What Are the Most Common Uses for Penicillin?

Penicillin (or transliterated penicillin) is also known as penicillin G, peillin G, penicillin, penicillin, penicillin sodium, penicillin sodium, penicillin potassium, and penicillin potassium. Penicillin is a kind of antibiotics. It refers to a class of antibiotics containing penicillin in the molecule, which can destroy the cell wall of bacteria and play a bactericidal role during the reproduction of bacterial cells. It is an antibiotic extracted from penicillium. Penicillin belongs to -lactam antibiotics (-lactams). -lactam antibiotics include penicillin, cephalosporins, carbapenems, monocyclics, cephalosins, etc. Penicillin is a very common antibacterial drug. However, a skin test must be performed before each use to prevent allergies.

Drug Name: Penicillin G
Alias: Penicillin, penicillin sodium, benzyl penicillin sodium
Foreign name: Benzylpenicillin / Penicillin

Whether prescription drugs: prescription
Athletes use with caution: Inadvertent use
discoverer: Alexander Fleming

Introduction to penicillin compounds

Penicillin Basic Information

Chinese name: penicillin

Chinese alias: Penicillin

English name: benzylpenicillin

English alias: cilloral; pradupen; Ursopen; benzyl penicillin; cosmopen;

CAS number: 61-33-6

Molecular formula: C ₁₆ H ₁₈ N ₂ O ₄ S

Molecular weight: 334.39000

Exact mass: 334.09900

PSA: 112.01000

LogP: 1.18960

Physical and chemical properties of penicillin

Density: 1.42g / cm ³

Boiling point: 663.3ºC at 760 mmHg

Flash point: 355ºC

Refractive index: 1.655

Storage conditions: ventilated, low temperature and dry

Penicillin Safety Information

Customs Code: 32041900

WGK Germany: 2

Danger category code: R42 / 43

Safety instructions: S36 / 37

RTECS number: XH9700000

Dangerous goods mark: Xn ^[1]

Penicillin R & D History

Before the 1940s, humans have not been able to grasp a drug that can effectively treat bacterial infections with small side effects. If someone had tuberculosis at that time, it meant that person would soon die. In order to change this situation, researchers have been exploring for a long time, but the breakthrough progress made in this regard has come from an unexpected discovery. ^[3]

In modern times, British bacteriologist Fleming first discovered penicillin, the world's first antibiotic, in 1928. Alexander Fleming discovered penicillin because of a lucky mistake.

In 1928, the British scientist Fleming first discovered penicillin in experimental research, but because the technology was not advanced enough at the time, the understanding was not deep enough, Fleming did not separate penicillin separately.

In 1929, Fleming published his research results. Unfortunately, this paper has not received much attention from the scientific community since its publication.

When looking at the petri dish with a microscope, Fleming found that Staphylococcus colonies around the mold had been lysed. This means that certain secretions of the mold can inhibit staphylococci. Subsequent identification showed that the above-mentioned mold was Penicillium punctatus, so Fleming called the penicillin the antibacterial substance it secreted. Unfortunately, Fleming has not been able to find a method for extracting high-purity penicillin, so he cultured Penicillium sp. Strains from generation to generation, and in 1939 provided the strains to the British pathologist Froth who prepared the system to study penicillin. (Howard Walter Florey) and biochemist Chan. ^[3]

In 1938, the German chemist Ernst Chann saw the Fleming's thesis in an old book pile, and began to conduct purification experiments. ^[3-4]

Florie and Chann re-experimented with penicillin in 1940. They injected 8 mice with a lethal dose of streptococcus, and then treated 4 of them with penicillin. Within a few hours, only those four mice treated with penicillin were still alive. Since then, a series of clinical experiments have confirmed the efficacy of penicillin on various bacterial infections such as streptococcus and diphtheria. The reason penicillin can kill germs without damaging human cells is because the penicillin contained in penicillin can hinder the synthesis of germ cell walls and cause lysis and death of germs, while human and animal cells do not have cell walls.

In the winter of 1940, Qian En refined a little penicillin. Although this was a major breakthrough, it was still far from clinical application. ^[3-4]

In 1941, a baton purified from penicillin was passed to the hands of Australian pathologist Walter Flory. With the assistance of the U.S. military, Flory isolated bacteria from the soil brought back from airports in various countries when pilots went out to perform missions, increasing the production of penicillin from 2 units per cubic centimeter to 40 units. ^[3-4]

Around 1941, Howard Flory, a pathologist at the University of Oxford in the United Kingdom, and biochemist Qian En realized the isolation and purification of penicillin, and found its effect on infectious diseases. However, penicillin can cause allergic reactions in individual people, so it is being applied You must do a skin test before. Most of the antibiotics used are extracted from microbial culture fluids, and some antibiotics have been artificially synthesized. Due to the different chemical composition of different types of antibiotics, their mechanism of action on microorganisms is also very different, some inhibit protein synthesis, some inhibit nucleic acid synthesis, and some inhibit cell wall synthesis. ^[3]

After a period of intense experiments, Flory and Qian En finally extracted penicillin crystals by freeze-drying. Later, Flory found a mold that can be used to extract a large amount of penicillin on a melon, and prepared the corresponding culture solution with corn flour. Driven by these research results, American pharmaceutical companies began mass production of penicillin in 1942.

By 1943, pharmaceutical companies had discovered a way to mass produce penicillin. Britain and the United States were at war with Nazi Germany. This new drug is very effective at controlling wound infections.

In October 1943, Flory signed the first batch of penicillin production contracts with the US military. Penicillin was born at the end of World War II and quickly reversed the war situation of the Allies. After the war, penicillin was widely used, saving tens of millions of lives. By 1944, the supply of medicines was sufficient to treat all the Allied soldiers who fought during World War II. For this great invention, in 1945, Fleming, Flory, and Qian En won the Nobel Prize in Physiology or Medicine for "discovering penicillin and its clinical utility". ^[3-4]

In 1945, the British chemist DCHodgkin used X-ray diffraction to determine the molecular structure of penicillin.

On September 5, 1944, China's first batch of domestic penicillin was born, unveiling the history of antibiotic production in China. As of the end of 2001, China's annual production of penicillin has accounted for 60% of the world's total annual production of penicillin, ranking first in the world. ^[3-4]

In 2002, Birol et al. Proposed a model based on a process mechanism. This process comprehensively considered various physiological changes of microorganisms during fermentation, and found that this was a very complicated process. In order to study the penicillin process more conveniently, Birol extended the non-structured model proposed by Bajpai and Reuss to further simplify the model and facilitate research.

Main functions of penicillin

Penicillin is an important antibiotic with high efficiency, low toxicity and wide clinical application.

World War II poster: Thanks to penicillin, the wounded can go home safely Its successful development has greatly enhanced the ability of humans to resist bacterial infections and led to the birth of the antibiotic family. Its emergence opened a new era in the treatment of diseases with antibiotics. After decades of improvement, penicillin injection and oral penicillin have been able to treat pneumonia, meningitis, endocarditis, diphtheria, and anthrax respectively. Following penicillin, antibiotics such as streptomycin, chloramphenicol, oxytetracycline, and tetracycline have been continuously produced, which has enhanced human's ability to treat infectious diseases. But at the same time, the resistance of some bacteria is gradually increasing. To solve this problem, researchers are currently developing more potent antibiotics, exploring how to prevent bacteria from acquiring resistance genes, and developing antibacterial drugs using plants as raw materials. ^[5]

Penicillin cannot tolerate enzymes produced by drug-resistant strains (such as drug-resistant golden glucose), is easily destroyed by it, and has a narrow antibacterial spectrum, which is mainly effective against Gram-positive bacteria. Penicillin G is divided into potassium salt and sodium salt. The potassium salt can not be directly injected intravenously. The amount of potassium ions must be carefully calculated during intravenous infusion, so as to prevent the injection of hyperkalemia into the human body and inhibit the heart function and cause death. ^[5]

Penicillin antibiotics are very toxic. Because -lactams act on the cell wall of bacteria, and humans have only cell membranes without cell walls, they are less toxic to humans. In addition to causing severe allergic reactions, in general dosage, The toxicity is not obvious. ^[5]

Before using this product, you must first perform an intradermal test. The penicillin allergy test includes a skin test method (referred to as a penicillin skin test) and an in vitro test method, of which intradermal injection is more accurate. The skin test itself is also dangerous. About 25% of patients with anaphylactic shock die from the skin test. Therefore, adequate preparation should be made for skin test or injection. When changing to a different batch of penicillin, a skin test is also required. The dry powder can be stored for many years without failure, but the injection solution and skin test solution are unstable, and it is better to prepare it fresh. And for those excreted from the kidneys and those with poor renal function, the dose should be adjusted appropriately. In addition, topical application has many opportunities for sensitization, and bacteria are prone to drug resistance, so it is not recommended. ^[5]

Classification of penicillin

Penicillin was used in the clinic in the early 1940s. After a lot of research on penicillin, some penicillins were found. When people chemically modified penicillin, some effective semi-synthetic penicillins were obtained. In the 1970s, some were found from microbial metabolites. The mother nucleus is similar to penicillin and also contains a -lactam ring, but does not have a tetrahydrothiazole ring structure, which can be divided into three generations : the first generation penicillin refers to natural penicillin, such as penicillin G (benzyl penicillin); the second generation penicillin It refers to the use of penicillin mother nucleus-6-amino penicillin acid (6-APA) to change the side chain to obtain semi-synthetic penicillin, such as methicillin, carbenicillin, ampicillin; the third generation penicillin is the mother nucleus structure. It has the same -lactam ring as penicillin, but does not have a tetrahydrothiazole ring, such as thiomycin and nocardiomycin. ^[6]

According to its characteristics, it can be divided into:

Penicillin G type: such as penicillin G potassium, penicillin G sodium, long-acting cilin penicillin G, peillin G, penicillin, penicillin, penicillin sodium, benzyl penicillin sodium, penicillin potassium, and penicillin potassium. ^[6]

Penicillin type V : (alias: phenoxymethyl penicillin, 6-phenoxyacetamido penicillin acid) such as penicillin V potassium, etc. (including multiple dosage forms). ^[6]

Enzyme-resistant penicillin: such as oxacillin (Xinqing II), clozacillin and so on. ^[6]

Ampicillin: such as ampicillin and amoxicillin. ^[6]

Anti-Pseudomonas penicillin: such as carbenicillin, piperacillin, ticarcillin and so on.

Mecillin and its esters and piracetin: such as mecillin and its esters and piracetin, which are more resistant to enzymes and effective against certain negative bacilli (such as large intestine, Klebsiella and Salmonella), but effective on difference. ^[6]

Methicillin: such as Tamoxicillin and others ^[6]

Penicillin preparation method

Natural penicillin and semi-synthetic penicillin are produced in completely different ways.

Natural Penicillin

Penicillin G production can be divided into two steps: strain fermentation and extraction and purification. Strain fermentation: Penicillium chrysogenum is inoculated onto a solid medium, and cultured at 25 ° C. for 7 to 10 days to obtain a Penicillium spore culture. The spore suspension was inoculated with sterile water into the sterilized culture medium in the seed tank, passed in sterile air, stirred, and cultured at 27 ° C for 24-28 hours, and then the seed culture solution was inoculated into the fermentation tank. The sterile phenylacetic acid precursor-containing medium was aerated with sterile air, stirred, and cultured at 27 ° C for 7 days. During the fermentation process, phenylacetic acid precursor and appropriate amount of medium need to be added. Extraction and purification: The penicillin fermentation broth is cooled and filtered. The filtrate was subjected to multi-stage countercurrent extraction with butyl acetate in an extractor under the conditions of pH 2 to 2.5 to obtain a butyl ester extract, transferred to a buffer solution of pH 7.0 to 7.2, and then transferred to butyl ester. The butyl ester extract is decolorized by activated carbon, a salt-forming agent is added, and penicillin G potassium salt can be obtained by azeotropic distillation. Penicillin G sodium salt is prepared by penicillin G potassium salt through an ion exchange resin (sodium type). ^[3]

Semi-synthetic penicillin

By using 6APA as an intermediate and a variety of chemically synthesized organic acids for acylation, various types of semi-synthetic penicillin can be prepared.

6APA is obtained by using a penicillin acylase produced by a microorganism to cleave penicillin G or V. The enzyme reaction is generally carried out under the conditions of 40-50 ° C and pH 8-10; the enzyme solid-phase technology has been applied to the production of 6APA, which simplifies the cracking process. 6APA can also be prepared from penicillin G by chemical method, but the cost is higher. The introduction of the side chain is to make the corresponding organic acid into an acid chloride with a chlorinating agent, and then perform an acylation reaction with 6APA in water or an organic solvent according to the stability of the acid chloride, using an inorganic or organic base as a condensation agent. The condensation reaction can also be performed directly in the lysate without the need to isolate 6APA. ^[3]

[Penicillin concentration method]

A method using penicillin to specifically kill wild-type cells and retain auxotrophic cells. Penicillin can inhibit the synthesis of bacterial cell walls, so it can only kill bacteria in growth and reproduction, not bacteria that stop dividing. In a selective liquid medium that can only grow the wild type but not the mutant type, the wild type is killed by penicillin, while the mutant type is not killed, thereby eliminating the wild type and concentrating the mutant type. It is applicable to bacteria and actinomycetes and is one of the common methods for screening auxotrophic mutants. ^[3]

Penicillin Drug Description

Pharmacological effects of penicillin

Penicillin antibiotics are a general term for a large class of antibiotics in -lactams. Because -lactams act on the cell wall of bacteria, while humans have only cell membranes without cell walls, penicillin antibiotics have little toxicity and are the antibiotics with the largest chemotherapy index . However, its common allergic reaction to penicillin antibiotics ranks first among various drugs, with an incidence rate of up to 5% to 10%. It is a skin reaction, manifesting rash, angioedema, and the most severe is anaphylactic shock. Occurs within a few minutes. Symptoms include dyspnea, cyanosis, decreased blood pressure, coma, limb rigidity, and finally convulsions. Delays in rescue can cause death. Various

Penicillin-the discoverer The route of administration or the use of various preparations can cause anaphylactic shock, but the incidence of injection is the highest. The occurrence of allergic reactions is not related to the size of the drug dose. Those who are highly allergic to this product can cause shock even in very small amounts. Injected into the body can cause epileptic seizures. Large doses of long-term injections are toxic to the central nervous system (such as causing convulsions, coma, etc.), and can be restored by stopping or reducing the dose.

Oral administration is easily destroyed by gastric acid and digestive enzymes. After intramuscular or subcutaneous injection, the absorption is faster, and the peak drug concentration is reached in 15-30 minutes. Penicillin has a short half-life in the body and is mainly excreted from the urine in its original form.

Penicillin pharmacological action is to interfere with the synthesis of bacterial cell walls. The structure of penicillin is similar to the D-alanyl-D-alanine in the mucin structure of the cell wall. It can compete with the latter for transpeptidases, hinder the formation of mucin, cause cell wall defects, and cause bacteria to lose cell wall. Penetration barrier, killing bacteria.

Pharmacokinetics of penicillin

Penicillin is not acid-resistant and should not be taken orally. After intramuscular injection, the peak drug concentration (Cmax) is reached within 0.5 hours, which can be widely distributed in tissues and body fluids, and easily penetrate into tissues with inflammation. The concentrations in the chest, abdominal cavity, and joint cavity fluid are about 50% of the serum concentration. This product can pass through the placenta, but it is difficult to penetrate the blood. Cerebrospinal fluid barrier, milk may contain a small amount of penicillin, which is difficult to penetrate into the eyes, bone tissue, non-blood supply area and pus cavity. Plasma protein binding rate is 45% to 65%, blood elimination half-life (t1 / 2) is about 30 minutes, and renal function can be extended to 2.5 to 10 hours, and elderly and newborns can also be extended. About 19% of this product is metabolized in the liver, mainly excreted through renal tubular secretion. Under normal renal function, about 75% of the dose is excreted from the kidney within 6 hours, and a small amount is excreted through the biliary tract. Hemodialysis can remove this product, while peritoneal dialysis cannot. ^[8]

Penicillin combination reaction

The problem of drug abuse in the clinic has caused some adverse reactions, especially the compatibility and application of penicillin with other drugs, and the interactions and adverse reactions generated cannot be ignored.

1. Penicillin cannot be combined with similar antibiotics

Since their antibacterial spectrum and antibacterial mechanism are mostly similar, the combined effects do not add up. Conversely, concomitant medications can aggravate kidney damage and can cause dyspnea or apnea. There is cross-resistance between them, and the combination of two -lactam antibiotics is not advocated.

2. Penicillin cannot be used in combination with sulfa drugs and tetracyclines

Penicillin is a bactericidal agent in the breeding period, which hinders the synthesis of bacterial cell walls. Tetracycline is a bacteriostatic agent, which affects the synthesis of bacterial protein. The combined effect of the two is an antagonism. In general, the drug should not be used in combination. Clinical data show that the antibacterial efficacy of penicillin alone is 90%, the efficacy of sulfa drugs alone is 81%, and the combined antibacterial efficacy of the two drugs is 75%. It can not be used in combination under special circumstances.

3. Penicillin cannot be mixed with aminoglycosides for infusion

Mixing the two is the same as infusion of the infusion set to the patient. Because -lactam of penicillin can inactivate gentamicin, the mechanism is chemical interaction between the two. Therefore, mixed application is strictly prohibited. Penicillin intravenous should be used. Infusion, gentamicin intramuscularly.

In summary, the improper combination of penicillin and the adverse drug reactions due to drug interactions cannot be underestimated. Penicillin is the most commonly used antibiotic for the treatment of various infectious diseases. It is necessary to strictly grasp the indications for drug use, reasonable combination, effective measures, and reduce unnecessary adverse reactions.

Bacteriostatic agents such as chloramphenicol, erythromycin, tetracyclines, and sulfa drugs can interfere with the bactericidal activity of penicillin and should not be combined with penicillins, especially when treating meningitis or severe infections that require rapid sterilization.

probenecid, aspirin, indomethacin, butazone, and sulfa drugs can reduce the excretion of penicillins in the renal tubules, thus increasing the blood concentration of penicillins and maintaining them for a long time. The half-life is prolonged and the toxicity may be increased. .

Penicillin potassium or sodium is contraindicated with heavy metals, especially copper, zinc, and mercury, because the latter can destroy the thiazole oxide ring of penicillin. Rubber tubes or stoppers made of zinc compounds can also affect penicillin activity. Acidic glucose injection or tetracycline injection can destroy the activity of penicillin. Penicillin can also be inactivated as an oxidant or reducing agent or a hydroxy compound.

Intravenous infusion of penicillin added cefotaxime, lincomycin, tetracycline, vancomycin, erythromycin succinate, amphotericin B, norepinephrine, m-hydroxylamine, phenytoin, hydroxazine, prochlorperazine, After promethazine, vitamin B family, vitamin C, etc. will appear cloudy. Therefore, this product should not be co-infused with other drugs.

Paecillin can enhance the effect of warfarin.

After the product is mixed with aminoglycoside antibiotics, the antibacterial activity of the two is obviously weakened, so the two drugs cannot be administered in the same container.

Penicillin drug toxicity

penicillin allergy

It is quickly absorbed after oral administration, and about 75% to 90% can be absorbed from the gastrointestinal tract. The effect of food on drug absorption is not significant. Its protein binding rate is 17% to 20%, and the blood elimination half-decay period (t1 / 2) is From 1 to 1.3 hours, about 24% to 33% of the dose is metabolized in the liver after taking the drug, and 46% to 68% of the dose is excreted from the urine within 6 hours as a prototype drug. Some drugs are excreted through the biliary tract and severe kidney Serum half-life can be extended to 7 hours in patients with dysfunction. Serum dialysis can clear penicillin, while peritoneal dialysis does not clear the product. ^[8]

Penicillin is the least poisonous side effect of various antibiotics, because its mechanism of action is to destroy the cell wall formation process and structure, while the human body does not have a cell wall. Penicillin is basically not pharmacologically toxic to the human body, but large doses of penicillin may also cause neurotoxicity. The main cause of side effects of penicillin is insufficient purification of penicillin, and impurities in it are likely to cause allergies to the human body.

allergic reactions: penicillin allergic reactions are more common, ranking first among various drugs. Severe allergic reactions are anaphylactic shock (type allergy) with an incidence of 0.004% to 0.015%. Type allergies include hemolytic anemia, drug rash, contact dermatitis, interstitial nephritis, asthma attacks, etc., and type allergy The response, that is, the serotype, is also more common, with an incidence rate of 1% to 7%. Those with anaphylactic shock who do not rescue in time have a high mortality rate. Therefore, as soon as it occurs, the patient must be rescued locally. Immediately inject 0.5% to 1ml of 0.1% epinephrine into the patient. If necessary, dilute it with 5% glucose or sodium chloride injection for intravenous injection. If the clinical performance does not improve, repeat it after half an hour. . If the heart is stopped, epinephrine can be injected intracardiacly. At the same time, a large amount of adrenocortical hormones are dripped intravenously, and blood volume is replenished; those with persistently elevated blood pressure are given vasoactive drugs such as dopamine. Antihistamines may also be considered to reduce urticaria. Patients with dyspnea are given oxygen inhalation or artificial respiration, and those with obvious edema of the throat should be tracheotomy in time. The use of penicillinase is of little significance.

Allergy principle

Penicillin is unstable and can be broken down into penicillin thiazolic acid and penicillinic acid. The former can be polymerized into a penicillium thiazolate polymer and combined with a polypeptide or protein to form a penicillium thiazolate protein. It is a fast-acting allergen and the main cause of allergic reactions; the latter can also interact with cysteine in the body. Acid forms a delayed allergen-penicillin, which is associated with serum sickness-like reactions.

Toxicity: Penicillin toxicity is rare, and peripheral neuritis may occur in the intramuscular injection area. Intrathecal injection of more than 20,000 units or intravenous infusion of large doses of penicillin can cause muscle clonus, convulsions, and coma (penicillin encephalopathy). It is more common in infants, elderly and patients with impaired renal function. Penicillin can cause psychotic episodes. Individual patients may experience anxiety, fever, shortness of breath, high blood pressure, fast heart rate, hallucinations, convulsions, and coma after application of procaine penicillin. The mechanism by which this reaction occurs is unknown.

Double infection: Penicillin-resistant Staphylococcus aureus, Gram-negative bacilli, or Candida albicans infections can occur during treatment with penicillin. Candida overproduction can make the tongue coating brown or even black.

Hyperkalemia (hypokalemia) and hypernatremia: When a large amount of penicillin potassium is administered intravenously, hyperkalemia or potassium poisoning can occur. Administration of penicillin sodium in large doses can cause hypernatremia, especially in patients with impaired renal function or cardiac insufficiency. After giving patients 100 million units of penicillin sodium daily, a small number of patients may develop hypokalemia, metabolic alkalosis, and hypernatremia.

Hechsler reaction and contradiction in treatment: Syphilis, leptospirosis, or other infections may be exacerbated when penicillin is used to treat them. It is called the Hirschmann reaction, a systemic reaction caused by the killing of a large number of pathogens. The contradiction of treatment is also seen in patients with syphilis, which is caused by the syphilis lesion disappearing too quickly after treatment, but the tissue repair is slow, or the fibrous tissue shrinks, which hinders organ function.

6. Veterinary clinical allergies are generally mild, mainly manifested as sweating, excitement, restlessness, muscle tremors, dyspnea, increased heart rate, unstable standing, sometimes urticaria, eyelid and facial edema, vulvar and rectal swelling and no Bacterial cellulitis, severe shock or even death.

[ Reason ]

In clinical use, the attack of high temperature, acid and alkali, and heavy metal ions should be avoided. Try to avoid using glucose injection with acidic pH as the solvent, and when using 0.9% sodium chloride as the solvent, you should also use the current preparation, otherwise it will cause the decomposition of penicillin if it is left for too long. Allergic reactions occur.

[ First aid measures ]

Immediately discontinue the medicine, lie on his back, rescue in situ, adopt a low head and high position.

0.5% to 1ml of 0.1% epinephrine hydrochloride is subcutaneously injected, and children can reduce it. 0.5ml of subcutaneous injection can be injected every half an hour until it is out of danger. If necessary, glucocorticoid or antihistamine is added.

(1) Those with cardiac arrest should undergo cardiothoracic compression or intracardiac injection of 0.1% epinephrine hydrochloride 1 ml.

Oxygen inhalation, mouth-to-mouth artificial respiration during respiratory depression, and intramuscular injection of stimulants such as nicoramic acid or sylvia.

Laryngeal edema affects tracheotomy while breathing.

Use hydrocortisone 200 mg, or 5-10 mg of dexamethasone, add 50% Glucose to 40 ml of intravenous injection, or add 5-10% Glucose to 500 ml of intravenous drip.

According to the needs of the disease, vasoactive drugs such as dopamine, alamin, etc. can be used.

Correction of acidosis and application of histamine drugs.

Pay attention to keep warm and prevent colds, keep a record of care and do not move.

Acupuncture can be performed on acupuncture points in Zhongguan, Neiguan, Yintang, Hegu, Yongquan, etc.

Acupoints such as Neiguan, Hegu, Yongquan, Guan Yuan, Zhongli, etc. can be used for moxibustion ^[2] .

Penicillin encephalopathy

Penicillin encephalopathy is a rare central nervous system toxic reaction of penicillin. Usually only a small amount of penicillin passes through the blood-brain barrier, but when the dosage is too large and the intravenous drip rate is too fast, a large number of drugs quickly enter the brain tissue, that is, drugs in blood and cerebrospinal fluid. The increased concentration of serotonin, which interferes with normal nervous function and causes severe central nervous system reactions, such as hyperreflexia, sensory disturbances, hallucinations, convulsions, lethargy, etc., is called "penicillin encephalopathy". ^[8]

The pathogenesis of penicillin encephalopathy is unknown. The reason is that the drug inhibits the synthesis and transport of the central nervous inhibitory transmitter -aminobutyric acid (GABA) to a certain extent, and inhibits the Na + -K + -ATPase of the central nervous cells. Caused by the reduction of the potential of the membrane. Some literatures believe that it may be related to the cations in the sodium salt of penicillin. It is believed that the toxic effects of sodium, lithium, ammonium, strontium, calcium, magnesium, and potassium increase in order. In addition, it is related to the purity of the preparation, individual differences, dose size, injection method, speed, The concentrations are all related. Some scholars have proved that the concentration of penicillin G in the cerebrospinal fluid exceeds 8u-10u / ml, and toxic reactions can occur. Some people think that the poor function of the blood-brain barrier is the main reason. After penicillin enters the body, 90% is excreted by the kidneys. Infants with poor kidney function prolong their half-life, increase blood concentrations, increase toxicity, and cause neurotoxic effects. Lead to increased excitability of the brain-convulsions, or "penicillin encephalopathy. At present, penicillin consumption in infants is <600,000 u / kg · d, and neonates are <400,000 u / kg · d. It is input in several times within 24 hours, and renal dysfunction And those with poor circulation should be used with caution.

Due to impaired renal function in the elderly, the half-life of penicillin and other broad-spectrum penicillins is prolonged. For example, the intravenous injection of penicillin G has a half-life of 0.55 hours in 25-year-olds and 1.0 hours in 70-year-olds; Because penicillin half-life is 10 hours in 25-year-olds and 18 hours in 70-year-olds; dichloropenicillin has a half-life of 0.88 hours in young people less than 30 years of age and 3.97 hours in people older than 65 years; Intravenous ampicillin has a half-life of 1 hour to 1.5 hours in young people and 2.67 hours in 89-year-olds. At the same time, due to the reduction of plasma albumin production in the elderly, only 3.7% of those over 75 years of age, the absorption of antibiotics in the blood is correspondingly reduced, and its free portion is increased in the blood and tissues. When the elderly use large doses of penicillin G and carbenicillin, neuro-psychiatric symptoms can occur, such as hyperreflexia, sensory disturbances, hallucinations, convulsions, lethargy, etc., and temporary mental disorders can also occur, easily forming "penicillin encephalopathy".

Due to the immature blood-brain barrier function and renal function of children, high-dose penicillin can significantly increase the concentration of cerebrospinal fluid, produce toxic effects on the center, and lead to the occurrence of penicillin encephalopathy. In addition, one million penicillin G sodium contains Na + 39mg, and one million penicillin G potassium contains K + 66mg. Pay attention to the retention of K + and Na + in the body when a large amount of intravenous injection. It is also easy to form "penicillin encephalopathy".

When penicillin, especially penicillin G, is used too much systemically or intravenously, the penicillin concentration in the cerebrospinal fluid exceeds 8 U / ml, which can directly stimulate the cerebral cortex and cause severe reactions such as convulsions, convulsions, epilepsy and even coma. Usually appear within 24-72h after medication. It often occurs in newborns, children, and the elderly because drugs easily pass through their blood-brain barrier. For patients with renal failure or renal failure, it is also prone to occur due to drug excretion disorders.

Peripheral neuritis can occur in the intramuscular injection area of penicillin. Intrathecal injection of more than 20,000 units or intravenous infusion of large doses of penicillin can cause muscle clonics, convulsions, and coma. This response is more common in infants, the elderly and patients with impaired renal function. Penicillin can cause psychotic episodes. Individual patients may develop high fever, anxiety, and fever after applying procaine penicillin.

serious condition. The main manifestations are sudden convulsions, dehydration, hypoxia, shortness of breath, and changes in blood biochemistry (such as hypoglycemia, hyponatremia, acidemia), hypertension, fast heart rate, hallucinations, convulsions, Coma and respiratory failure. The mechanism of this reaction is unknown. Some children may also have limb paralysis, children with open cardia can see cardia bulge, and a few children may have uncoordinated movement. The above symptoms usually appear 1 to 2 weeks after the original disease.

Coma is long and may have severe sequelae. Sequelae may include stupidity, blindness, deafness, and paralysis. A small number of patients may die from serious illness.

treatment

Stop penicillin If penicillin encephalopathy occurs, stop penicillin in time. 2. Immediately inhale oxygen. For comatose patients, sputum should be aspirated, breathing should be kept unobstructed, oxygen should be provided in a timely manner for a long period of time, and brain edema should be resolved. If necessary, tracheotomy and artificial respiration should be performed. 3, anticonvulsant, use sedative, antipsychotic drugs intramuscular injection of lumina sodium, diazepam and so on. 4. Adrenal cortex hormones. Such as hydrocortisone, prednisone, and dexamethasone, all have rapid anti-inflammatory and anti-edema effects, and should be used for a short period of time, generally not more than one week. 5. An intravenous bolus of 20% mannitol, an anti-cerebral edema drug. It should be applied repeatedly in cases of repeated intracranial hypertension to prevent cerebral hernia. At the same time, fast diuretics can be added to enhance the effect of dehydrating agents. 6. Strengthen dialysis and cooperate with hemoperfusion, blood purification, etc. 7. Proper treatment for hyperthermia, dehydration, and blood biochemical changes (such as hypoglycemia, hyponatremia, acidemia) and respiratory failure. 8. Speeding up drug clearance can reduce mental symptoms. 9. Energy support therapy. Toxicity can be metabolized in hours and tens of hours, but the poisoned nerves are still in a state of paralysis shock. Without early treatment, the nerves of paralysis shock are activated and nourished, and the affected nerves will be too long due to ischemia. Delayed ischemic pathological changes, medically known as delayed neurological damage, are difficult to recover. 10. The prognosis of the vast majority of patients with this disease is good, and symptoms disappear within 24 hours after proper treatment, without sequelae. If the coma lasts for several days to several weeks, it may cause severe sequelae such as children's insufficiency, blindness, deafness, inflexible limbs or paralysis. A few can die in a short time due to respiratory failure. ^[8]

Precautions

Among the side effects of pacillin, anaphylactic shock is fatal and often attracts people's attention. The neurotoxic effects of encephalopathy and peripheral nerve damage are easily ignored. The idea that penicillin was rarely poisoned as long as it is not allergic must be dispelled. Do not abuse penicillin (including other antibiotics) in large doses. When it is necessary, use intravenous infusion as little as possible, especially for the elderly and children. It should also be noted that when penicillin is used in combination with ampicillin, penicillin encephalopathy is more likely to occur. ^[8]

When antibacterials are used in the elderly, the elimination process is significantly slower.

Paecilomycin was originally a highly effective and low-toxic antibiotic. It has made great achievements in the history of human anti-infection, and its prestige remains undiminished. It may be because of this that there is a tendency that penicillin is used more and more widely and the dosage is increasing. A small number of medical staff infused a large amount of penicillin into a patient's vein, especially an intravenous infusion of more than 8 million units, and some even used it several times a day and continued to use it for several days. This not only causes the high penicillin concentration in the blood, but also increases the penicillin concentration in the cerebrospinal fluid. When the concentration in the cerebrospinal fluid is> 8 units / ml, it will stimulate the cerebral nerves and then hyperreflexia, disturbance of perception, hallucinations, and convulsions. Encephalopathy symptoms such as coma and coma can also cause transient mental disorders, especially those with renal insufficiency, the elderly and children are more likely to induce the disease.

Due to renal dysfunction and decrease of plasma albumin, blood concentration and cerebrospinal fluid drug concentration are increased, resulting in central nervous system toxic reactions. Therefore, when using antibiotics in the elderly, the dosage should be adjusted according to renal function. In order to prevent the occurrence of "penicillin encephalopathy", the dosage of such drugs should not be too large. If the condition requires a large dose, it should be divided into 3 times daily. Give 4 times. Incidentally, many antibiotics such as cephalosporins, vancomycin, tetracycline, nalidixic acid, etc. can increase toxic and side effects due to decreased renal function and increased serum concentrations. Some drugs can be used in reduced amounts, and some are better not to use other antibiotics. ^[8]

A wide variety of antibiotics that can cause damage to the central nervous system, such as penicillin, cephalosporins, tenon, aminoglycosides, macrolides, chloramphenicol, polymyxin E, sulfonamide, quinolone, anti-paeonia isotonic Some drugs, such as hydrazine and antiviral drugs (aciclovir, ganciclovir), can cause neurological damage to varying degrees and cause various brain symptoms. ^[8]

Penicillin indications

Penicillin is used for infections caused by sensitive bacteria or sensitive pathogens. Pharyngitis, tonsillitis, scarlet fever, endocarditis, erysipelas, cellulitis, and puerperal fever caused by hemolytic streptococcus. Pneumonia caused by pneumococcus, otitis media, meningitis, and bacteremia. Tetanus and gas gangrene caused by Clostridium.

1. Penicillin G has better curative effect on pharyngitis, scarlet fever, cellulitis, septic arthritis, pneumonia, puerperal fever and sepsis caused by -hemolytic streptococcus in group A. It is the preferred drug. For severe infections above, 1.2 million to 1.6 million U each time is administered intravenously 4 times a day. Pharyngitis should be administered for at least 10 days to ensure that pathogenic bacteria are eliminated from the pharynx to avoid rheumatic fever in the future. Acute suppurative meningitis (meningitis) and endocarditis caused by Streptococcus pyogenes should be administered intravenously in large doses of penicillin G (10 million to 20 million U per day).

2. Other streptococcal infections: Including respiratory infections caused by -hemolytic streptococcus, Streptococcus grass and Streptococcus faecalis, acute suppurative meningitis (meningitis), endocarditis, and sepsis . Streptococcus pneumoniae is highly sensitive to penicillin G, and treatment with penicillin G is preferred.

3. Meningitis caused by meningococcus or other sensitive bacteria: Penicillin G does not easily penetrate the normal blood-cerebrospinal fluid barrier and enters the cerebrospinal fluid in a small amount, but the permeability increases when the meninges are damaged by inflammation, so high-dose treatment is effective . The starting dose for adults is 10 million to 20 million U per day, divided into 4 intravenous drips.

4. Gonorrhea caused by Neisseria gonorrhoeae: Neisseria gonorrhoeae is sensitive to penicillin G, but in recent years, the number of resistant bacteria has increased significantly, and some are highly resistant. Therefore, whether to use penicillin G or not should be determined based on the results of the sensitivity test. to make sure.

5. Syphilis caused by Treponema pallidum: Penicillin G is still the main therapeutic drug. For the second and third stage syphilis or the first stage heavier cases, especially those with early central nervous system symptoms, should be treated with large doses of penicillin G, 5 million to 20 million U per day, intravenous drip, only for 3 to 4 weeks of treatment Stable effect.

6. Infection caused by gram-positive bacteria: infections caused by tetanus, diphtheria, and anthrax should be treated with penicillin G and antitoxin. Penicillin is mainly used in the following diseases in dermatology: (1) Syphilis. (2) Gonorrhea. (3) Others such as scarlet fever, cellulitis, erysipelas, erysipelas, pyoderma, etc.

Dosage of penicillin

Common dosage for adults: Intramuscular injection, 800,000 to 2 million U per day, divided into 3 to 4 times; Intravenous infusion, 2 million to 10 million U per day, divided into 2 to 4 times.

Commonly used in children: Intramuscular injection, 25,000 U / kg, administered once every 12 hours. Intravenous administration, 5 to 200,000 U / kg daily, divided into 2 to 4 times.

Newborn dose: once 50,000 U / kg, intramuscularly or intravenously, once every 12 hours in the first week of birth,> 7 days every 8 hours, severe infection once every 6 hours.

Dose for premature infants: 30,000 U / kg in the first week, once every 12 hours, once every 8 hours in 2 to 4 weeks, and once every 6 hours thereafter.

Penicillin preparations and specifications

1. Penicillin sodium for injection: 0.12g (200,000 U); 0.24g (400,000 U); 0.48g (800,000 U); 0.6g (1 million U); 0.96g (1.6 million U) ; 2.4g (4 million U).

2. Penicillin potassium for injection: 0.125g (200,000 U); 0.25g (400,000 U); 0.5g (800,000 U); 0.625g (1 million U). ^[8]

Penicillin bacterial resistance

S. aureus is most resistant to penicillin. There are three main mechanisms by which bacteria develop resistance to penicillins:

Bacteria produce -lactamase, which inactivates penicillins

The target of penicillin action in bacteriathe change of penicillin binding protein

Cell wall permeability to penicillins is reduced.

Among them, the first mechanism is the most common and the most important.

Penicillin antibiotics have good water solubility. Most of the blood elimination half-life does not exceed 2 hours. They are mainly excreted by the kidney. Most species can be removed by hemodialysis.

According to the regulations of the Chinese Ministry of Health, penicillin skin tests are required before using penicillin antibiotics, and those who respond positively are banned. ^[8]

Penicillin considerations

Do not mix with alkaline drugs when administered orally or by injection to avoid decomposition failure. ^[3]

This product should not be mixed with tetracycline hydrochloride, kanamycin, polymyxin E, sulfadiazine sodium, adenosine triphosphate, coenzyme A, etc. to prevent precipitation or degrading.

Chloramphenicol and penicillin should not be used in combination, because chloramphenicol is a bacteriostatic agent and penicillin is a fungicide in the breeding period. The combined use can affect the antibacterial activity of penicillin and reduce its effectiveness. However, this issue is still controversial, and the opinions are different, because the combination of the two has a good clinical effect on Gram-positive bacteria, negative bacteria mixed infection and intracranial infection. The solution is to use penicillin for 2 to 3 hours before using chloramphenicol. ^[3]

Because this product can inhibit the activity of certain liver enzymes, it can interfere with the biotransformation of tolbutamide, phenytoin and dicoumarin in the human body, and can enhance the effects of tolbutamide and phenytoin. Both anti-coagulant effects of legumin and warfarin were enhanced.

Use with caution in infants, liver and kidney dysfunction, with caution in pregnant women at the end of pregnancy, and avoid in breastfeeding women. ^[3]

In addition to skin tests before applying penicillin, pay attention to the following points :

Inject penicillin to regular medical units with rescue equipment. In case of an allergic reaction, timely and effective rescue treatment can be obtained. At any time during the injection, dizziness, palpitations, sweating, breathing difficulties, and other discomforts should be immediately reported to the doctor and nurse.

After injection of penicillin, observe at least 20 minutes in the hospital and leave without discomfort.

Do not use penicillin in extreme hunger, in order to prevent the body's tolerance to drugs during fasting and reduce adverse reactions such as halo acupuncture.

The time of two injections should not be too close, it is better to be 4 ~ 6 hours. When intravenous penicillin is dripped, do not start too fast. It is advisable not to exceed 40 drops per minute. Observe no adverse reactions for 10 to 20 minutes and then adjust the infusion rate.

If you have a history of penicillin injection on the day and you feel dizzy, palpitation, sweating, breathing difficulties, etc. at home, you should send it to the hospital for treatment in time.

Seven points for ampicillin:

Ampicillin (including ampicillin containing ampicillin, etc.) is one of the fastest decomposing and allergic reactions in penicillins. Especially in acidic environments and high blood concentrations, ampicillin degradation is more likely to occur. Allergic drug rash, anaphylactic shock caused by the accumulation of products and stacks, and even life-threatening. In the clinical use of ampicillin, not only do skin tests, but also the following points:

First, a negative skin test does not imply no allergy. Most of the ampicillin allergic reactions are late, and allergic drug rashes can occur after several days of continuous medication, causing anaphylactic shock. For allergic drug rashes, the use of zismin, diphenhydramine, and dexamethasone can be resolved after discontinuation. For those who suddenly have symptoms such as dyspnea, chills, fever, decreased blood pressure, and increased heart rate, stop taking the medicine immediately, give oxygen, and use drugs such as adrenaline, dexamethasone, and calcium gluconate to rescue them.

Secondly, it should be used for a short period of time, and it is forbidden to administer a large amount of medicine for a long time, so as to avoid the continuous increase of blood concentration, which will cause the formation and accumulation of allergenic substances and cause allergic reactions.

Thirdly, it should be intravenously infused after being fully dissolved in a sufficient amount of normal saline. Generally speaking, 4 g of ampicillin needs to be dissolved in about 300 ml of normal saline (0.9% sodium chloride injection). It must not be dissolved in sugar, especially intravenous drip in hypertonic sugar (glucose injection with a concentration greater than 5%). Because sugar is acidic, it can not only reduce the antibacterial and bactericidal ability of ampicillin, but also promote self-decomposition and increase the chance of sensitization.

Fourth, patients with gout, uremia, diabetic ketoacidosis and lactic acidosis should use as little or no ampicillin as possible. The reason is that ampicillin can promote self-decomposition in an acidic environment and increase the possibility of sensitization.

Fifth, the patients themselves are allergic and should be avoided.

Sixth, it is usually administered intravenously. It should be slow or fast. Intravenous infusion is performed at a rate of not more than 60 drops per minute to prevent the blood concentration from increasing too fast and increasing the possibility of decomposition and allergy.

Seventh, before using it, you should find the exact evidence of pathogenic infections that are sensitive to this medicine, and avoid blind abuse, so as to avoid dysbiosis and fungal infection, which will increase the difficulty of treatment.

Contraindications to penicillin

People who are allergic to penicillin or other penicillin drugs are prohibited ^[3] .

Before medication, patients should be asked if they have a history of allergies. For those who have not used penicillin for 24 hours, an intradermal sensitivity test should be performed. Those with positive test results should be disabled. Those who are allergic to penicillin or other penicillin drugs, allergic diseases and allergic states are prohibited.

Penicillin Drug Interactions

(1) Combined with probenecid, aspirin, indomethacin and sulfa drugs, can reduce the excretion of penicillin drugs, increase the concentration of penicillin blood, enhance the effect, but may also increase the toxicity.

Probenecid can inhibit renal tubular secretion, so it can prolong the maintenance time of penicillin blood concentration and have a synergistic effect on penicillin.

(2) Combined with bacteriostatic drugs such as tetracycline, erythromycin, chloramphenicol and sulfonamides, it may reduce the antibacterial effect of this product.

Penicillins are antagonistic to bacteriostatic drugs such as tetracycline, chloramphenicol, and macrolides. Because penicillin is a bactericidal drug in the breeding period, under the action of bacteriostatic drugs, bacterial reproduction is inhibited, which may cause the penicillins to play an insufficient role.

(3) Combined with warfarin, it can strengthen the anticoagulant effect.

(4) Taking contraceptives at the same time may affect the contraceptive effect.

(5) Penicillins and aminoglycoside antibiotics have a synergistic effect, but large doses of penicillin G or other semi-synthetic penicillins can reduce the activity of aminoglycosides.

Penicillin Drug Standard

National Penalin-Related National Retail Guide Price Information

Serial number	Essential medicines Directory number	Drug Name	Dosage form	specification	unit	Retail Price	category	Remark
1	1	penicillin	injection	800,000 units	Bottle (piece)	1 Yuan	Chemicals and biological products	*
2	1	penicillin	injection	1.6 million units	Bottle (piece)	1.8 yuan	Chemicals and biological products
3	1	penicillin	injection	4 million units	Bottle (piece)	3.5 yuan	Chemicals and biological products
4	1	penicillin	injection	8 million units	Bottle (piece)	5.5 yuan	Chemicals and biological products

Explanation :

Those marked with "*" in the remarks column of the table are representative products.

In the table, the representative dosage form specifications are marked with "" in the remarks column. The prices of the representative dosage form specifications and related specifications with a clear price comparison relationship are temporary prices.

Dose for patients with impaired renal function: When the glomerular filtration rate (GFR) is 10 to 15 ml / min, the interval between dosing is extended from 8 hours to 8 to 12 hours or the dose is reduced by 25%. When the GFR is less than 10 ml / min, the administration interval is 12 to 18 hours or the dose is reduced to 25% to 50% of the normal dose. Generally speaking, patients with renal impairment are mild to moderate, and conventional doses are used without reduction. Those with severe renal impairment should adjust the dosage or prolong the administration time ^[4] .