What Is Anesthetic Gel?

Anesthetic Pharmacology is a branch of pharmacology, which mainly clarifies the rules and mechanisms of interactions between commonly used drugs and the body during the practice of anesthesia. Anesthesia pharmacology is closely related to the practice of clinical anesthesia. The main teaching purpose is to provide the necessary basic theory for the study of clinical disciplines, to guide the rational use of drugs, to formulate medication plans, and to lay the foundation for clinical anesthesia.

Anaesthesiology I. Disciplinary status of anesthesia pharmacology

Anesthesia pharmacology highlights the application of drugs in clinical anesthesia based on the professional characteristics of anesthesia disciplines, focusing on general anesthesia, local anesthesia, muscle relaxants, controlled antihypertensive drugs and blood volume expansion drugs. It is an important basic course for the professional course of anesthesiology. At the same time, anesthesia pharmacology is a medical bridge course, not only the link between pharmacy and medicine, but also the bridge between basic medicine and clinical medicine. A thorough and thorough understanding of the contents of the anesthesia pharmacology course will help medical students in anesthesia to use drugs scientifically, reasonably, and effectively in future clinical work ^[2] .

Narcotic Pharmacy 2. A Brief History of the Development of Anesthetic Pharmacology

Anesthetic pharmacology, like neuropharmacology and cardiovascular pharmacology, is a branch of pharmacology and is the pharmacology of commonly used anesthetic drugs (general anesthesia, local anesthesia, muscle relaxation, analgesics, and other anesthetic aids).

In ancient China, "ma boiling powder" and mandala, aconite, naoyanghua, jasmine root, etc., were anesthetized with wine. Ancient Western Europe was also anesthetized with poppy, mandala, mandraglia, and alcohol. But these anesthesia effects are not sure and unsafe. It was not until the success of ether anesthesia in 1846 that the prologue of modern anesthesia was opened.

In 1956, halothane was used in clinical practice, because of its strong anesthesia effect, rapid induction, rapid awakening, and non-flammable explosion, it quickly replaced ether and became popular for decades. Subsequently, modern fluorinated anesthetics such as triflurane (discontinued), enflurane, isoflurane, sevoflurane, and desflurane came out one after another, becoming the mainstream of inhaled anesthetics. In recent years, xenon anesthesia has been tried again.

In 1970, the medical staff of Xuzhou Medical College took the lead in performing "traditional Chinese medicine anesthesia", which was first taken orally with traditional Chinese medicine decoction. After further research, it was found that the main drug was Yangjinhua. From the traditional Chinese medicine decoction to venous anesthesia (total alkali) intravenous anesthesia, and then to scopolamine intravenous anesthesia.

In 1872 Gre opened the precedent of intravenous anesthetics with chloral hydrate. Helmut Weese reported thousands of cases of phenobarbital intravenous anesthesia in 1932. In 1934, thiopental sodium appeared. Pul'an was used clinically in 1956, followed by sodium oxybate (1956), ketamine (1962), etomidate (1973), and propofol (1977).

Cocaine (1884) was the earliest local anesthetic for clinical anesthesia, and the synthesis of procaine (1905) laid the foundation for local anesthetics. Tetracaine (1930), lidocaine (1944), bupivacaine (1960), and ropivacaine (1988) have come out one after another and have become the most commonly used local anesthetics.

In 1935 King isolated triclosporine chloride from quiz poison. Griffiths used it as a muscle relaxant in the clinic in 1942. In 1951, Theolaff used succinylcholine in the clinic and became a representative of depolarizing muscle relaxants. Subsequently, non-depolarized muscle relaxants such as pancuronium, atracurium, vecuronium, and rocuronium gradually became the protagonists of muscle relaxants.

However, since the application of ether for more than 100 years, anesthesia pharmacology has not been able to form an independent discipline, and most of the knowledge of anesthesia pharmacology is in the works of anesthesia. Until nearly 30 years ago, no monographs on anesthetics were published abroad.

Few domestic pharmacologists have studied anesthesia pharmacology. Wu Yan, Ding Guangsheng and Ai Shixun were the first generation of clinical anesthesiologists in China, and they are also famous pharmacologists. They were selected by the Kuomintang government to study clinical anesthesia in the United States in 1947 with the funds of Gengzi's compensation. Mr. Ding Guangsheng is the only well-known pharmacologist and editor. In addition, Professor Sheng Baoheng has also done systematic experimental studies on the toxicity of local anesthetics.

In 1985, Xuzhou Medical College took the lead in launching an undergraduate major in anesthesiology, established the first domestic anesthesia pharmacology teaching and research department, and published a lecture on "anaesthetic pharmacology" edited by Dai Tijun (internal printing). As more and more colleges and universities of anesthesiology have been set up in the country, the national anesthesiology professional trial textbook "Anesthesia Pharmacology" has been formally published (edited by Zheng Siju and Duan Shiming, China Medical Science and Technology Press, 1990). After several years of trial, in 1996, Shanghai Science and Technology Literature Publishing House published "Dan Shiming and Zheng Siju, editor of" Anesthetic and Pharmacology ". In 2000, anesthesia professional textbooks (a set of 7 volumes), including "Anesthesiology" edited by Professor Duan Shiming, were listed by the Ministry of Education as "course materials for the 21st century" and published by the People's Medical Publishing House. Subsequently, the second edition (edited by Dai Tijun) and the third edition (edited by Dai Tijun and Yu Tian) were published. In 2006, the People's Medical Publishing House published the "Anesthesia Pharmacology Practice Guidance and Exercises" edited by Dai Tijun, which subsequently developed into "Experimental Anesthesia Function", which was rated as the Excellent Teaching Material of Jiangsu Province in 2011. In 2009, the People's Medical Publishing House published "Pharmacology" edited by Professor Dai Tijun for the specialty of nursing anesthesia. These textbooks have made great contributions to the cultivation of talents in anesthesiology and the development of anesthesiology. So far, there are more than 60 institutions in China that have opened anesthesia majors. In addition to undergraduate students, a large number of doctoral and graduate students have been recruited.

In order to lead pharmacologists to intervene in anesthesia and pharmacology research, the Anesthesia and Pharmacology Professional Committee of the Chinese Pharmacological Society was established in 2010. Professor Dai Tijun of Xuzhou Medical College served as the first chairman and was re-elected in 2014.

Since the establishment of the Professional Committee of Anesthesiology of the Chinese Pharmacological Society, it has actively carried out activities and held a national academic conference once a year. In April 2015, he also hosted the "2015 International Forum on Anesthesia and Neuroscience"; he edited the "Concise Pharmacology", which integrates general pharmacology and anesthesia pharmacology, and published the "Advances in Anesthesia Pharmacology" in 2012, 2014, and 2015. "Practical Anesthetic Pharmacology" and "Experimental Methodology of Anesthetic Pharmacology".

Research progress in anesthesia pharmacology

Anesthetic medicine (1) general anesthetic

Inhalation anesthetic

At present, the most widely used is sevoflurane, followed by isoflurane, enflurane, and nitrous oxide. The remaining applications are few or eliminated.

Mechanism of action: It has not been clarified so far. In the 170 years since the advent of ether, people have conducted a lot of research and put forward more than a hundred kinds of hypotheses. Among them, the more important are the "lipid-soluble (lipid) theory", "thermodynamic activity theory", "critical volume theory", "phase transfer chemistry theory" "," Synaptic doctrine, "" protein doctrine, "and more. At present, most scholars believe that "anaesthesia" is multi-effect, multi-mechanism, multi-site and multi-target. That is, "anaesthesia" includes many effects such as analgesia, muscle relaxation, hypnosis, loss of consciousness, cognitive impairment, and suppression of abnormal stress responses; the mechanisms of each effect can be different, so there is no so-called "anaesthesia" receptor; "anaesthesia" both There are specific mechanisms such as receptors, as well as non-specific mechanisms such as lipid theory; general anesthetics affect the central nervous system from the brain to the spinal cord, peripheral nerves and muscles, and other parts; involving cell membrane lipids, receptors, ion channels, Multiple targets such as vectors and transporters.

Route of administration: Traditional inhalation anesthetics are administered through the respiratory tract, but people are also exploring other routes, such as injection and intranasal administration. Krantz et al., In 1962, dissolved methoxyflurane in monoglycerides, etc., and injected them to rabbits, dogs and monkeys. Dai Tijun and others directly injected rabbits and mice with volatile anesthetics (diethyl ether, halothane, enflurane, and methoxyflurane) stock solutions to determine the ED50 and LD50 of sc, ip, im, and iv, and confirmed the inhalation anesthetic. It can be administered by injection. Liu Jingen is an emulsified isoflurane, which has been approved by the China Food and Drug Administration for clinical trials. Sevoflurane is also made into microemulsions.

Other effects: People have begun to pay attention to the effects of inhaled anesthetics on breathing, circulation, development and old age, and to protect the organs.

2. Intravenous anesthetic

At present, the most widely used is propofol, followed by etomidate and ketamine, and the rest such as thiopental and sodium hydroxybutyrate are rarely used or have been eliminated. The mechanism of action of intravenous anesthetics is also unclear. It is only known that ketamine is a non-competitive blocker of N-methyl-D-aspartate (NMDA) receptors, and its anesthetic effect is related to blocking of NMDA receptors. In order to reduce irritation, both propofol and etomidate were modified. Water-soluble etomidate has been formulated as an emulsion. Propofol, which is poorly soluble in water, is an emulsion with many disadvantages. Its water-soluble "prodrug" fospropofol has been registered in the United States. In addition, intravenous anesthesia also uses target-controlled infusions.

Anesthetic Medicine (2) Local Anesthetic

Local anesthetics currently in use are lidocaine, ropivacaine, levobupivacaine, procaine, chloroprocaine, tetracaine, and bupivacaine. The mechanism of local anesthetic is believed to be that the local anesthetic blocks the inner side of the voltage-gated sodium channel of the neuronal cell membrane, and the target is the amino acid residue on the S6 segment of the D4 region of the alpha subunit of the sodium channel. Sheng Baoheng and others proposed through systematic experiments that the treatment of local anesthetic poisoning should not only prevent convulsions, but also maintain circulatory function.

Anesthetic medicine (three) muscle relaxants

It is believed that the ideal muscle relaxant should be non-depolarized, so it is widely used in clinical practice and has become the mainstream. Only succincholine is used as a depolarizing muscle relaxant because of its rapid and short-acting effects. Depolarizing muscle relaxants are known as N2 choline receptor agonists, but their mechanism of action has not yet been elucidated. Depolarizing muscle relaxants still lack satisfactory and effective antagonists. In addition to traditional anticholinergic drugs, non-depolarizing muscle relaxants can also be antagonized with Sugammadex. Sugammadex (Org25969) is a modified -cyclodextrin with a three-dimensional structure like a hollow ring barrel. It forms a 1: 1 relatively strong complex with steroid non-depolarizing muscle relaxants such as 4 positively charged nitrogens of rocuronium, relying on van der Waals force and hydrogen bonding, thereby antagonizing steroid non-depolarizing muscle relaxants It has no significant effect on benzisoquinoline muscle relaxants and depolarizing muscle relaxants.

Anesthetics (4) Analgesics

At present, the most widely used analgesics in clinical anesthesia are fentanyl and its derivatives-sufentanil, alfentanil and remifentanil. They are both mu opioid receptor agonists. Alfentanil has an analgesic intensity of 1/4 and a duration of 1/3. Sufentanil has a strong affinity for opioid receptors, so its analgesic effect is the strongest, 5-10 times that of fentanyl, and its duration is twice that of fentanyl. The potency of remifentanil is similar to that of fentanyl. It works quickly after injection and disappears quickly. It is a true ultra-short-acting opioid. Its structure has an ester bond, which can be rapidly hydrolyzed by non-specific cholinesterase. Regardless of the length of the intravenous infusion, the time for its blood concentration to be halved (that is, the context-sensitive half-time) is always 4 minutes. Within, it is more suitable for intravenous infusion for surgery.

Anesthetic medicine (5) blood volume expansion drugs

Synthetic colloid fluids include hydroxyethyl starch, dextran, gelatin and fluorocarbons. Hydroxyethyl starch (HES) appeared in the 1970s. Although it was developed late, it has developed rapidly. The first generation is hydroxyethyl starch with high molecular weight and high substitution grade; the second generation is with hydroxyethyl starch with medium and medium substitution grade; and the third generation is with hydroxyethyl starch with medium and low substitution grade. Gelatin preparations are chemically synthesized plasma volume expansion drugs using refined animal skin glue or bone glue as raw materials. The gelatin preparations currently used in clinical practice are mainly urea-crosslinked gelatin and denatured liquid gelatin (succinyl gelatin). Dextran was used clinically in the 1940s. Due to the advantages of long expansion time, improved microcirculation, and suppression of postoperative venous thrombosis, it has been used as the preferred colloidal solution for the initial treatment of shock. However, with the advent of HES and denatured gelatin, coupled with dextran having a significant effect on coagulation function, and the potential allergic reaction of dextran-hemibodies, the clinical application of dextran is limited. At present, the commonly used clinical preparations are medium-molecular dextran and low-molecular dextran. Clark and Gollan experiments in 1966 proved that spontaneous breathing mice can be submerged in perfluorinated liquid under normal pressure to survive, thus creating perfluorocarbon compounds as breathing gas. Vector biomedical research. Perfluorocarbons (PFC or perfluorochemicals, PFCS) are compounds produced by replacing all hydrogen atoms in hydrocarbons with fluorine atoms. The diameter is less than 0.2 m. It is an inert substance that is insoluble in water and has very chemical properties. Stable, non-toxic, no metabolic transformation occurs in the body.

There are two main types of fluorocarbon emulsions currently used: Fluosol-DA (20%) and Fluosol-43. The oxygen-carrying capacity of PFC mainly comes from physical dissolution, and it follows Henry's law, that is, the oxygen partial pressure and the oxygen content have a linear relationship. As the oxygen partial pressure changes, the fluorocarbon can dissolve or release oxygen. Because the oxygen-carrying capacity of PFC is not strong, it must be inhaled with a high concentration of oxygen to achieve the best effect.

2 Anesthetic medicine (6) 2 adrenergic receptor agonist

Clonidine is an agonist of the 2 adrenergic receptor. Its receptor selectivity (2: 1,) is 220: 1. It can relieve pain, sedation, antihypertensive, anti-anxiety, stabilize hemodynamics, and inhibit. Digestive tract function and enhance the effect of anesthetics. However, there is no commercial injection in China.

Dexmedetomidine (DEX) is a dextro isomer of medetomidine, an 2 receptor agonist, a receptor selectivity (2: 1,) of 1620: 1, and a receptor affinity of cola It is 7-8 times higher than that of clonidine and its intrinsic activity is stronger than clonidine. The drug has been produced and widely used in China, and has few adverse reactions. It is suitable for tracheal intubation and sedation of patients using ventilator during intensive care treatment. At the same time, due to the characteristics of "wakeable sedatives", DEX has gradually become an adjuvant and sedative for neurosurgical anesthesia and critical care units.

Anesthesia (seven) other

Because it is difficult for a single drug to complete anesthesia for major surgery, multiple anesthesia is used clinically, which makes the problem of drug interaction more prominent. In this regard, anesthesia pharmacologists have carried out a lot of basic and clinical research, put forward the definition of "synergy", "antagonism" and so on, and need to be unified and suggested, and put forward the proposed formula for combined drug quantitative analysis. In addition, there have been many advances in controlled antihypertensive drugs, surgical pain, neuropathic pain, and cognitive dysfunction ^[3] .

Development prospects of anesthetic pharmacology

Anesthesia pharmacology is a young subject with many gaps. Since current anesthesia pharmacology research is mainly anesthesia workers, it is imperative to mobilize more pharmacology workers to participate in anesthesia pharmacology research. Those who have a stable research direction can study the role and mechanism of anesthetic drugs in this direction. It is recommended to carry out systematic and comprehensive pharmacological research on commonly used anesthetic drugs, and to clarify their spectrum of action, characteristics, indications, adverse reactions and pharmacokinetics. Since inhaled anesthetics can also be administered by injection, this should not be difficult. There are many effects of narcotic drugs and there must be more uses. The research results are of great significance for enriching pharmacology and expanding the indications of narcotic drugs. In addition to working closely with anesthesiologists, the research on the mechanism of general anesthetics also requires cooperation with neuroscientists, imaging scientists, biophysicists, computer experts, and pharmacists. It is believed that through the intervention of a large number of pharmacologists, the development of anesthesia pharmacology will be greatly promoted, and Chinese anesthesia pharmacology with Chinese characteristics will stand proudly ^[3] !