municipal educational institution
secondary school No. 29
Traktorozavodsky district of Volgograd
city competition
educational and research
works of high school students
"Me and the Earth"
them. IN AND. Vernadsky
(section of chemistry)
RESEARCH WORK
ON THE TOPIC:
"Study of the properties of aspirin and its effect on the human body".
Completed:
11th grade students
MOU secondary school №29
Gulina Victoria,
Nikiforov Dmitry
Supervisor:
chemistry teacher MOU secondary school №29
Travina Maria Evgenievna.
Volgograd - 2015
TABLE OF CONTENTS.
INTRODUCTION __________________________________________________3
CHAPTER 1. Literature review________________________________________________5
1.1. The history of the creation of aspirin _________________________ ________5
1.2. Pharmacological action of aspirin ______________________ 8
1.3. Chemical properties of acetylsalicylic acid ____________10
CHAPTER 2. Experimental part______________________________12
2.1. Study of the solubility of aspirin in water ____________________12
2.2. Determination of the pH of solutions containing acetylsalicylic acid _______________________________________________________________13
2.3. Determination of the solubility of aspirin in ethanol ______14
2.4. Determination of a phenol derivative in solution _________________15
2.5. Studying the effect of aspirin on the growth of molds ______16
CONCLUSION_____________________________________________17
LITERATURE______________________________________________18
Introduction.
Acetylsalicylic acid is one of the most famous and widely used medicines in the world. There are more than 50 names - trademarks of drugs, the main active ingredient of which is this substance. Over 40,000 tons of aspirin are consumed worldwide every year. This unusual drug can be called a champion among medicines. Acetylsalicylic acid is a long-liver in the world of drugs, officially celebrated its centenary in 1999, and is still the most popular medical drug in the world.
Almost every person at least once in his life used this medicine. Initially, this drug was intended to reduce body temperature, then several more effects were found: such as analgesic, blood thinning, anti-inflammatory.
Undoubtedly, acetylsalicylic acid plays an important role in human life. But at the same time, there is an impressive list of side effects on the human body that occur when taking acetylsalicylic acid. The problem of the use of drugs lies in the reasonableness and literacy of their use.
Object of study: medicines containing acetylsalicylic acid.
Subject of study: physicochemical and pharmacological properties of aspirin.
Objective:
to study the characteristic physical and chemical properties, the mechanism of action and methods for the safe use of drugs containing acetylsalicylic acid.
To achieve this goal, the following tasks:
read the literature containing information about acetylsalicylic acid;
conduct chemical experiments proving the properties of acetylsalicylic acid;
to find out the effect of acetylsalicylic acid on the human body;
experimentally test the suppression of mold growth on food products using acetylsalicylic acid.
Chapter 1. Literature Review.
1.1. The history of the creation of aspirin.
The history of Aspirin is one of the longest and most beautiful in pharmacology. Even 2500-3500 years ago, in ancient Egypt and Rome, the healing properties of willow bark, a natural source of salicylates, were known as an antipyretic and analgesic. Papyri dating back to the 2nd millennium BC, found by the German Egyptologist Georg Ebers among other 877 medical prescriptions, describe recommendations for the use of myrtle leaves (also containing salicylic acid) for rheumatic pain and sciatica. About a thousand years later, the father of medicine, Hippocrates, in his instructions recommended the use of willow bark in the form of a decoction for fever and labor pains. In the middle of the eighteenth century The Rev. Edmund Stone, Oxfordshire country vicar, presented to the President of the Royal Society of London a report on the cure of fever with willow bark. Often, for pain relief, a decoction of willow bark was used in combination with poppy tincture. In this form, it was used until the middle of the 19th century, when the development of chemistry made it possible to start serious studies of the composition of medicines from plant materials.
So, in 1828, Professor of Chemistry at the University of Munich, Johann Buchner, isolated an active substance from willow bark - a bitter-tasting glycoside, which he called salicin (from Latin Salix - willow). The substance had an antipyretic effect and, upon hydrolysis, gave glucose and salicylic alcohol.
In 1829, the French pharmacist Henri Leroy hydrolyzed salicylic alcohol. In 1838, the Italian chemist Rafael Piria divided salicin into two parts, revealing that its acidic component has medicinal properties. In fact, this was the first purification of the substance for the further development of the drug.
In 1859, chemistry professor Hermann Kolbe of the University of Marburg uncovered the chemical structure of salicylic acid, allowing the opening of the first factory to produce it in Dresden in 1874.
However, all the willow bark therapeutics that existed at that time had a very serious side effect - they caused severe abdominal pain and nausea.
In 1853, the French chemist Charles Frederic Gerard, in the course of experiments, found a way to acetylate salicylic acid, but did not complete the work. And in 1875, sodium salicylate was used to treat rheumatism and as an antipyretic.
The huge popularity of sodium salicylate awakened the German chemist Felix Hoffmann, who worked at the Bayer enterprise, in 1897 to continue the research of S.F. Gerard. In collaboration with his leader Heinrich Dreser, based on the work of a French chemist, he developed a new method for obtaining an acetylated form of salicylic acid - acetylsalicylic acid, which had all the same therapeutic properties, but was much better tolerated by patients. This discovery can be called the foundation for the creation of the drug.
To assess the safety of the resulting drug, the world's first preclinical experimental studies on animals were carried out. Thus, the study of the pharmacological properties of the drug was the beginning of clinical trials of drugs, which since the end of the twentieth century. have become the cornerstone of evidence-based medicine.
The studies were completed successfully - the good anti-inflammatory activity of the drug was proved and it was recommended for therapeutic use.
March 6, 1899, when a new drug was patented at the Kaiser Patent Office, was the birthday of Aspirin.
The trade name is based on the Latin name of the plant - a variety of meadowsweet willow (Spiraea), from which salicylates were obtained for the production of the drug.
On February 27, 1900, F. Hoffman received a patent for his invention of acetylsalicylic acid in the United States.
In more than 100 years of active medical use, aspirin has not only not lost its relevance, but has expanded its scope in such diverse areas as pain relief, cold symptoms, and the prevention of cardiovascular diseases.
Scientific interest in the drug is inexhaustible.
1.2. Pharmacological action of aspirin.
Acetylsalicylic acid has an anti-inflammatory, antipyretic and analgesic effect, it is widely used for fever, headache, neuralgia, and also as an antirheumatic agent.
The anti-inflammatory effect of acetylsalicylic acid is explained by its influence on the processes occurring in the inflammation focus: a decrease in capillary permeability, a decrease in hyaluronidase activity, a restriction of the energy supply of the inflammatory process by inhibiting the formation of ATP, etc. Inhibition of prostaglandin biosynthesis is important in the mechanism of anti-inflammatory action.
The blood-thinning effect of aspirin allows it to be used to reduce intracranial pressure, with the risk of blood clots. It has been proven that long-term use of a small dose of acetylsalicylic acid by people prone to diseases of the cardiovascular system significantly reduces the risk of stroke and myocardial infarction.
Like any drug, acetylsalicylic acid is not safe. Overdose can lead to poisoning, manifested by nausea, vomiting, stomach pain, dizziness, and in severe cases, toxic inflammation of the liver and kidneys, damage to the central nervous system and hemorrhages. If a person takes several medications at the same time, you need to be especially careful. Some drugs are incompatible with each other, and because of this, poisoning can occur. Acetylsalicylic acid increases the toxic effects of sulfonamides, enhances the effect of painkillers and anti-inflammatory drugs such as amidopyrine, butadione, analgin. This medicine also has side effects. It leads to irritation of the mucous membranes of the stomach. To avoid negative effects on the gastrointestinal tract, it is recommended to take this medicine after meals with plenty of fluids. However, it should be borne in mind that these measures do not reduce the risk of gastrointestinal bleeding. Therefore, it is better not to abuse acetylsalicylic acid, especially for people with gastritis or stomach ulcers. Pregnant women and young children should not take acetylsalicylic acid preparations unless absolutely necessary.
1.3. Chemical properties of acetylsalicylic acid.
Acetylsalicylic acid is a white small needle-like crystals or a light crystalline powder of a slightly acidic taste.
The full chemical name of acetylsalicylic acid is 2-acetoxy-benzoic acid
Physiochemical properties
Short chemical formula: C9H8O4
Molecular weight:180.2
Melting point: 133 - 138 0 C
Dissociation constant:
pKa = 3.7Acetylsalicylic acid is produced by heating salicylic acid with acetic anhydride:
Acetylsalicylic acid decomposes into and acetic acid. Hydrolysis is carried out by boiling a solution of acetylsalicylic acid in water for 30 seconds. After cooling, salicylic acid, which is poorly soluble in water, precipitates in the form of fluffy needle-shaped crystals.
When heated with sodium hydroxide in an aqueous solution, acetylsalicylic acid hydrolyzes to sodium salicylate and sodium acetate.
One part of acetylsalicylic acid dissolves in:
300 parts of water
20 parts of ether
17 parts of chloroform
7 parts 96% ethanol
Chapter 2. Experimental part.
2.1. Study of the solubility of aspirin in water.
To study the properties, we use drugs bought in a pharmacy containing acetylsalicylic acid: Upsarin Upsa, Aspirin - C, Acetylsalicylic acid.
Research methodology: crushed the tablets of each of the medicines in a mortar. Designated test tubes
№ 1 - ASPIRIN - C
№ 2 - UPSARIN UPSA
№ 3 - ACETYLALICYLIC ACID
0.1 g of each drug was transferred into test tubes. 10 ml of water was added to each test tube and the solubility of drugs in water was noted. Test tubes with substances were heated on an alcohol lamp.
Conclusions:
Test tube No. 1 - ASPIRIN - C - good solubility;
Tube No. 2 - UPSARIN UPSA - good solubility;
Tube No. 3 - ACETYLALYCYLIC ACID - poor solubility.
Acetylsalicylic acid, according to its physical properties, is slightly soluble in cold water. But Aspirin - C and Upsarin UPSA are well dissolved already in cold water. Acetylsalicylic acid in test tube No. 3 practically did not dissolve in cold water and also poorly dissolved after heating.
The result of the experiment shows that aspirin in test tube No. 3 is slightly soluble in water, therefore, once in the stomach, there is a risk that it will attach to the walls of the stomach and, irritating them, can cause ulcerative lesions.
2.2. Determination of the pH of solutions containing acetylsalicylic acid.
Research methodology: The pH of the test solutions in three test tubes was checked using universal indicator paper.
Conclusions:
Test tube No. 1 - ASPIRIN - C - pH=5
Tube No. 2 - UPSARIN UPSA - pH=7
Test tube No. 3 - ACETYLALICYLIC ACID - pH=3
Acetylsalicylic acid in test tube No. 3 showed increased acidity. The stomach contains a certain concentration of its hydrochloric acid, which is necessary for the disinfection and digestion of food, and an increase in the concentration of acid contributes to a violation of the acid balance of the stomach.
2.3. Determination of the solubility of aspirin in ethyl alcohol.
Research methodology: 0.1 g of drugs were added to test tubes and 10 ml of ethanol were added. Test tubes with substances were heated on an alcohol lamp.
Conclusions:
The results of the experiment showed that ASPIRIN in test tube No. 3 is better soluble in ethanol than in water, but precipitates in the form of crystals, ASPIRIN - C partially dissolved, and part of the drug formed a clearly distinguishable white precipitate, also a white precipitate, we observed in tube No. 2, where the UPSARIN UPSA was located.
The manufacturer's instructions for aspirin indicate that it is unacceptable to use it together with ethanol, this is also proven by our studies, which showed changes in the properties of drugs. It should be concluded that the use of aspirin in conjunction with alcohol-containing drugs, and even more so with alcohol, is inadmissible.
2.4. Determination of a phenol derivative (salicylic acid) in solution.
Research methodology: 0.1 g of each preparation was shaken with 10-15 ml of water and a few drops of iron chloride (III) were added. When added to the solution, a purple color appears.
Conclusions:
Tube No. 1 - ASPIRIN - C - brown-violet color
Tube No. 2 - UPSARIN UPSA - brown staining
Tube No. 3 - ACETYLALYCYLIC ACID - violet staining
As a result, it was found that during the hydrolysis of UPSARIN - UPSA, more acetic acid is formed than phenol derivatives, due to the fact that the violet color did not appear. And during the hydrolysis of ASPIRIN - C and ACETYLALYCYLIC ACID, on the contrary, more phenol derivatives are formed than acetic acid.
A phenol derivative is a substance that is very dangerous for human health, perhaps it is it that affects the appearance of side effects when taking acetylsalicylic acid.
2.5. Study of the effect of aspirin on the growth of mold fungi.
Research methodology: place slices of bread on 4 glasses, mark each glass with numbers (No. 1, 2, 3, 4, respectively), moisten glass No. 1 with water (control sample), glass No. 2 with ASPIRIN-C solution, glass No. 3 with UPSARIN-UPSA solution , glass No. 4 - with a solution of ACETYLSALICYLIC ACID. The samples were kept in a warm place in the presence of moisture, after three days we will notice a rapid growth of molds in the control sample. And where solutions of acetylsalicylic acid were added, mold was not observed.
Conclusions:
Acetylsalicylic acid, already in small concentrations, prevents the growth of mold fungi, as well as some bacteria. Therefore, they are used in large quantities for food preservation. The advantage of this substance is their low toxicity and the fact that it has almost no taste.
Conclusion.
In preparation for the studies, a review of the literature containing information about acetylsalicylic acid, its properties and application was performed.
During the experiments, the chemical properties of acetylsalicylic acid, as well as its effect on the human body, were proven.
The results of the experiments showed that aspirin is slightly soluble in water, ethyl alcohol, some varieties of the drug have high acidity and a high content of phenol derivatives.
The danger of aspirin lies in the fact that in the stomach it can lead to the appearance of erosive and ulcerative lesions and gastrointestinal bleeding.
It has been experimentally proven that acetylsalicylic acid inhibits the growth of molds on food.
You need to know that all drugs are effective only under certain conditions, which are always indicated in the attached instructions. Before using any drug, you should carefully read the instructions, as inept use or storage may pose a potential health hazard. Medicines must also be used as directed.
Literature.
Alikberova L.Yu. Entertaining chemistry: A book for students, teachers and parents. – M.: AST-PRESS, 2002.
Artemenko A.I. The use of organic compounds. – M.: Bustard, 2005.
Big encyclopedia. Cyril and Methodius 2005 CD - disc.
Dyson G., May P. Chemistry of synthetic medicinal substances. M.: Mir, 1964.
Mashkovsky M.D. Medicines. M.: Medicine, 2001.
Pichugina G.V. Chemistry and everyday life of a person. M.: Bustard, 2004.
Soviet Encyclopedic Dictionary, ch. ed. A.M. Prokhorov - Moscow, Soviet Encyclopedia, 1989
Vidal's Handbook: Medicines in Russia: A Handbook.- M.: Astra-PharmService.- 2001.
Shulpin G.B. This fascinating chemistry. M.; Chemistry, 1984.
ASPIRIN, the common name for acetylsalicylic acid - the most common pain reliever, antipyretic and anti-inflammatory agent. Acetylsalicylic acid and a number of other chemical derivatives of salicylic acid are collectively known as salicylates. Salicylates are one of the oldest medicines. Even in ancient times, various willow bark extracts were used to treat infectious diseases and gout, to relieve pain and reduce temperature. In 1838 it was shown that its active ingredient is salicylic acid. In 1860, this acid was first obtained artificially, and from 1875 its sodium salt began to be used.
The search for substances comparable in effectiveness, but less toxic than salicylic acid, was crowned with success when S. Gerhardt received acetylsalicylic acid in France. The salicylic acid molecule consists of six carbon atoms connected in a ring to which functional groups are attached, for example hydroxyl (combination of oxygen and hydrogen: OH). Gerhardt replaced the hydrogen atom (H) of the hydroxyl group with acetyl (COCH 3) and thus converted salicylic acid into acetyl salicylic. In 1893, F. Hoffmann, an employee of the Bayer company (Germany), developed a technology for the production of acetylsalicylic acid. The commercial name of the product "aspirin", according to its first manufacturers, is composed of two parts: "a" from acetyl and "spir" from Spiraea, the Latin name for meadowsweet - the plant from which salicylic acid was first chemically isolated.
Aspirin immediately and for a long time gained popularity. It and closely related substances are now found in more than 400 over-the-counter medications used to treat headaches and arthritis. In the United States, up to 20 tons of aspirin are consumed annually.
Recent clinical studies have shown that taking small doses of aspirin daily prevents insufficient blood supply to the heart (coronary artery occlusion) and brain (stroke). This deficiency is caused by fatty deposits that narrow the lumen of the arteries - as a result, blood flow in these vessels decreases and the risk of their blockage by blood clots increases. The main stage in the formation of blood clots is the adhesion of platelets. Aspirin is able to reduce the aggregation of platelets, irreversibly inhibiting their function.
Aspirin also blocks the production of prostaglandins, hormone-like substances that appear to be involved in inflammation, platelet aggregation, increased blood vessel permeability, and elevated body temperature. In the body, prostaglandins are formed from fatty acids under the action of special enzymes - cyclooxygenases. Aspirin serves as a powerful inhibitor of cyclooxygenases and thereby reduces the amount of prostaglandins and, accordingly, their undesirable effect.
Unfortunately, aspirin remains a common cause of poisoning in young children. In addition, according to some reports, the treatment of children with aspirin for influenza or chickenpox increases the risk of developing Reye's syndrome, a disease that is fatal in 20-40% of cases.
NSAIDs. Antiplatelet agent
Active substance
Release form, composition and packaging
10 pieces. - cellular contour packings (2) - packs of cardboard.
◊ Tablets white, round, slightly biconvex, beveled to the edge, with an imprint in the form of a brand name ("Bayer" cross) on one side and "ASPIRIN 0.5" on the other.
Excipients: microcrystalline cellulose, corn starch.
10 pieces. - blisters (1) - packs of cardboard.
10 pieces. - blisters (2) - packs of cardboard.
10 pieces. - blisters (10) - packs of cardboard.
pharmachologic effect
Acetylsalicylic acid (ASA) belongs to the group of non-steroidal anti-inflammatory drugs (NSAIDs) and has analgesic, antipyretic and anti-inflammatory effects due to the inhibition of cyclooxygenase enzymes involved in the synthesis of protaglandins.
ASA in the dose range of 0.3 to 1.0 g is used to reduce fever in diseases such as colds and flu, and to relieve joint and muscle pain. ASA inhibits platelet aggregation by blocking the synthesis of thromboxane A2 in platelets.
Indications
- for the symptomatic relief of headache, toothache, menstrual pain, muscle and joint pain, back pain;
- elevated body temperature with colds and other infectious and inflammatory diseases (in adults and children over 15 years old).
Contraindications
- erosive and ulcerative lesions of the gastrointestinal tract (in the acute phase);
- hemorrhagic diathesis;
- bronchial asthma induced by taking salicylates and other NSAIDs;
- combined use with a dose of 15 mg per week or more;
- I and III trimesters of pregnancy and the period of breastfeeding;
- hypersensitivity to ASA, other NSAIDs or any excipients of the drug.
The drug is not prescribed to children under 15 years of age with acute respiratory diseases caused by viral infections, due to the risk of developing Reye's syndrome (encephalopathy and acute fatty liver with acute liver failure).
FROM caution - with concomitant treatment, gout, hyperuricemia, peptic ulcer of the stomach and / or duodenum (in history), including chronic or recurrent peptic ulcer, as well as gastrointestinal bleeding; bronchial asthma, nasal polyposis, chronic broncho-pulmonary diseases; in case of impaired renal and / or liver function; in the second trimester of pregnancy.
Dosage
The drug is intended for adults and children over 15 years old:
At pain syndrome of low and moderate intensity and febrile conditions a single dose is 0.5-1 g, the maximum single dose is 1 g. The intervals between doses of the drug should be at least 4 hours. The maximum daily dose should not exceed 3 g (6 tablets).
Take orally, after meals, with plenty of liquid.
The duration of treatment (without consulting a doctor) should not exceed 7 days when prescribed as an anesthetic and more than 3 days as an antipyretic.
Side effects
From the gastrointestinal tract: abdominal pain, nausea, vomiting, heartburn, obvious (vomiting blood, tarry stools) or hidden signs of gastrointestinal bleeding, which can lead to iron deficiency anemia, erosive and ulcerative lesions (including those with perforation) of the gastrointestinal tract , increased activity of liver enzymes.
From the side of the central nervous system: dizziness and tinnitus (usually signs of an overdose).
From the hematopoietic system: increased risk of bleeding.
Allergic reactions: urticaria, anaphylactic reactions, bronchospasm, angioedema.
Overdose
Symptoms
For an overdose of moderate severity are characteristic nausea, vomiting, tinnitus, hearing loss, headache, dizziness and confusion. These symptoms disappear with a decrease in the dose of the drug.
Severe overdose is characterized by fever, hyperventilation, ketosis, respiratory alkalosis, metabolic acidosis, coma, cardiogenic shock, respiratory failure, severe hypoglycemia.
Treatment: hospitalization, lavage, activated charcoal, acid-base balance control, alkaline diuresis to obtain urine pH values in the range of 7.5-8.0 (forced alkaline diuresis is achieved when the concentration of salicylate in the blood is more than 500 mg / l (3.6 mmol / l) in adults and 300 mg / l (2.2 mmol / l) in children, hemodialysis, fluid replacement, symptomatic therapy.
drug interaction
Acetylsalicylic acid enhances the toxicity of methotrexate, the effects of narcotics, other NSAIDs, hypoglycemic agents for oral administration, heparin, indirect anticoagulants, thrombolytics - inhibitors of platelet aggregation, sulfonamides (including co-trimoxazole), triiodothyroquine; reduces - uricosuric drugs (benzbromarone, probenecid). antihypertensive drugs and diuretics (, furosemide).
Glucocorticosteroids, alcohol and ethanol-containing drugs increase the damaging effect on the gastrointestinal mucosa, increase the risk of gastrointestinal bleeding.
Acetylsalicylic acid increases the concentration of digoxin, barbiturates and lithium preparations in the blood.
special instructions
Children under 15 years of age should not be prescribed a drug containing acetylsalicylic acid, since in the case of a viral infection, the risk of Reye's syndrome increases.
Acetylsalicylic acid can cause bronchospasm, an asthma attack, or other hypersensitivity reactions. Risk factors are a history of bronchial asthma, fever, nasal polyps, chronic broncho-pulmonary diseases, a history of allergies (allergic rhinitis, skin rashes).
Acetylsalicylic acid may increase bleeding tendency due to its inhibitory effect on platelet aggregation. This should be considered if surgery is needed, including minor interventions such as tooth extraction. Before surgery, to reduce bleeding during surgery and in the postoperative period, you should stop taking the drug for 5-7 days and notify the doctor.
Acetylsalicylic acid reduces the excretion of uric acid from the body, which can cause an acute attack of gout in predisposed patients.
Pregnancy and lactation
If necessary, the use of the drug during lactation, breastfeeding should be discontinued.
Contraindicated for use in the I and III trimesters of pregnancy, in the II trimester caution is required.
Terms and conditions of storage
Store at a temperature not exceeding 30 ° C, out of the reach of children. Shelf life - 5 years.
Do heroin and aspirin have the same creator?
Friedrich Bayer
Friedrich Bayer was born in 1825. He was the only son in a family of six children. His father was a weaver and dyer, and Bayer followed in his footsteps. In 1848, he opened his own paint business, which quickly became successful. In the past, all dyes were made from organic materials, but in 1856 dyes were discovered that could be made from coal tar derivatives, sparking a revolution in the textile industry. 
Bayer and Friedrich Wescott (chief painter) saw the great potential for the development of this direction, and in 1863 they created their own company for the production of paints "Friedrich Bayer et Compagnie".
Aspirin Hoffman.
Bayer died on May 6, 1880, at which time his company was still in the fabric dye business. The company continued to hire chemists to come up with innovative 
e paints and products, and in 1897 luck smiled at one of the chemists. His name was Felix Hoffman.
The persistent chemist was looking for a cure for his father's rheumatism. And as a result of experiments with an unnecessary product of one of the components of the paint, he was able to chemically synthesize a stable form of salicylic acid powder.
The compound has become the active ingredient in many pharmaceutical products called "aspirin". The name comes from "a" from acetyl, and "spir" from the name of the spirea plant, (Filipendula ulmaria, also known as Spiraea ulmaria or meadowsweet), a source of salicin.
Another version of the origin of the name was the name of the patron saint of all those suffering from a headache, St. Aspirinus.
This medicine has been used for 3500 years!
However, Hoffman was not the first to discover and synthesize "aspirin". 40 years earlier, the French chemist Charles Gerhardt had already synthesized acetylsalicylic acid. In 1837, Gerhardt came up with good results, but the procedure was complicated and time consuming. So he decided it was not practical and put the experiments on hold. However, Gerhardt was quite well aware of the potential possibilities of treatment with acetylsalicylic acid, because this has been known for over 3500 years!
In early 1800, German Egyptologist Georg Ebers bought papyri from an Egyptian street vendor.
The Ebers Papyrus is known to have contained a collection of 877 medicinal prescriptions dating back to 2500 BC and specifically recommended that an infusion of dried myrtle be used to relieve rheumatic back pain.
As early as 400 BC, Hippocrates, the father of all doctors, recommended extracting tea from the bark of the willow tree to treat fever and pain.
The active ingredient in this juice that actually actually relieves pain, as we know today, is salicylic acid.
Scientists have confirmed that the bitter part of the willow bark is a natural source of the chemical salicin. This chemical can be converted to salicylic acid. Aspirin is a member of this family of chemicals named after salicylic acid esters.
In China and Asia, among the North American Indians and the tribes of South Africa, the beneficial effects of plants containing salicylic acid have been known since early times.
Breakthrough and authorship.
One of the first to try to meet the need for a synthetic substitute for natural antipyretics was the German company Heyden Chemical Co, which built its own salicylic acid factory in 1874.
However, while the salicylic acid extracted from willow bark did reduce pain, its side effect was severe stomach and mouth irritation. Patients of that time were faced with a choice: the harmless expensive salicin (in London in 1877 it cost about 50 pence an ounce) or cheap salicylic acid (5 pence an ounce) with a risk to the stomach.
Hoffmann's breakthrough came on August 10, 1897, when he first produced a 100% chemically pure form of acetylsalicylic acid, i.e. without natural salicylic acid.
On March 6, 1899, Bayer registered aspirin as a trademark. But still not without problems.
Deputy Dean of the Faculty of Pharmacy at the University of Strathclyde in Glasgow, Professor Walter Snyder put forward his version of authorship. According to her, the creator of aspirin is Arthur Eichengrün, also a Bayer chemist, but of Jewish origin, unlike Hoffman with Aryan roots. By the time of publication in the history of the sick father and the authorship of Hoffman in 1934 in Germany, this was quite relevant for well-known reasons.
Humanity still uses other inventions of Eichengrün to this day: these are fireproof films, fabrics, plastic furniture and antifreeze.
Despite the successful cooperation of the scientist with this largest German concern in 1944, the 76-year-old chemist was nevertheless sent to the Theresienstadt concentration camp in the Czech Republic, and his property was confiscated. 
In 1945 he was liberated by the Red Army. And only shortly before his death (“horrified by the very thought that injustice would triumph for another half century”), in his article-testament in Pharmazie, he wrote the true development of events. Eichengrün outlived his article by two weeks. Bayer AG does not support this version of the birth of aspirin.
Initially, the achievement of the company in 1899 received trade certificates only in the United States. In England and Germany, other companies insisted on their own authorship.
However, Hoffman's written evidence prevailed at the time, and the company patented a process for mass production of aspirin. And she thought of publishing a 200-page catalog of her medicines, among which the novelty stood out especially, and sending it to 30,000 practicing doctors in Europe. .
And when Hoffman retired in 1928, aspirin was known all over the world. Despite this, the chemist lived until his death on February 8, 1946 in Switzerland as an unrecognized author.
Do aspirin and heroin share the same creator?
Aspirin was Bayer's most remarkable success, but not the only one. A few days after Hoffman had succeeded in synthesizing acetylsalicylic acid, he produced another compound for which the Bayer company had big plans. Today, this discovery is of dubious value.
Diacetylmorphine (or heroin), a substance that had also been discovered several decades earlier by the English chemist C.R.A. Wright. Heroin was cautiously recommended by pharmacists during World War I, but by 1931 it had disappeared from the drug lists in almost every country. In 1924, a federal law was passed in the United States that banned its production, sale and consumption.
Additional facts.
Felix Hoffmann was born in Ludwigsburg in 1868. He carried out his pharmaceutical research at the University of Munich. April 1, 1894 joined Friedrich Bayer & Co. After the discovery of pure acetylsalicylic acid, he became the head of the pharmaceutical department.
Friedrich Bayer's company initially produced only anilines. Its founder died in 1880, unaware that Bayer was destined to become a pharmaceutical giant. By 1891, Bayer introduced a different product range. Today, it is more than 10,000 products.
In the 1930s, an employee of the company, (surprisingly) bearing the same last name (Otto Bayer), invented polyurethane.
German microbiologist Gerhard Domagk ("Bayer"), together with colleagues discovered the therapeutic effect of sulfonamides. This discovery revolutionized the chemotherapy of infectious diseases, and Domagku won the Nobel Prize in 1939.
Since 1950 aspirin has become known as a preventative drug in the fight against heart disease, in 37.6% of cases people take aspirin in this capacity (only 23.3% for headaches).
Aspirin was also used in space as part of the first aid package for the American astronauts of Apollo 11 (lunar module).
The Bayer company is constantly fighting the "leftist" manufacturers of its famous aspirin. That is why the well-known "Soviet" aspirin has long been called acetylsalicylic acid.
Acetylsalicylic acid is one of the most famous and widely used medicines in the world. There are more than 50 names - trademarks of drugs, the main active ingredient of which is this substance. Over 40,000 tons of aspirin are consumed worldwide every year. This unusual drug can be called a champion among medicines. Acetylsalicylic acid is a long-liver in the world of drugs, officially celebrated its centenary in 1999, and is still the most popular medical drug in the world. Despite its considerable age, aspirin is fraught with many mysteries.
Almost every person used this drug at least once in their life, everyone pursued different goals: someone lowered the temperature, someone reduced pain and inflammation, and someone “thinned the blood”.
Each of us has this tool in the home first-aid kit, but only a few know about its multidirectional action. Some do not even realize that he saves someone's life every day!
People who have had a heart attack or stroke should take it for life to reduce the risk of developing a second episode of a vascular accident. According to the Society of Cardiology of the Nizhny Novgorod region for 2009, about 24-30% of Nizhny Novgorod residents use aspirin every day.
Patients suffering from joint disease take it not only to reduce pain, but also to reduce inflammation in the joints, increase their mobility, reduce the rate of development of secondary complications and, first of all, to improve the quality of life.
You can give examples of the use of aspirin for a long time and try to reflect the points of its application. This suggests that in pharmacology there is no more interesting, significant from a practical and scientific-experimental point of view and at the same time a controversial drug than acetylsalicylic acid. This is confirmed by its long-term use for the treatment of many different pathological conditions.
Hypothesis: aspirin has a wide range of applications, has both positive and side effects.
The purpose of the work: to prove the universality of application in everyday life.
Tasks: to study the properties of aspirin, consider the points of application of the drug and the effect of ACS on the human body, trace its path from discovery to synthesis.
Research methods: analysis of scientific literature and Internet resources, practical work, formulation of conclusions.
1. Structure and physico-chemical properties.
Acetylsalicylic acid, which has analgesic, anti-inflammatory and antiplatelet properties, belongs to the group of non-steroidal anti-inflammatory drugs, which, in addition to aspirin itself and other salicylates, includes well-known drugs of various chemical structures (for example: orthophene, indomethacin, butadione, etc.).
Acetylsalicylic acid, or aspirin, is an ester formed by acetic and salicylic acid, the latter reacting as a phenol in the formation of this ester.
2-acetyloxybenzoic acid Molecular formula C9H8O4
In appearance, acetylsalicylic acid is a white crystalline powder or colorless crystals, odorless or with a faint odor, slightly acidic taste. Unlike salicylic acid, pure acetylsalicylic acid does not react with FeCl3, since it does not have free phenolic hydroxyl. Acetylsalicylic acid, as an ester formed by acetic acid and phenolic acid (instead of alcohol), is very easily hydrolyzed. Already when standing in moist air, it hydrolyzes into acetic and salicylic acids. In this regard, pharmacists often have to check whether acetylsalicylic acid has been hydrolyzed. For this, the reaction with FeCl3 is very convenient: acetylsalicylic acid does not give color with FeCl3, while salicylic acid, formed as a result of hydrolysis, gives a violet color.
Acetylsalicylic acid is slightly soluble in water, easily soluble in 96% alcohol, ether soluble. It is highly soluble in alkali solutions, little in water (1:300), ethanol (1:7), chloroform (1:17), diethyl ether (1:20). Melts at a temperature of about 143 0C, Obtained by acetylation of salicylic acid with acetic anhydride.
The analysis for the content of acetylsalicylic acid is carried out as follows: 1.00 g of the substance is placed in a flask with a ground glass stopper, dissolved in 10 ml of 96% alcohol. 50.0 ml of 0.5 M sodium hydroxide solution is added, the flask is closed and kept for 1 hour. The resulting solution is titrated with 0.5 M hydrochloric acid solution, using 0.2 ml of phenolphthalein solution as an indicator.
In parallel, a control experiment is carried out: 1 ml of 0.5 M sodium hydroxide solution corresponds to 45.04 mg C9H8O4.
In acetylsalicylic acid, if it is not properly stored, impurities are formed:
4-hydroxybenzoic acid;
4-hydroxybenzene-1. 3-dicarboxylic acid (4-hydroxyisophthalic acid).
2-[hydroxy]benzoic acid.
2. History of discovery.
The history of the creation, study and use of acetylsalicylic acid resembles an adventure novel full of unexpected plot twists and incredible collisions.
Willow bark Salix alba is a well-known folk medicine antipyretic. It contains a bitter-tasting substance - salicylic acid glycoside. It was salicylic acid that became the precursor to aspirin.
Even 2500-3500 years ago, in ancient Egypt and Rome, the healing properties of willow bark (a natural source of salicylates) were known as an antipyretic and analgesic. On papyri dating back to the 2nd millennium BC. e. found by the German Egyptologist Georg Ebers among 877 other medical prescriptions, describes recommendations for the use of myrtle leaves (also containing salicylic acid) for rheumatic pain and sciatica. About a thousand years later, the father of medicine, Hippocrates, in his instructions recommended the use of willow bark in the form of a decoction for fever and labor pains. In the middle of the 18th century, the Reverend Edmund Stone, a country vicar from Oxfordshire, presented to the President of the Royal Society of London a report on the cure of fever with willow bark.
And at the beginning of the 18th century, the bark of the “febrile trembling” tree was delivered from Peru to Europe, with which the Indians treated “swamp fever” and which they called kina - kina. The powder of this bark was renamed "quina" and was used for "fever" and "fever" of all kinds. But quinine, and subsequently its active principle - quinine, were expensive, so they were looking for a substitute for it.
In 1828, professor of chemistry at the University of Munich Johann Buchner isolated an active substance from willow bark - a bitter-tasting glycoside, which he called salicin (from Latin Salix - willow). The substance had an antipyretic effect and, upon hydrolysis, gave glucose and salicylic alcohol.
In 1829, the French pharmacist Henri Leroy hydrolyzed salicylic alcohol.
In 1838, the Italian chemist Rafael Piria divided salicin into two parts, revealing that its acidic component has healing properties. In fact, this was the first purification of the substance for the further development of acetylsalicylic acid.
The acetyl group (top left) is connected via an oxygen atom (indicated in red)
with salicylic acid.
In 1859, chemistry professor Hermann Kolbe of the University of Marburg revealed the chemical structure of salicylic acid, which allowed the opening of the first factory for its production in Dresden in 1874.
However, all willow bark therapeutics that existed at that time had a very serious side effect - they caused severe abdominal pain and nausea and were discontinued.
In 1853, the French chemist Charles Frederic Gerard, in the course of experiments, found a way to acetylate salicylic acid, but did not complete the work. And in 1875, sodium salicylate began to be used to treat rheumatism and as an antipyretic.
Further history is already beginning to have a detective character, according to the surviving documentation, the huge popularity of sodium salicylate prompted the German chemist Felix Hoffmann, who worked at the Bayer enterprise, in 1897 to continue the research of Ch. F. Gerard. In collaboration with his leader Heinrich Dreser, based on the work of a French chemist, he developed a new method for obtaining an acetylated form of salicylic acid - acetylsalicylic acid, which had all the same therapeutic properties, but was much better tolerated by patients. This discovery can be called the foundation for the creation of ASPIRIN®.
The story goes that F. Hoffmann's father, a Württemberg manufacturer, suffered from rheumatic pain and could not move. To reduce the severity of the pain syndrome, doctors prescribed him sodium salicylate, but after each dose of this drug, Hoffman Sr. began to vomit. In this regard, Hoffman Jr., on his own initiative, began to work to improve the natural substance - salicylic acid. As follows from the laboratory diary, on August 10, 1897, F. Hoffman became the first chemist on the globe who managed to obtain salicylic acid in a chemically pure and stable form by acetylation.
As was established by F. Hoffman, acetylsalicylic acid could be stored for a long time without losing its therapeutic activity. Industrial production of acetylsalicylic acid began in 1893.
Initially, aspirin was produced in the form of a powder packaged in glass vials. Tablet production began in 1914.
March 6, 1899 - the day when acetylsalicylic acid was registered as a commercial drug under the name Aspirin - was the day that marked a real breakthrough and can also be considered the birthday of real commercial pharmacology. This drug was the first truly synthetic drug with developed optimal industrial synthesis. A successful, memorable commercial name and its entry into the non-prescription group in 1915 led to its widespread distribution and the subsequent scientific search with the creation of a whole group of NSAID drugs. Immediately after the release, the drug gained very great popularity and for more than 100 years has not left the shelves of all pharmacies in the world. Only in the USA, where for some reason aspirin enjoys special love of the population, it is produced in the amount of 12 thousand tons, or 50 billion single doses, per year! In our country, aspirin began to be produced under the chemical name - acetylsalicylic acid (ASA), but in fact it is produced by different companies under more than sixty names, which also indicates its popularity. Initially, ASA was classified as an antipyretic, although it is impossible to explain all its positive properties, in particular in rheumatism, by a decrease in temperature. When phenacetin and paracetamol appeared, which reduced elevated body temperature, but did not have an anti-inflammatory effect, like ASA, they began to be considered antipyretic (antipyretic) drugs.
Currently, ASA is sold under more than 400 trade names, exists in at least 15 dosage forms and, according to rough estimates, is included in about one and a half thousand combined drugs worldwide. ASA is also the most researched and studied drug currently in use.
3. Obtaining ACS.
3. 1. Industrial production.
In industry, aspirin is obtained in the course of a multi-stage synthesis from toluene, which in turn is a large-scale industrial product.
Toluene (I) is chlorinated in the presence of a catalyst (AlCl3):
The adduct (II) is oxidized with atomic oxygen (ozone) at a temperature of t=0-5 0С in an aqueous emulsion:
The resulting o-chlorobenzoic acid(III) is saponified with a 30% aqueous solution of sodium hydroxide:
The salt form of salicylic acid (IV) is converted into a free acid:
Salicylic acid (V) is acylated with acetic anhydride, and aspirin (VI) is obtained:
Al2O3, +(CH3COO)2H
OH O–C–CH3
(VI) recrystallized from water and sent for packing.
3. 2. Laboratory receipt.
In the laboratory, acetylsalicylic acid (Aspirin) can be obtained (a) according to a slightly modified scheme: A)
CH2=CH–CH3
H2SO4 NaOHwater CO2
4. Pharmacology.
For many decades, aspirin was thought to have three main effects: anti-inflammatory, antipyretic, and less pronounced analgesic.
How are these effects of aspirin realized, or, as pharmacologists say, what are the mechanisms of action? They are complex, interrelated and still not well understood.
4. 1. Anti-inflammatory action
It is due to the suppression of the second, exudative phase of inflammation, characterized by the release of the liquid part of the blood through the vascular wall, which leads to tissue edema. Aspirin reduces the formation and effect on the vessels of inflammatory mediators, such as histamine, bradykinin, hyaluronidase, prostaglandins. As a result, vascular permeability decreases and exudation is weakened. Salicylates disrupt the synthesis of ATP, worsening the energy supply of the inflammatory process (sensitive to lack of energy), in particular the migration of leukocytes. The stabilizing effect on cell lysosome membranes prevents the release of aggressive lysosomal enzymes and thereby weakens the destructive phenomena in the focus of inflammation.
And yet, the main role in the implementation of the anti-inflammatory effect of aspirin, like all NSAIDs, is assigned to the ability to inhibit the biosynthesis of one of the main mediators of inflammation - prostaglandins (PG). These endogenous biologically active substances are products of the transformation of arachidonic acid and are formed in various cells of the body under the influence of the enzyme cyclooxygenase (COX), which is blocked by aspirin. Arachidonic acid is released from membrane phospholipids by phospholipase A2.
However, the mechanism of COX inhibition by aspirin and other NSAIDs is not the same. Aspirin, covalently binding to the serine amino acid residue in the enzyme molecule, inhibits it irreversibly. As a result, there are steric obstacles to the attachment of the substrate (arachidonic acid) to the active center of COX. Unlike aspirin, Voltaren, ibuprofen and other NSAIDs bind COX reversibly. In the inflamed tissue, predominantly PGE 2 and PGI 2 are formed. They act on the vascular wall themselves and enhance the effect of other inflammatory mediators: histamine, bradykinin, serotonin.
Recently, a significant contribution to the therapeutic effect of aspirin on inflammation is made by the arachidonic acid metabolite lipoxin (LH) A4 (trihydroeicosotetraenoic acid). It is generated by different types of cells, including active participants in the inflammatory process, neutrophils and macrophages. The starting point in the induction of the synthesis (LC) of A4 is the acetylation of COX by aspirin. It has been established that lipoxins regulate cellular reactions of inflammation and immunity. It has been proven, in particular, that lipoxins sharply inhibit the release of IL-8, which causes accelerated maturation, chemotaxis, transendothelial migration, activation of neutrophilic leukocytes, and also activates macrophages and T-lymphocytes.
4. 2. Antipyretic effect
Antipyretic effect, apparently, is also associated with inhibition of PG synthesis. NSAIDs, and aspirin among them, do not affect normal or increased overheating (heat stroke) body temperature. Other conditions arise in infectious diseases. Endogenous pyrogens, mainly IL-1, are mobilized from leukocytes and increase the level of PGE 2 in the center of thermoregulation located in the hypothalamic region of the brain. As a result, the normal ratio of Na + and Ca 2+ ions is disturbed, which changes the activity of neurons of thermoregulatory brain structures. The result is an increase in heat production and a decrease in heat transfer. By suppressing the formation of PGE 2 and thereby restoring normal neuronal activity, aspirin reduces body temperature. The decrease in temperature occurs due to an increase in heat transfer as a result of the expansion of skin vessels, which occurs on command from the thermoregulation center. At present, based on the ideas about the protective role of temperature increase, it is rarely reduced on purpose. This is usually achieved as a result of exposure to the causative factor (the most common situation is the destruction of the causative agent of the infectious process with antibiotics).
However, antipyretic drugs are prescribed for children at a temperature of 38.5-39 ° C, which violates the general condition of the body, and for children with cardiovascular pathology and prone to convulsions - at a temperature of 37.5-38 ° C. At the same time, it is taken into account that in children with viral infections (flu, acute respiratory infections, chicken pox), taking aspirin carries a threat of developing Reye's syndrome, which is characterized by damage to the brain and liver and often leads to death. Therefore, pediatricians use ibuprofen, naproxen, and especially often paracetamol.
4. 3. Pain relief
The mechanism of analgesic (analgesic) action consists of two components: peripheral and central.
It is known that PG (PGE 2 , PGF 2a , PGI 2), having a moderate intrinsic ability to cause a sensation of pain, significantly increase the sensitivity (sensitize) the endings of nerve fibers to various influences, including inflammatory mediators - bradykinin, histamine, etc. Therefore, violation of PG biosynthesis leads to an increase in the threshold of pain sensitivity, especially in inflammation. The central component, possibly also associated with the inhibition of PG synthesis, consists in the inhibition of the conduction of pain impulses along the ascending nerve pathways, mainly at the level of the spinal cord. Compared to other NSAIDs, the analgesic effect of salicylates is rather weak.
The foregoing makes it clear that the combination of anti-inflammatory, analgesic and antipyretic properties in one drug cannot be considered accidental, since the action of PGs themselves is multifaceted, the influence on the formation of which is the main effect of aspirin (and other NSAIDs).
4. 4. Aspirin as an antiplatelet agent in cardiovascular diseases.
The use of aspirin in certain cardiovascular diseases, and primarily in coronary heart disease (CHD), is based on its ability to have an antithrombotic effect, which is expressed in the prevention of the formation of blood clots - thrombosis. A thrombus, a blood clot of different density, formed in the vessels, can impede or completely block the blood flow in the vessel, which leads to a violation of the blood supply (ischemia) of the corresponding organ or part thereof. Depending on the degree of ischemia, the ability to compensate for the lack of blood supply due to neighboring vessels, the importance of the organ, the consequences for the body can be different - up to a fatal heart attack of the heart or brain. A thrombus or its fragment can break off, move through the bloodstream and block another vessel (embolism) with similar consequences.
Therefore, an increased tendency to thrombosis plays an extremely important role in the course of many cardiovascular diseases. Equally obvious is the urgent need for antithrombotic agents. There are three groups of such drugs: fibrinolytic, anticoagulants and antiplatelet agents (antiplatelet).
1. Fibrinolytics are designed only to dissolve an already formed thrombus.
2. Anticoagulants - drugs that reduce blood clotting, used mainly for severe heart disease, because they require careful, weekly monitoring of blood clotting (dangerous bleeding can occur if the dose is incorrectly selected).
3. Antiaggregants (antiplatelet drugs) is the most widely used group of drugs, among which the undisputed leader is our friend aspirin (acetylsalicylic acid).
In order to understand all the points of application of acetylsalicylic acid in relation to reducing the risk of developing thrombosis, it is necessary to consider all the links of pathogenesis.
4. 5. Platelets, endothelium and thrombus formation.
Thrombus formation is the result of a complex interaction between the components of the vascular wall, platelets and plasma proteins of the blood coagulation and anticoagulation systems. Platelets are unable to settle on intact endothelium, which is a layer of flattened cells lining the walls of blood and lymphatic vessels from the inside. But if the integrity of the endothelial layer is violated, they easily adhere to subendothelial structures, especially to collagen (adhesion), which is ensured by the presence of glycoprotein receptors on platelet membranes. In this case, platelets release several substances, including adenosine diphosphate (ADP) and thromboxane, which are powerful aggregants. As a result, a close accumulation of platelets is formed with the formation of fibrinogen bridges between them (aggregation). There is a further release of ADP and thromboxane, activating inactive cells, the mass of platelets increases (snowball phenomenon), a platelet thrombus occurs. Enzymes, vasoactive peptides, blood coagulation factors are released from platelet granules, blood clotting increases, proteins of the coagulation system impregnate the platelet thrombus, one of them - fibrinogen is transformed into fibrin, which gives the thrombus density, the formation of a thrombus is completed.
The two most important participants in these events are thromboxane and prostacyclin (PGI 2), which are formed from arachidonic acid under the influence of COX, thromboxane - in platelets, prostacyclin - in endothelial cells. But their effects are antagonistic: prostacyclin dilates blood vessels and inhibits platelet aggregation, thromboxane acts in the opposite way. These effects are realized through a well-known mediator (messenger) of signal transmission into the cell - cAMP. Prostacyclin increases the content of cAMP, which retains Ca 2+ in a bound state, which leads to inhibition of platelet adhesion and aggregation, as well as to a decrease in the release of thromboxane by them. Under the influence of thromboxane, on the contrary, the level of cAMP in platelets decreases.
Intact prostacyclin-producing endothelium does not attract platelets. There are other explanations as well. Endothelial cells and platelets are negatively charged and repel each other. Synthesized by endothelial cells, the so-called endothelium-dependent relaxation factor, like prostacyclin, inhibits platelet adhesion and aggregation. Finally, the ADPase enzyme is localized on the surface of endothelial cells, which destroys the powerful platelet activator ADP (the resulting AMP, on the contrary, inhibits platelet adhesion and aggregation). When a defect is formed in the endothelium (for example, due to atherosclerosis), exposed subendothelial tissues, devoid of these factors, become attractive to platelets.
4. 6. Aspirin as an antithrombotic agent.
Aspirin irreversibly acetylates the COX of platelets, which, being anuclear, are unable to synthesize new molecules of this enzyme, as well as other proteins. As a result, the formation of metabolites by arachidonic acid, including thromboxane, is sharply suppressed in platelets during the entire period of their life (up to 10 days). The irreversibility of COX inhibition is the fundamental difference between aspirin and all other NSAIDs that inhibit COX reversibly. Consequently, they would have to be prescribed much more frequently than aspirin, which is both inconvenient and fraught with complications.
Aspirin causes an antithrombotic effect. How is it achieved? In the circulatory system, aspirin circulates for a short time, therefore, it has relatively little effect on the COX of the vascular wall, where the synthesis of prostacyclin continues. In addition, endothelial cells, unlike platelets, are able to synthesize new COX molecules. But the predominant effect on platelet COX is provided by the use of small doses of aspirin - about 50–325 mg per day once, which is significantly less than the doses used for inflammation (2.0–4.0 g per day), and, naturally, more safely. Aspirin has another useful property: being a vitamin K antagonist, it inhibits the synthesis of the thrombin precursor, the main blood coagulation factor, in the liver.
Unfortunately, a violation of the synthesis of PG, which underlies the therapeutic effect, is also due to the main undesirable effects of aspirin - the formation of stomach ulcers and toxic effects on the kidneys. The reason is that with the blockade of COX, simultaneously with the inhibition of the synthesis of harmful pro-inflammatory PGs, there is a decrease in beneficial PGs, in particular, protecting the gastric mucosa from damaging factors, and primarily from hydrochloric acid produced by the stomach. Naturally, these complications were perceived as inevitable. However, recently, in the course of an in-depth study of the mechanism of action of aspirin, it was found that COX has two isoforms: COX-1 and COX-2. COX-1 is a structural enzyme that synthesizes PGs that regulate the normal (physiological) functions of various cells, while COX-2 is activated by pro-inflammatory stimuli and forms PGs involved in the development of the inflammatory process. This is a clear and far from isolated example when a drug acts as a tool for studying fundamental phenomena.
Aspirin and aspirin-like drugs block both COX-2 and COX-1, which explains the nature of the side effects. The discovery of COX isoforms forms the theoretical basis for the creation of anti-inflammatory drugs of a fundamentally new type - selective COX-2 blockers, and therefore, devoid of their typical severe side effects. And such substances have already been obtained, they are undergoing clinical trials.
In connection with the recent discovery of an anti-proliferative (preventing cell proliferation) effect on the colonic mucosa, the effectiveness of the use of aspirin in the treatment of colon and rectal cancer, whose cells express COX-2, is being intensively studied. Based on the involvement of the inflammatory component in the development of Alzheimer's disease (a variant of the rapid development of dementia in the elderly), the expediency of using NSAIDs in its treatment is being studied.
Considering that the most common side effect of aspirin is damage to the gastric mucosa, it is understandable to try to minimize it. The damaging effect of aspirin on the stomach is realized at two levels: systemic, which has already been mentioned above, and local. The local effect consists in a direct damaging effect on the gastric mucosa, since the substance, poorly soluble in water and acidic stomach contents, is deposited in the folds of the mucous membrane.
The local irritant effect, especially inherent in conventional ASA tablets, can be significantly reduced by coating the tablets with a coating that dissolves only in the intestine. Microencapsulated tablets have a similar effect. True, in this case, the absorption of the drug is delayed, which, however, does not matter for the antiplatelet effect. Soluble tablets, which include special substances that increase the solubility of ASA in water, provide a quick and more pronounced effect while reducing the risk of damage to the stomach. But in the stomach (pH 1.5–2.5), part of the dissolved substance can recrystallize. To prevent this from happening, the tablets include substances with buffer properties - sodium bicarbonate, sodium citrate, etc. ASA complex compounds with good water solubility have been obtained. So, lysine acetylsalicylate (drugs aspizol and laspal) is administered intravenously and intramuscularly. The developed transdermal forms of ASA are very promising - in the form of a patch applied to the skin. Such a dosage form, according to preliminary data, provides not only a long-term intake of the drug into the systemic circulation and a decrease in side effects on the stomach, but also a relatively selective inhibition of platelet COX while maintaining the synthesis of prostacyclin.
5. Pharmacokinetics.
Almost immediately after ingestion of the ACS tablet, the process of transformation into the main metabolite, salicylic acid, begins. Absorption of acetylsalicylic and salicylic acids from the gastrointestinal tract occurs quickly and completely. The maximum level of plasma concentration is reached after 10-20 minutes (acetylsalicylic acid) or after 0.3-2 hours (total salicylate).
The degree of protein binding depends on the concentration and is 49-70% for acetylsalicylic acid, and 66-98% for salicylic acid.
Acetylsalicylic acid is 50% metabolized during the "first pass" through the liver.
The metabolite of acetylsalicylic acid, along with salicylic acid, is glycine conjugate of salicylic acid, gentisic acid and its glycine conjugate.
The drug is excreted as metabolites mainly through the kidneys. The half-life of acetylsalicylic acid is about 20 minutes (increases in proportion to the dose taken and is 2, 4 and 20 hours for doses of 0.5, 1 and 5 g, respectively).
The drug penetrates into breast milk, cerebrospinal fluid, synovial fluid and through the blood-brain barrier.
The anti-inflammatory effect of acetylsalicylic acid occurs after 1-2 days of administration (after the creation of a constant therapeutic level of salicylates in the tissues, which is 150-300 μg / ml), reaches a maximum at a concentration of 20-30 mg% and persists throughout the entire period of application. Acute inflammation is completely suppressed within a few days, with a chronic course, the effect develops over a longer time and is not always complete. Antiaggregatory action (lasts for 7 days after a single dose) is more pronounced in men than in women.
5. 1. Indications.
CHD, presence of several risk factors for CHD, silent myocardial ischemia, unstable angina, myocardial infarction (to reduce the risk of recurrent myocardial infarction and death after myocardial infarction), recurrent transient cerebral ischemia and ischemic stroke in men, prosthetic heart valves (prevention and treatment of thromboembolism) , balloon coronary angioplasty and stent placement (reducing the risk of re-stenosis and treating secondary dissection of the coronary artery), as well as non-atherosclerotic lesions of the coronary arteries (Kawasaki disease), aortoarteritis (Takayasu disease), valvular mitral heart disease and atrial fibrillation, mitral valve prolapse ( prevention of thromboembolism), recurrent pulmonary embolism, pericarditis, Dressler's syndrome, rheumatism, rheumatic chorea, rheumatoid arthritis, progressive systemic sclerosis, infectious-allergic myocarditis, fever in infectious and inflammatory diseases, pulmonary infarction, acute thrombosis phlebitis, thoracic radicular syndrome, lumbago, migraine, headache, neuralgia, other pain syndromes of low and moderate intensity.
5. 2. Contraindications.
Acetylsalicylic acid should not be used in the following cases:
Peptic ulcer of the stomach and duodenum in the acute phase;
Increased tendency to hemorrhage;
kidney disease;
Pregnancy;
Hypersensitivity to acetylsalicylic acid and other salicylates.
As a rule, ACS should not be used or should be used only under the supervision of a physician in the following cases:
Simultaneous treatment with anticoagulants, for example, coumarin derivatives, heparin, with the exception of low-dose heparin therapy;
Glucose-6-phosphate dehydrogenase deficiency syndrome;
Bronchial asthma;
Hypersensitivity to NSAIDs or other allergenic substances;
Chronic or recurrent dyspeptic symptoms, as well as a history of gastric and duodenal ulcers;
Impaired kidney and / or liver function.
5. 3. Drug interaction.
With the combined use of the drug Aspirin and anticoagulants, the risk of bleeding increases.
With the simultaneous use of the drug Aspirin and NSAIDs, the main and side effects of the latter are enhanced.
Against the background of treatment with Aspirin, the side effect of methotrexate is aggravated.
With the simultaneous use of the drug Aspirin and oral hypoglycemic drugs - sulfonylurea derivatives - there is an increase in the hypoglycemic effect.
With simultaneous use with GCS, as well as alcohol consumption, the risk of gastrointestinal bleeding increases.
Aspirin weakens the effect of spironolactone, furosemide, antihypertensives, and anti-gout agents that promote the excretion of uric acid.
The appointment of antacids during treatment with Aspirin (especially at doses of more than 3 g for adults and more than 1.5 g for children) can cause a decrease in the high steady-state level of salicylate in the blood.
5. 4. Side effects.
Acetylsalicylic acid lowers the temperature, reduces local inflammation, anesthetizes. It also thins the blood and is therefore used when there is a risk of blood clots. It has been proven that long-term use of a small dose of acetylsalicylic acid by people prone to diseases of the cardiovascular system significantly reduces the risk of stroke and myocardial infarction. At the same time, the drug is completely devoid of the terrible lack of many painkillers - addiction does not develop to it. It seemed like the perfect drug. Some people are so accustomed to this drug that they take it with or without reason - at the slightest pain or just "just in case".
But in no case should we forget that drugs should not be abused. Like any drug, acetylsalicylic acid is not safe. An overdose can lead to poisoning, manifested by nausea, vomiting, pain in the stomach, dizziness, and in severe cases, to toxic inflammation of the liver and kidneys, damage to the central nervous system (discoordination of movements, confusion, convulsions) and hemorrhages.
If a person takes several medications at the same time, you need to be especially careful. Some drugs are incompatible with each other, and because of this, poisoning can occur. Acetylsalicylic acid increases the toxic effects of sulfonamides, enhances the effect of painkillers and anti-inflammatory drugs such as amidopyrine, butadione, analgin.
This medicine also has side effects. Just like salicylic acid, although to a much lesser extent, it leads to irritation of the mucous membranes of the stomach. To avoid negative effects on the gastrointestinal tract, it is recommended to take this medicine after meals with plenty of fluids. The irritating effect of acetylsalicylic acid enhances wine alcohol.
In many ways, the irritating effect of aspirin is due to its poor solubility. If you swallow a tablet, it is slowly absorbed, an undissolved particle of the substance may “stick” to the mucous membrane for some time, causing irritation. To reduce this effect, simply crush an aspirin tablet into powder and drink it with water, sometimes alkaline mineral water is recommended for this purpose, or buy soluble forms of aspirin - effervescent tablets. However, it should be borne in mind that these measures do not reduce the risk of gastrointestinal bleeding due to the effect of the drug on the synthesis of "protective" prostaglandins in the gastric mucosa. Therefore, it is better not to abuse acetylsalicylic acid, especially for people with gastritis or stomach ulcers.
Sometimes the effect of reducing blood clotting can be undesirable or even dangerous. In particular, preparations containing acetylsalicylic acid are not recommended during the week before surgery, as it increases the risk of unwanted bleeding. Pregnant women and young children should not take acetylsalicylic acid preparations unless absolutely necessary.
The mechanism of action of acetylsalicylic acid is complex and not fully understood, and its properties are still the subject of research by many scientific teams. In 2003 alone, about 4000 scientific articles were published on the intricacies of the physiological action of this substance. On the one hand, scientists are finding new uses for an old drug - for example, recent studies have revealed the mechanism of the effect of acetylsalicylic acid on lowering blood sugar levels, which is important for diabetics. On the other hand, based on research, new drugs of acetylsalicylic acid are being developed, the side effects of which are minimized. Obviously, acetylsalicylic acid will provide work for more than one generation of scientists - physiologists and pharmacists.
5. 5. ACS overdose and first aid.
May occur after a single large dose or with prolonged use. If a single dose is less than 150 mg / kg, acute poisoning is considered mild, 150-300 mg / kg - moderate and severe - at higher doses.
Symptoms: salicylism syndrome (nausea, vomiting, tinnitus, general malaise, fever - a poor prognostic sign in adults). More severe poisoning - stupor, convulsions and coma, non-cardiogenic pulmonary edema, severe dehydration, acid-base balance disorders (first - respiratory alkalosis, then - metabolic acidosis), renal failure and shock. The greatest risk of developing chronic intoxication is observed in the elderly when taken for several days more than 100 mg / kg / day. In children and elderly patients, the initial signs of salicylism are not always noticeable, so it is advisable to periodically determine the concentration of salicylates in the blood. A level above 70 mg% indicates a moderate or severe poisoning above 100 mg% - an extremely severe, unfavorable prognostically. Moderate poisoning requires hospitalization for at least 24 hours.
PMP: provocation of vomiting, the appointment of activated charcoal and laxatives, alkalinization of urine (shown at salicylate levels above 40 mg%, provided by intravenous infusion of sodium bicarbonate - 88 meq in 1 liter of 5% glucose solution, at a rate of 10-15 ml / kg / h), restoration of BCC and induction of diuresis (achieved by the introduction of bicarbonate in the same dose and dilution, repeated 2-3 times) should be borne in mind that intensive fluid infusion in the elderly can lead to pulmonary edema. The use of acetozolamide for alkalization of urine is not recommended (may cause acidemia and increase the toxic effect of salicylates). Hemodialysis is indicated when the level of salicylates is more than 100-130 mg%, and in patients with chronic poisoning - 40 mg% and below if indicated (refractory acidosis, progressive deterioration, severe CNS damage, pulmonary edema and renal failure). With pulmonary edema - IVL with a mixture enriched with oxygen, in the positive pressure mode at the end of exhalation, hyperventilation and osmotic diuresis are used to treat cerebral edema.
Drugs containing ACS:
Agrenox caps. , Alka-Seltzer, Alka-Prim, Antigrippin-ANVI, Askofen-P, Aspicor, Aspirin Cardio
Aspirin-C tab. thorn. , Aspirin, Cardiomagnyl, Cofitsil-plus, Nextrim asset, Terapin, Thrombo ACC, Upsarin UPSA, Citramon.
1. 1. Synthesis of aspirin.
Purpose of work: to obtain acetylsalicylic acid from salicylic acid and acetic anhydride. Carry out the identification of the products obtained during the synthesis.
Progress:
1. 2.5 g of salicylic acid, 3.8 g (3.6 ml) of acetic anhydride and 2-3 drops of concentrated sulfuric acid (H2SO4 conc) were placed in a 50 ml conical flask.
2. The mixture was thoroughly mixed, heated in a water bath to 600C and kept at this temperature for 20 minutes, stirring the liquid.
3. The liquid was then allowed to cool to room temperature. After cooling, the liquid is placed in 40 ml of water, mixed well and the resulting aspirin is filtered on a Schott filter.
4. The resulting product was dried and identified by melting point.
1. 2. Identification.
Conclusion: received aspirin from salicylic acid and acetic anhydride. Identified acetylsalicylic acid by its melting point.
IV. Conclusions.
In this work, I examined the chemical and physical properties of aspirin, the history of its study and discovery, methods of preparation, points of application of ACS and the effect of this drug on the human body.
During the study of acetylsalicylic acid, I came to the conclusion:
1) Aspirin is one of the most effective drugs among salicylates.
2) ACS has such positive effects as: antipyretic, anti-inflammatory, analgesic, antithrombotic, blood thinning, reducing the risk of stroke (heart attack) and blood sugar, and some others.
3) The characteristic side effects of aspirin are: irritation of the mucous membranes of the stomach, a decrease in beneficial PG, impaired liver and kidney function, and others.
4) As a result of prolonged use or after a single dose, an overdose of ACS may occur. In this case, it is necessary to provide first aid: provocation of vomiting, use of activated charcoal or laxatives. It is also recommended to seek help from a specialist.
5) You should be especially careful when using several drugs at once. Aspirin enhances the effect of medications, and is completely incompatible with some!
Also in this work, in a practical way, I received acetylsalicylic acid and carried out its identification by melting point.