illness or harm to the patient are called adverse reactions. It is generally predictable, and can recover on its own after stopping the drug.

Pharmacology

1. Side-effect drugs that are not related to the purpose of treatment at the therapeutic dose are generally not serious and difficult to avoid.

2. Toxic reactions The serious adverse reactions caused by excessive doses of drugs or long-term medications and excessive accumulation of drugs in the body are generally serious and can be predicted and avoided. Divided into:

(1) Acute toxicity: immediate toxicity caused by overdose in a short period of time.

(2) Chronic toxicity: Toxicity that gradually accumulates in the body after long-term use. Carcinogenic, teratogenic and mutagenic triple reactions also belong to the category of chronic toxicity.

3. Sequelae effect refers to the residual biological effect when the blood drug concentration has dropped below the threshold concentration after drug withdrawal.

4. Withdrawal response The exacerbation of the original disease after sudden withdrawal, which is called a rebound reaction.

5. Allergic reactions (allergic reactions) are immunopathological reactions caused by drugs.

6. Specific Heterogeneous Reactions Some medicines cause specific adverse reactions in a small number of patients, which is a genetic biochemical defect.

7. Secondary reaction The small favorable reaction caused by the drug treatment effect, also known as treatment contradiction.

Pharmacological dose-response relationship

Concept of dose

1. The minimum effective amount (threshold dose or threshold concentration) is the minimum dose required for efficacy.

2. The therapeutic amount refers to the commonly used amount of the drug, which is the effective dose range commonly used in clinical practice, and is generally an amount between the minimum effective amount and the extreme amount.

3. The dose that causes the greatest effect without poisoning (that is, the limit of safe use).

4. The commonly used dose is larger than the threshold dose and smaller than the extreme dose. In general, the amount of treatment should not exceed the extreme amount.

5. The minimum poisoning quantity exceeds the extreme quantity, and the quantity that just caused mild poisoning.

6. Half lethal dose (LD50) is the dose that causes half of the animals to die.

Response curve

1. Quantitative changes in the pharmacological effect of the quantity are continuously increased and decreased.

Pharmacology Grade expression, such as blood pressure rise and fall, smooth muscle contraction and so on.

(1) Titer strength: The dose required for a drug to achieve a certain pharmacological effect reflects the affinity of the drug and the receptor. The smaller the value, the greater the strength. It is usually expressed as the dose that produces the 50% maximum effect, and is called the half effective dose (ED50).

(2) Efficacy: the ability of a drug to achieve the maximum pharmacological effect (increasing the concentration or dose without the effect amount continuing to rise), reflecting the intrinsic activity of the drug.

(3) The meanings of the drug's maximum efficacy and effect intensity are completely different, and they are not parallel.

2. The pharmacological effects of qualitative reactions show changes in the nature of the response, which can only be expressed by all or none, positive or negative, such as death and survival, convulsions and non-convulsions.

(3) Time-Effect Relationship of Drugs The process of drug effects changing with time is called the time-effect relationship of drugs. The drug's time course is divided into: incubation period, duration, and residual period.

Drug safety evaluation

1. The ratio of the half lethal dose to the half effective dose of the therapeutic index (LD50 / ED50). The larger the ratio, the greater the relative safety and the smaller the opposite. The drug effect and toxicity of this indicator are not clear, and this safety indicator is not reliable.

2. The safety range is the distance between ED95 and TD5. The larger the value, the safer it is. The safety of a drug is related to the dose (or concentration) of the drug.

3. Safety index LD5 / ED954. Safety limit (LD1-ED99) / ED99.

Mechanisms of action

Pharmacological effects can occur through:

1. Change the physical and chemical properties of the environment around the cell.

2. Replenish various substances that the body lacks.

3. Affects neurotransmitters or hormones.

4. Act on specific target receptors, enzymes, ion channels, vectors, nucleic acids, immune system and genes.

5. Non-specific action Drug action is mainly related to its physical and chemical properties, not dependent on chemical structure, and has no specific action mechanism.

Pharmacology

Receptor theory

(A) the concept and characteristics of the receptor

1. The receptor is a glycoprotein or lipoprotein, which exists in the cell membrane, cytoplasm, or nucleus, and can recognize a certain amount of chemical substances in the surrounding environment, which can be combined with drugs and can transmit information and cause cellular components.

2. Ligands that can specifically bind to receptors are divided into endogenous and exogenous ligands.

3. Receptor characteristics: saturation; high sensitivity; reversibility; high affinity; diversity.

(B) the type of receptor

According to the characteristics of receptor protein structure, information transmission process, effect properties, and receptor location, receptors are divided into four categories:

1. Ion channel receptor.

2. G-protein coupled receptor.

3. Tyrosine kinase receptor.

4. Intracellular receptors.

Pharmacology (Three) the interaction between drugs and receptors

According to the affinity and intrinsic activity of drugs, drugs can be divided into agonists and antagonists.

1. An agonist can bind to a receptor and excite the receptor to produce a corresponding effect. It has affinity and intrinsic activity with the receptor.

(1) Completely agonist: has strong affinity and intrinsic activity ( = 1).

(2) Partial agonists: strong affinity and weak intrinsic activity ( <1) with the receptor.

2. Antagonists can block the ligand of the receptor, and have strong affinity with the receptor, but have no intrinsic activity ( = 0).

(1) Competitive antagonists: they can compete with agonists for the same receptor, bind reversibly to the receptor, and the dose-response curve shifts to the right to the right, with the same slope and height (Emax).

(2) Non-competitive antagonists: do not compete with the agonist for the same receptor, or irreversibly bind to the receptor, the dose-response curve shifts to the right, the slope decreases, and the height (Emax) decreases.

(IV) Signal transduction after the drug interacts with the receptor. The second messenger: After the ligand acts on the receptor, it can induce the production of some intracellular chemicals, which can be used as intracellular signal transmission substances to further transmit the signal to The downstream signal transduction protein is called the second messenger.

Second messengers that have been identified include: cyclophosphoadenosine (cAMP), cyclophosphine guanosine (cGMP), inositol phosphate (IP3), diglycerides (DG), and calcium ions.

Pharmacokinetic

Pharmacokinetics, referred to as pharmacokinetics for short, studies the process of drug in vivo and the laws of drug concentration in the body over time. Although the drug is not necessarily concentrated in the target organ in the body, the pharmacological effect is proportional to the plasma concentration of the drug after the distribution reaches equilibrium. Doctors can use pharmacokinetic laws to scientifically calculate the dose of a drug to achieve the required blood concentration and to grasp the strength of the effect. This can achieve better clinical efficacy than empirical prescription alone.

absorb

A few drugs similar to normal metabolites, such as 5-fluorouracil, methyldopa, etc. are absorbed by the active transport of carriers in cells. This active transport mechanism has a relationship with drug distribution in the body and renal excretion. Closer. Facilitated diffusion (facilitated diffusion) is a means of transport across the membrane along the concentration gradient of the carrier, such as glucose absorption, the absorption rate is faster. Solid drugs cannot be absorbed. Tablets and capsules must be disintegrated and dissolved in the gastrointestinal tract before they can be absorbed.

Drug oxidation process

Drug reduction process

The second step in the biotransformation is binding. Most oxidized drugs are combined with glucuronic acid via the glucuronyl transferase action of liver microsomes. Some drugs can also be combined with acetyl, glycine, sulfuric acid and so on. Donor participation is required for these binding reactions. For example, uracil diphosphate is the donor of glucuronic acid.

Pharmacological properties

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). Drug refers 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.

Pharmacology Including contraceptives and health pills. 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, or pharmacokinetics for short. 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.