The structure and physical and chemical properties of aspirin. Aspirin (acetylsalicylic acid) For fever and pain, for the heart and for children

Acetylsalicylic acid is one of the most famous and widely used medicines in the world. There are more than 50 names - trade marks of drugs, the main active principle of which is this substance. Over 40,000 tons of aspirin are consumed worldwide every year. This unusual drug can be called the record holder among medicines. Acetylsalicylic acid - a long-lived drug in the world, officially celebrated its centenary in 1999, and is still the most popular drug in the world. Despite its advanced age, aspirin is fraught with many mysteries.

Almost every person used this drug at least once in his life, everyone pursued different goals: someone lowered the temperature, someone reduced pain and inflammation, and someone “thinned the blood”.

Each of us has this remedy in our 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 a second episode of vascular accident. According to the Society of Cardiologists of the Nizhny Novgorod Region in 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 primarily to improve the quality of life.

You can still 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, meaningful from a practical and scientific-experimental point of view, and at the same time 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.

Purpose of the work: to prove the universality of application in everyday life.

Objectives: to study the properties of aspirin, to consider the points of application of the drug and the effect of ACS on the human body, to trace its path from discovery to synthesis.

Research methods: analysis of scientific literature and Internet resources, practical work, formulation of conclusions.

1. Structure and physical and 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 known drugs of different chemical structures (for example: ortofen, indomethacin, butadion, etc.).

Acetylsalicylic acid, or aspirin, is an ester formed by acetic and salicylic acid, the latter reacting as phenol in the reaction to form this ester.

2-acetyloxybenzoic acid Gross 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 humid air, it hydrolyzes into acetic and salicylic acids. As a result, pharmacists often have to check to see if the acetylsalicylic acid has 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, readily soluble in 96% alcohol, soluble in ether. Well 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 0С, 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. Add 50.0 ml of 0.5M sodium hydroxide solution, close the flask and incubate for 1 hour. The resulting solution is titrated with 0.5M hydrochloric acid, 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 of C9H8O4.

In acetylsalicylic acid, if it is stored improperly, 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 antipyretic traditional medicine. It contains a bitter-tasting substance called salicylic acid glycoside. It was salicylic acid that became the precursor to aspirin.

As early as 2500–3500 years ago, in ancient Egypt and Rome, the healing properties of willow bark (a natural source of salicylates), as an antipyretic and analgesic agent, were known. 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 as a decoction for fever and labor pains. In the middle of the eighteenth century, the Rev. Edmund Stone, a rural vicar from Oxfordshire, presented to the President of the Royal Society of London a report on the healing of willow bark fever.

And at the beginning of the 18th century, the bark of a tree of "feverish tremors" was brought from Peru to Europe, with which the Indians treated "swamp fever" and which they called kina - kina. The powder of this bark was renamed to “china” and was used for “fevers” and “fevers” of all kinds. But china, and subsequently its active principle, quinine, was expensive, so they were looking for a substitute for it.

In 1828, a professor of chemistry at the University of Munich, Johann Büchner, isolated an active substance from the bark of a willow - a bitter-tasting glycoside, which he named salicin (from the 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 possesses medicinal properties. In fact, this was the first purification of a substance for the further development of acetylsalicylic acid.

The acetyl group (top left) is linked through an oxygen atom (marked in red)

with salicylic acid.

In 1859, professor of chemistry Hermann Kolbe of the University of Marburg discovered the chemical structure of salicylic acid, which made it possible to open the first factory for its production in Dresden in 1874.

However, all of the willow bark therapies existing at that time had a very serious side effect - they caused severe abdominal pain and nausea and were discontinued.

In 1853, French chemist Charles Frédéric Gerard, in the course of experiments, found a way to acetylation of salicylic acid, but did not complete the work. And in 1875, it began to be used for the treatment of rheumatism and sodium salicylate as an antipyretic agent.

Further history is already beginning to bear a detective character, according to the preserved documentation, the immense popularity of sodium salicylate prompted the German chemist Felix Hoffman, who worked at the Bayer enterprise, to continue the research of Charles F. Gerard in 1897. In collaboration with his leader Heinrich Dreser, based on the work of a French chemist, he developed a new method for obtaining the acetylated form of salicylic acid - acetylsalicylic acid, which had all the same therapeutic properties, but was much better tolerated by patients. This discovery may well be called the foundation for the creation of the ASPIRIN® drug.

The story goes that F. Hoffmann's father, a Württemberg manufacturer, suffered from rheumatic pain and could not walk. To reduce the severity of pain, the doctors prescribed him sodium salicylate, but after each intake of this drug, Hoffman Sr. began to vomit. In this regard, Hoffman Jr., on his own initiative, began to work to improve a 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 persist for a long time without losing its therapeutic activity. The industrial production of acetylsalicylic acid began in 1893.

Initially, aspirin was produced as a powder, packaged in glass vials. Tablet production began in 1914.

March 6, 1899 - the day acetylsalicylic acid was registered as a commercial drug called 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 an optimal industrial synthesis developed. The successful memorable commercial name and the conclusion to the over-the-counter group in 1915 led to its widespread distribution and the subsequent scientific search with the creation of a whole group of drugs "NSAIDs". Immediately after its release, the drug gained very great popularity and has not left the shelves of all pharmacies in the world for more than 100 years. Only in the USA, where aspirin for some reason enjoys the special love of the population, it is produced in an 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 actually it is produced by different companies under more than sixty names, which also testifies to its popularity. Initially, ASA was ranked among antipyretic drugs, although it is impossible to explain all its positive properties by a decrease in temperature, in particular in rheumatism. When phenacetin and paracetamol appeared, which lowered the elevated body temperature, but did not have an anti-inflammatory effect, like ASA, then these drugs were considered antipyretic (antipyretics).

Currently, ASA is sold under more than 400 trade names, exists in at least 15 dosage forms and, according to rough estimates, is part of about one and a half thousand combined drugs worldwide. ASA is also the most studied and studied drug currently in use.

3. Getting ACS.

3. 1. Industrial production.

In industry, aspirin is obtained in the course of multistage synthesis from toluene, which in turn is a large-scale industrial product.

Toluene (I) is chlorinated in the presence of a catalyst (AlCl3):

Adduct (II) is oxidized with atomic oxygen (ozone) at a temperature 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 free acid:

Salicylic acid (V) is acylated with acetic anhydride to obtain aspirin (VI):

Al2O3, + (CH3COO) 2H

OH O – C – CH3

(VI) recrystallized from water and sent for packaging.

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 NaOH water CO2

4. Pharmacology.

For many decades, it was believed that aspirin has three main effects: anti-inflammatory, antipyretic, and less pronounced pain relieving.

How are the named effects of aspirin realized or, as drug research experts - pharmacologists say, what are the mechanisms of action? They are complex, interrelated, and still not well understood.

4. 1. Anti-inflammatory effect

It is caused by 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, impairing the energy supply of the inflammatory process (sensitive to a lack of energy), in particular the migration of leukocytes. The stabilizing effect on the membranes of cell lysosomes 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 conversion 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, steric hindrances arise for 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, mainly PGE 2 and PGI 2 are formed. They act on the vascular wall themselves and enhance the influence of other inflammatory mediators: histamine, bradykinin, serotonin.

Recently, it has been established that 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 synthesis (LH) A4 is the acetylation of COX with aspirin. It has been found that lipoxins regulate cellular responses 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

The antipyretic effect, apparently, is also associated with inhibition of the synthesis of PG. NSAIDs, including aspirin, do not affect normal or overheating (heatstroke) body temperature. Other conditions arise with 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 disrupted, which changes the activity of neurons in the thermoregulatory structures of the brain. The consequence is an increase in heat production and a decrease in heat transfer. By suppressing the formation of PGE 2 and thereby restoring the normal activity of neurons, aspirin reduces body temperature. A decrease in temperature occurs due to an increase in heat transfer as a result of vasodilation of the skin, which occurs on command from the center of thermoregulation. At present, based on the concept of the protective role of temperature rise, it is rarely specially reduced. This is usually achieved as a result of influencing the causative factor (the most common situation is the destruction of the causative agent of the infectious process with antibiotics).

However, children are prescribed antipyretic drugs 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 seizures, at a temperature of 37.5–38 ° C. At the same time, it is taken into account that in children with viral infections (influenza, acute respiratory infections, chickenpox), taking aspirin threatens the development of 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 paracetamol.

4. 3. Anesthetic effect

The mechanism of anesthetic (analgesic) action consists of two components: peripheral and central.

It is known that PG (PGE 2, PGF 2a, PGI 2), possessing a moderate intrinsic ability to induce 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 the biosynthesis of PG leads to an increase in the threshold of pain sensitivity, especially during inflammation. The central component, possibly also associated with the inhibition of GHG synthesis, consists in inhibition of the conduction of pain impulses along the ascending nerve pathways, mainly at the level of the spinal cord. In comparison with 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 the PGs themselves is multifaceted, the effect on the formation of which is the main effect of aspirin (and other NSAIDs).

4. 4. Aspirin as an antiplatelet agent for cardiovascular diseases.

The use of aspirin in some cardiovascular diseases, and primarily in ischemic heart disease (IHD), is based on its ability to have an antithrombotic effect, which is expressed in the prevention of blood clots - thrombosis. A thrombus, a blood clot of different density that forms 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 of it. Depending on the degree of ischemia, the possibility of compensating for the deficiency of blood supply at the expense of neighboring vessels, the importance of the organ, the consequences for the body can be different - up to a fatal heart or brain infarction. A thrombus or a fragment of it can break off, move with the blood stream and clog 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 intended only to dissolve an already formed blood clot.

2. Anticoagulants - drugs that reduce blood clotting, used mainly for severe heart disease, because they require careful, weekly monitoring of blood clotting (if the dose is incorrectly selected, dangerous bleeding may occur).

3. Antiplatelet agents (antiplatelet drugs) are the most widely used group of drugs, among which the undisputed leader is our familiar aspirin (acetylsalicylic acid).

In order to understand all the points of application of acetylsalicylic acid in relation to reducing the risk of 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 lymph vessels from the inside. But when the integrity of the endothelial layer is disturbed, they easily adhere to the subendothelial structures, especially to collagen (adhesion), which is ensured by the presence of glycoprotein receptors on the platelet membranes. When this platelets release some substances, including adenosine diphosphate (ADP) and thromboxane, which are powerful aggregates. 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, which activate inactive cells, the mass of platelets increases (the phenomenon of a snowball), and a platelet thrombus occurs. Enzymes, vasoactive peptides, blood clotting factors are released from platelet granules, blood clotting increases, proteins of the coagulation system infiltrate 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, and 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 the well-known messenger (messenger) of signal transmission into the cell - cAMP. Prostacyclin increases the content of cAMP, which keeps 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. On the contrary, under the influence of thromboxane, 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. The so-called endothelium-dependent relaxation factor, synthesized by endothelial cells, 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 formed AMP, on the contrary, inhibits platelet adhesion and aggregation). With the formation of a defect 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 platelet COX, which, being nuclear-free, is unable to synthesize new molecules of this enzyme, like other proteins. As a result, the formation of metabolites by arachidonic acid, including thromboxane, is sharply suppressed in platelets during their entire life cycle (up to 10 days). The irreversible inhibition of COX is the fundamental difference between aspirin and all other NSAIDs, which reversibly inhibit COX. Consequently, they would have to be prescribed much more often than aspirin, which is both inconvenient and fraught with complications.

Aspirin has an antithrombotic effect. How is it achieved? In the circulatory system, aspirin does not circulate for a long 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, of course, is safer. Aspirin has another useful property: being an antagonist of vitamin K, it inhibits the synthesis of the precursor of thrombin, the main factor of blood coagulation, in the liver.

Unfortunately, the main undesirable effects of aspirin - the formation of stomach ulcers and toxic effects on the kidneys - are also caused by the violation of the synthesis of PG, which underlies the therapeutic effect. The reason is that with blockade of COX, simultaneously with inhibition of the synthesis of harmful proinflammatory 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. An illustrative and far from being an isolated example, when a drug acts as a tool for researching 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 antiproliferative (inhibiting cell proliferation) effect on the mucous membrane of the large intestine, the effectiveness of the use of aspirin in the treatment of colon and rectal cancer, whose cells express COX-2, is being intensively investigated. Based on the participation 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.

Given that the most common side effect of aspirin is damage to the gastric mucosa, it is understandable to keep it to a minimum. The damaging effect of aspirin on the stomach is realized at two levels: systemic, which was already 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 the acidic contents of the stomach, is deposited in the folds of the mucous membrane.

The local irritant effect, especially inherent in conventional ASA tablets, can be significantly weakened by coating the tablets with a coating that dissolves only in the intestine. Microencapsulated tablets have a similar effect. True, the absorption of the drug is delayed, which, however, does not matter for the antiplatelet effect. A quick and more pronounced effect while reducing the risk of damage to the stomach is provided by dissolving tablets, which contain special substances that increase the solubility of ASA in water. But in the stomach (pH 1.5–2.5), part of the solute can recrystallize. To prevent this from happening, the tablets include substances with buffer properties - sodium bicarbonate, sodium citrate, and others. Complex compounds of ASA 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 prostacyclin synthesis.

5. Pharmacokinetics.

Almost immediately after ingestion of the ACS tablet, the process of transformation into the main metabolite, salicylic acid, begins. The absorption of acetylsalicylic and salicylic acids from the gastrointestinal tract occurs quickly and completely. The maximum level of concentration in blood plasma 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 the 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 passes 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 lasts the entire period of use. Acute inflammation is completely suppressed within a few days; in a chronic course, the effect develops over a longer time and is not always complete. The antiaggregatory effect (lasts for 7 days after a single dose) is more pronounced in men than in women.

5. 1. Indications.

Ischemic heart disease, presence of several risk factors for ischemic heart disease, painless myocardial ischemia, unstable angina pectoris, myocardial infarction (to reduce the risk of recurrent myocardial infarction and death after myocardial infarction), repeated transient cerebral ischemia and ischemic stroke in men, heart valve replacement (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 for non-atherosclerotic lesions of the coronary arteries (Kawasaki disease), aortoarteritis (Takayasu's disease), mitral valvular 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 phlebitis, chest radicular syndrome, lumbago, migraine, headache, neuralgia, other pain syndromes of mild and moderate intensity.

5. 2. Contraindications.

Acetylsalicylic acid should not be used in the following cases:

Peptic ulcer and duodenal ulcer 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 medical supervision 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;

Dysfunction of the kidneys and / or liver.

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 the drug Aspirin, the side effect of methotrexate is aggravated.

With the simultaneous use of the drug Aspirin and oral hypoglycemic drugs - sulfonylurea derivatives - the hypoglycemic effect is enhanced.

With simultaneous use with GCS, as well as alcohol consumption, the risk of gastrointestinal bleeding increases.

Aspirin weakens the effect of spironolactone, furosemide, antihypertensive drugs, as well as anti-gout drugs that promote the excretion of uric acid.

Prescribing antacids during treatment with Aspirin (especially in doses of more than 3 g for adults and more than 1.5 g for children) can cause a decrease in the high stable level of salicylate in the blood.

5. 4. Side effects.

Acetylsalicylic acid lowers the temperature, reduces local inflammatory processes, and relieves pain. It also thins the blood and therefore is used when there is a risk of blood clots. It has been proven that long-term intake 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 absolutely devoid of the terrible lack of many painkillers - addiction does not develop to it. It would seem to be the perfect medicine. Some people are so used 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. As with any medicine, acetylsalicylic acid is not safe. Overdose can lead to poisoning, manifested by nausea, vomiting, stomach pain, dizziness, and in severe cases - to toxic inflammation of the liver and kidneys, damage to the central nervous system (disorder of coordination of movements, confusion, convulsions) and hemorrhages.

If a person is taking several medications at the same time, you need to be especially careful. Some medicines are incompatible with each other, and poisoning can occur due to this. 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 irritant effect of acetylsalicylic acid is enhanced by tartaric alcohol.

Much of the irritating effect of aspirin is due to its poor solubility. If you swallow a pill, it is slowly absorbed, an undissolved particle of the substance can "stick" to the mucous membrane for a while, causing irritation. To reduce this effect, it is enough just to 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 may be undesirable or even dangerous. In particular, preparations containing acetylsalicylic acid are not recommended to be taken within a 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 research teams. In 2003 alone, about 4000 scientific articles were published on the intricacies of the physiological action of this substance. Scientists, on the one hand, are finding new uses for the old medicine - for example, recent studies have revealed the mechanism of the effect of acetylsalicylic acid on lowering blood sugar levels, which is important for diabetic patients. On the other hand, based on research, new drugs for acetylsalicylic acid are being developed, the side effects of which are minimized. Obviously, acetylsalicylic acid will provide jobs for more than one generation of scientists - physiologists and pharmacists.

5. 5. Overdose of ACS and first aid.

May occur after a single high dose intake 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 - when using higher doses.

Symptoms: salicylism syndrome (nausea, vomiting, tinnitus, general malaise, fever - a poor prognostic sign in adults). More severe poisoning - stupor, convulsions and coma, noncardiogenic 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, therefore it is advisable to periodically determine the concentration of salicylates in the blood. A level above 70 mg% indicates moderate or severe poisoning above 100 mg% - extremely severe, prognostically unfavorable. In case of moderate poisoning, hospitalization is necessary for at least 24 hours.

PMP: provocation of vomiting, the appointment of activated charcoal and laxatives, alkalinization of urine (shown when the level of salicylates is 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 the BCC and induction of diuresis (achieved by introducing bicarbonate in the same dose and dilution, repeated 2-3 times), it should be borne in mind that intensive fluid infusion in the elderly can lead to pulmonary edema. The use of acetozolamide for alkalizing urine is not recommended (it can cause acidemia and increase the toxic effect of salicylates). Hemodialysis is indicated when the salicylate level is more than 100-130 mg%, and in patients with chronic poisoning - 40 mg% or less if indicated (refractory acidosis, progressive deterioration of the condition, severe damage to the central nervous system, pulmonary edema and renal failure). With pulmonary edema - mechanical ventilation with a mixture enriched with oxygen, in the mode of positive pressure at the end of expiration, hyperventilation and osmotic diuresis are used to treat cerebral edema.

Preparations containing ACS:

Agrenox caps. , Alka-seltzer, Alka-Prim, Antigrippin-ANVI, Askofen-P, Aspikor, Aspirin Cardio

Aspirin -C tab. Thorn. , Aspirin, Cardiomagnil, Kofitsil-plus, Nextrim aktiv, Terapin, Thrombo ASS, Upsarin UPSA, Citramon.

1. 1. Synthesis of aspirin.

Purpose of work: to obtain acetylsalicylic acid from salicylic acid and acetic anhydride. Identify the products obtained during the synthesis.

Progress:

1. In a conical flask with a volume of 50 ml was placed 2.5 g of salicylic acid, 3.8 g (3.6 ml) of acetic anhydride and 2-3 drops of concentrated sulfuric acid (H2SO4conc).

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. Then the liquid was allowed to cool at room temperature. After cooling, the liquid was placed in 40 ml of water, mixed well, and the resulting aspirin was filtered on a Shot filter.

4. The resulting product was dried and identified by its melting point.

1. 2. Identification.

Conclusion: I got aspirin from salicylic acid and acetic anhydride. Performed the identification of 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 production, points of application of the 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 levels, and some others.

3) Typical side effects of aspirin are: irritation of the mucous membranes of the stomach, a decrease in useful 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, the 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 obtained acetylsalicylic acid and carried out its identification by its melting point.

In medical practice, there are several centuries-old drugs that have firmly retained their place in the "gold fund" of drugs. One of these drugs, of course, is aspirin (ASA, acetylsalicylic acid), the 100th anniversary of the creation of which the German company Bayer was celebrated in 1999.

Aspirin is one of the most widely used medicines in the world. Currently, more than 100 different pain relievers are offered in Russia, and almost all of them contain aspirin as the main ingredient.

Indications for the use of ASA in recent years have expanded significantly, the antithrombotic effect comes to the fore:

Aspirin has to be taken for life by patients with prosthetic heart valves in order to prevent thrombosis in the area of ​​artificial valves, after coronary artery bypass grafting in ischemic heart disease, to prevent recurrent myocardial infarction, in patients with transient disorders

cerebral blood supply for the prevention of ischemic stroke

At least 4.5 million people take aspirin at least once a week, and 500,000 take more than 5 tablets a week. The total production of aspirin in the world is thousands of tons per year. In 1994, 11,600 tons of aspirin were consumed worldwide, or about 30 therapeutic doses per person per year.

The history of aspirin began about 4000 years ago. Egyptian papyri that date from about 1550 BC mention the use of a decoction of white willow leaves for many diseases. Hippocrates (460-377 BC) recommended juice prepared from the bark of the same tree for the treatment of pain and fever. The medicinal effect of willow in medicine was also well known in America (before its "discovery" by Columbus). Willow is the first source of aspirin. By the middle of the 18th century. Willow bark was already a well-known folk remedy for the treatment of colds.

In 1757, the priest E. Stone from Oxfordshire (Great Britain), became interested in the extreme bitterness of willow bark, similar in taste to cinchona made from cinchona bark, a rare and expensive remedy for the treatment of malaria.

On June 2, 1763, speaking before the Royal Society, Stone, based on the results of his research, substantiated the use of willow bark infusion for diseases accompanied by a febrile state.

More than half a century later, intensive research began on the active principle of the willow bark. In 1829, the French pharmacist Pierre-Joseph Leroux obtained a crystalline substance from the willow bark, which he called salicyl (this name comes from the Latin name "salix" - the name of the plant first mentioned in the works of the Roman encyclopedic scientist Varro (116-27 BC) BC) and related to willow (willow, willow), The content of salicin in willow is about 2% by dry weight .. In 1838-1839, the Italian scientist R. Piria cleaved salicil, showing that this compound is a glycoside, and, having oxidized its aromatic fragment, obtained a substance that was called salicylic acid.

Salicil was first produced commercially from purified willow bark waste from the basket industry in Belgium, and this small amount of salicin met current needs. However, already in 1874 the first large factory for the production of synthetic salicylates was founded in Dresden.

In 1888, a pharmaceutical department was created at Bayer, which had previously only been involved in the production of aniline dyes, and the company was one of the first to enter the pharmaceutical production process.

The cheapness of salicylic acid allowed it to be widely used in medical practice, but treatment with this drug was fraught with many dangers associated with its toxic properties. The toxicity of salicylic acid was the reason that led to the discovery of aspirin ..

At Bayer's employee Felix Hoffmann (1868-1946), an elderly father suffered from arthritis but could not tolerate sodium salicylates due to chronic acute stomach irritation. A caring son-chemist in the chemical literature found data on acetylsalicylic acid,. which was synthesized 30 years earlier by Charles Gerhardt in 1853 and had less acidity ..

October 10, 1897 F. Hoffman described a method for producing almost pure acetylsalicylic acid (ASA) and its tests revealed high pharmacological activity. Acetylsalicylic acid was found to be tastier and less irritating.

The new drug was given the name "aspirin", taking the letter "a" from the word "acetyl" (acetyl) and part of "spirin" from the German word "Spirsaure", which in turn came from the Latin name of the meadowsweet (Spiraea ulmaria) - a plant containing large amounts of salicylic acid.

In 1899, Bayer began manufacturing a drug called aspirin as an analgesic, antipyretic and pain reliever.

Over the course of a century, Bayer chemists, as well as other researchers, have made numerous attempts to study the effect of structural changes in salicylic acid derivatives on their activity, and thus find compounds that are superior to aspirin. Investigated the influence of the chain length of the acyl group of aspirin, and various substituents in the cycle. Studied various salts of aspirin - calcium, sodium, lithium, as well as lysine acetylsalicylate, which are better soluble in water than acetylsalicylic acid itself.

The presence of an acetyl group in aspirin is a condition for pharmaceutical action. (The molecular basis of the mechanism of action is studied in the course of biochemistry)

Some of the above compounds were introduced into medical practice, and although some drugs had an advantage over aspirin (especially in the treatment of rheumatism), none of them has ever gained such widespread popularity.

Structural formula

True, empirical, or gross formula: C 9 H 8 O 4

Chemical composition of Acetylsalicylic acid

Molecular mass: 180.159

Acetylsalicylic acid(colloquial aspirin; Latin Acidum acetylsalicylicum, salicylic ester of acetic acid) is a drug that has analgesic (pain relieving), antipyretic, anti-inflammatory and antiplatelet effect. The mechanism of action and safety profile of acetylsalicylic acid are well studied, its effectiveness has been clinically tested, and therefore this drug is included in the list of essential medicines of the World Health Organization, as well as in the list of vital and essential medicines of the Russian Federation. Acetylsalicylic acid is also widely known under the trademark Aspirin, patented by Bayer.

Story

Traditional medicine has long recommended the bark of young white willow branches as an antipyretic agent, for example, for preparing a decoction. The cortex also received recognition from doctors under the name Salicis cortex. However, all of the existing willow bark therapies had a very serious side effect - they caused severe abdominal pain and nausea. In a stable form suitable for purification, salicylic acid was first isolated from willow bark by the Italian chemist Rafel Piria in 1838. It was first synthesized by Charles Frederic Gerard in 1853. In 1859, professor of chemistry Hermann Kolbe from the University of Marburg discovered the chemical structure of salicylic acid, which made it possible in 1874 to open the first factory for its production in Dresden. In 1875, sodium salicylate was used to treat rheumatism and as an antipyretic agent. Soon, its glucosuric effect was established, and salicin began to be prescribed for gout. On August 10, 1897, Felix Hoffman of Bayer AG laboratories first obtained samples of acetylsalicylic acid in a form that could be used for medical purposes; using the acetylation method, he became the first chemist in history who managed to obtain salicylic acid in a chemically pure and stable form. Along with Hoffman, Arthur Eichengrün is also called the inventor of aspirin. The raw material for the production of acetylsalicylic acid was the bark of a willow tree. Bayer has registered a new drug under the brand name aspirin. Hoffman discovered the medicinal properties of acetylsalicylic acid while trying to find a cure for his rheumatic father. In 1971, pharmacologist John Wayne demonstrated that acetylsalicylic acid suppresses the synthesis of prostaglandins and thromboxanes. For this discovery in 1982 he, as well as Sune Bergström and Bengt Samuelson, were awarded the Nobel Prize in Medicine; in 1984 he was awarded the title of Knight Bachelor.

Trade name Aspirin

After long disputes, it was decided to take as a basis the already mentioned Latin name of the plant, from which the Berlin scientist Karl Jakob Lovig first isolated salicylic acid - Spiraea ulmaria. The four letters "spir" were assigned "a" to emphasize the special role of the acetylation reaction, and on the right - for euphony and in accordance with the established tradition - "in". The result is a simple pronunciation and easy to remember name Aspirin. Already in 1899, the first batch of this drug appeared on the market. Initially, only the antipyretic effect of aspirin was known, later its analgesic and anti-inflammatory properties were also revealed. In the early years, aspirin was sold as a powder, and from 1904 in pill form. In 1983, a study was published in the New England Journal of Medicine, which proved a new important property of the drug - when it is used during unstable angina pectoris, the risk of such an outcome of the disease as myocardial infarction or death is halved. Acetylsalicylic acid also reduces the risk of developing cancer, particularly of the breast and colon.

Mechanism of action

Suppression of the synthesis of prostaglandins and thromboxanes. Acetylsalicylic acid is an inhibitor of cyclooxygenase (PTGS), an enzyme involved in the synthesis of prostaglandins and thromboxanes. Acetylsalicylic acid works like other non-steroidal anti-inflammatory drugs (notably diclofenac and ibuprofen), which are reversible inhibitors. Thanks to the remark of the Nobel laureate John Wayne, which he expressed as a hypothesis in one of his articles, it was long believed that acetylsalicylic acid acts as a suicidal inhibitor of cyclooxygenase, acetylating the hydroxyl group in the active center of the enzyme. Further research has shown that this is not the case.

pharmachologic effect

Acetylsalicylic acid has anti-inflammatory, antipyretic and analgesic effects, and it is widely used for fever, headache, neuralgia, etc., and as an antirheumatic agent. The anti-inflammatory effect of acetylsalicylic acid (and other salicylates) is explained by its effect on the processes occurring in the focus of inflammation: a decrease in capillary permeability, a decrease in hyaluronidase activity, a limitation of the energy supply of the inflammatory process by inhibiting the formation of ATP, etc. In the mechanism of anti-inflammatory action, the inhibition of biosynthesis is important. The antipyretic effect is also associated with the effect on the hypothalamic centers of thermoregulation. The analgesic effect is due to the effect on the centers of pain sensitivity, as well as the ability of salicylates to reduce the algogenic effect of bradykinin. The blood thinning effect of acetylsalicylic acid makes it possible to use it to reduce intracranial pressure in case of headaches. Salicylic acid served as the basis for a whole class of medicinal substances called salicylates, an example of such a drug is dioxybenzoic acid.

Application

Acetylsalicylic acid is widely used as an anti-inflammatory, antipyretic and analgesic agent. It is used alone and in combination with other drugs. There are a number of finished medicines containing acetylsalicylic acid (tablets "Citramon", "Kofitsil", "Asfen", "Askofen", "Acelizin", etc.). Recently, injectable preparations have been obtained, the main active principle of which is acetylsalicylic acid (see Acelizin, Aspizol). In the form of tablets, acetylsalicylic acid is prescribed orally after meals. The usual doses for adults as an analgesic and antipyretic agent (for febrile diseases, headache; migraine, neuralgia, etc.) 0.25-0.5-1 g 3-4 times a day; for children, depending on age, from 0.1 to 0.3 g per dose. For rheumatism, infectious-allergic myocarditis, rheumatoid arthritis, it is prescribed for a long time to adults, 2-3 g (less often 4 g) per day, to children 0.2 g per year of life per day. A single dose for children aged 1 year is 0.05 g, 2 years old - 0.1 g, 3 years old - 0.15 g, 4 years old - 0.2 g. Starting from 5 years old, it can be prescribed in tablets of 0 , 25 g per admission. Acetylsalicylic acid is an effective, readily available agent that is widely used in outpatient practice. It should be borne in mind that the use of the drug should be carried out with the observance of precautions due to the possibility of a number of side effects. Many cases have been described where the ingestion of even 40 grams of ethanol (100 grams of vodka) in combination with such conventional drugs as aspirin or amidopyrin, was accompanied by severe allergic reactions, as well as gastric bleeding. The use of acetylsalicylic acid in everyday life is widespread, as a means to relieve suffering the next morning after alcohol poisoning (to relieve a hangover). It is an integral component of the well-known drug "Alka-Seltzer". According to research by Professor Peter Rothwell (University of Oxford), based on an analysis of the health of 25,570 patients, regular intake of acetylsalicylic acid reduces the 20-year risk of prostate cancer by about 10%, lung cancer by 30%, and bowel cancer - by 40%, cancer of the esophagus and throat - by 60%. Regular intake of acetylsalicylic acid for more than 5 years at a dose of 75 to 100 mg reduces the risk of colorectal cancer by up to 16%.

Antiplatelet action

An important feature of acetylsalicylic acid is its ability to have an antiplatelet effect, that is, to prevent spontaneous and induced platelet aggregation. Substances that have an antiplatelet effect are widely used in medicine to prevent the formation of blood clots in people who have had myocardial infarction, cerebrovascular accident, other manifestations of atherosclerosis (for example, exertional angina, intermittent claudication), as well as with a high cardiovascular risk. The risk is considered “high” when the risk of non-fatal myocardial infarction or death due to heart disease in the next 10 years is more than 20%, or the risk of dying from any cardiovascular disease (including stroke) in the next 10 years is more than 5%. With bleeding disorders, such as hemophilia, the possibility of bleeding increases. Acetylsalicylic acid, as a means of primary prevention of complications of atherosclerosis, can be effectively used at a dose of 75-100 mg / day, this dose is well balanced in the ratio of effectiveness / safety. Acetylsalicylic acid is the only antiplatelet drug, the effectiveness of which, when administered in the acute period of ischemic stroke, is supported by evidence-based medicine. In the course of studies, a tendency towards a decrease in mortality was demonstrated both during the first 10 days and within 6 months after ischemic stroke, in the absence of pronounced hemorrhagic complications.

Side effect

Safe daily dose of acetylsalicylic acid: 4 g. Overdose leads to severe pathologies of the kidneys, brain, lungs and liver. Medical historians believe that the massive use of acetylsalicylic acid (10-30 g each) significantly increased mortality during the 1918 influenza pandemic. When using the drug, profuse sweating may also develop, tinnitus and hearing loss, angioedema, skin and other allergic reactions may appear. The so-called ulcerogenic (causing the appearance or exacerbation of gastric and / or duodenal ulcers) action is characteristic to one degree or another of all groups of anti-inflammatory drugs: both corticosteroid and non-steroidal (for example, butadione, indomethacin, etc.). The appearance of stomach ulcers and gastric bleeding with the use of acetylsalicylic acid is explained not only by the resorptive effect (inhibition of blood coagulation factors, etc.), but also by its direct irritating effect on the gastric mucosa, especially if the drug is taken in the form of uncrushed tablets. This also applies to sodium salicylate. With prolonged, without medical supervision, the use of acetylsalicylic acid, side effects such as dyspeptic disorders and gastric bleeding can be observed. To reduce the ulcerogenic effect and gastric bleeding, acetylsalicylic acid (and sodium salicylate) should be taken only after meals, the tablets are recommended to be thoroughly crushed and washed down with plenty of liquid (preferably milk). There is, however, evidence that stomach bleeding can also be observed when taking acetylsalicylic acid after meals. Sodium bicarbonate promotes a more rapid release of salicylates from the body, however, to reduce the irritating effect on the stomach, they resort to taking mineral alkaline waters or sodium bicarbonate solution after acetylsalicylic acid. Abroad, acetylsalicylic acid tablets are produced in an enteric (acid-resistant) shell in order to avoid direct contact of ASA with the stomach wall. With prolonged use of salicylates, the possibility of anemia should be taken into account and systematic blood tests should be performed and the presence of blood in the stool should be checked. Due to the possibility of allergic reactions, care should be taken when prescribing acetylsalicylic acid (and other salicylates) to persons with hypersensitivity to penicillins and other "allergenic" drugs. With increased sensitivity to acetylsalicylic acid, aspirin asthma may develop, for the prevention and treatment of which methods of desensitizing therapy have been developed using increasing doses of acetylsalicylic acid. It should be borne in mind that under the influence of acetylsalicylic acid, the effect of anticoagulants (coumarin derivatives, heparin, etc.), sugar-lowering drugs (sulfonylurea derivatives) increases, the risk of gastric bleeding increases with the simultaneous use of corticosteroids and non-steroidal anti-inflammatory drugs (NSAIDs), side effects of methotrexate increase. The effect of furosemide, uricosuric agents, spironolactone is somewhat weakened.

In children and pregnant women

In connection with the available experimental data on the teratogenic effect of acetylsalicylic acid, it is not recommended to prescribe it and preparations containing it to women in the first 3 months of pregnancy. Taking non-narcotic pain relievers (aspirin, ibuprofen, and paracetamol) during pregnancy increases the risk of genital disorders in newborn boys in the form of cryptorchidism. The results of the study showed that the simultaneous use of two of the three listed drugs during pregnancy increases the risk of having a baby with cryptorchidism up to 16 times compared with women who did not take these drugs. Currently, there is evidence of the possible danger of using acetylsalicylic acid in children for the purpose of lowering the temperature with influenza, acute respiratory and other febrile diseases in connection with the observed cases of Reye's syndrome (Reye) (hepatogenic encephalopathy). The pathogenesis of the development of Reye's syndrome is unknown. The disease proceeds with the development of acute liver failure. The incidence of Reye's syndrome among children under 18 years of age in the United States is approximately 1 in 100,000, with a case fatality rate exceeding 36%.

Contraindications

Peptic ulcer and duodenal ulcer and bleeding are contraindications to the use of acetylsalicylic acid and sodium salicylate. The use of acetylsalicylic acid is also contraindicated in case of a history of peptic ulcer disease, with portal hypertension, venous stasis (due to a decrease in the resistance of the gastric mucosa), and in violation of blood coagulation. Acetylsalicylic acid preparations should not be prescribed to children under 12 years of age to lower body temperature in viral diseases due to the possibility of Reye's syndrome. It is recommended to replace acetylsalicylic acid with paracetamol or ibuprofen. Some people may experience so-called aspirin asthma.

Substance properties

Acetylsalicylic acid is a white fine needle-like crystals or light crystalline powder of slightly acidic taste, slightly soluble in water at room temperature, soluble in hot water for 30 minutes. After cooling. Acetylsalicylic acid, when heated above 200 degrees Celsius, becomes an extremely active flux that dissolves oxides of copper, iron and other metals. in the presence of sulfuric acid. The product is recrystallized for purification. The yield is about 80%.

Facts

• In Russia, the traditional household name for acetylsalicylic acid is aspirin. Based on the tradition of the term, Bayer was denied registration of the aspirin brand in Russia.
• More than 80 billion aspirin tablets are consumed annually.
• In 2009, researchers discovered that salicylic acid, which is derived from acetylsalicylic acid, can be produced by the human body.
• Acetylsalicylic acid is used as an active acid flux for brazing and tinning with low-melting alloys.
• Scientists have found that aspirin can help treat many cases of infertility in women. it counteracts the inflammation caused by the protein that is high in miscarriages. Women can increase their chances of getting pregnant by taking limited doses of aspirin.

municipal educational institution

secondary school number 29

Traktorozavodsky district of Volgograd

City competition

teaching and research

works of high school students

"I and the Earth"

them. IN AND. Vernadsky

(chemistry section)

RESEARCH

ON THE TOPIC OF:

"Study of the properties of aspirin and its effect on the human body."

Completed:

11th grade students

MOU SOSH №29

Gulina Victoria,

Nikiforov Dmitry

Supervisor:

chemistry teacher MOU SOSH №29

Travina Maria Evgenievna.

Volgograd - 2015

TABLE OF CONTENTS.

INTRODUCTION __________________________________________________ 3

CHAPTER 1. Literature review ___________________________________ 5

1.1. The history of aspirin _________________________ ________5

1.2. Pharmacological action of aspirin ______________________ 8

1.3. Chemical properties of acetylsalicylic acid ____________10

CHAPTER 2. Experimental ____________________________ 12

2.1. Study of the solubility of aspirin in water ____________________12

2.2. Determination of pH of solutions containing acetylsalicylic acid _________________________________________________________13

2.3. Determination of the solubility of aspirin in ethyl alcohol ______ 14

2.4. Determination of phenol derivative in solution _________________15

2.5. Studying the effect of aspirin on the growth of molds ______16

CONCLUSION _____________________________________________ 17

REFERENCES ______________________________________________ 18

Introduction.

Acetylsalicylic acid is one of the most famous and widely used medicines in the world. There are more than 50 names - trade marks of drugs, the main active principle of which is this substance. Over 40,000 tons of aspirin are consumed worldwide every year. This unusual drug can be called the record holder among medicines. Acetylsalicylic acid - a long-lived drug in the world, officially celebrated its centenary in 1999, and is still the most popular drug in the world.

Almost every person has used this medicine at least once in his life. Initially, this drug was intended to lower body temperature, then several more effects were found: such as pain reliever, 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 with the use of drugs lies in the rationality and literacy of their use.

Object of study: medicinal products containing acetylsalicylic acid.

Subject of study: physicochemical and pharmacological properties of aspirin.

Objective:

to study the characteristic physical and chemical properties, mechanism of action and methods of safe use of drugs containing acetylsalicylic acid.

To achieve this goal, the following were formulated tasks:

read the literature containing information about acetylsalicylic acid;

conduct chemical experiments proving the properties of acetylsalicylic acid;

find out the effect of acetylsalicylic acid on the human body;

experimentally test the suppression of the growth of mold fungi on food with the help of acetylsalicylic acid.

Chapter 1. Literature review.

1.1. The history of the creation of aspirin.

The history of the drug Aspirin is one of the longest and most beautiful in pharmacology. As early as 2500–3500 years ago, in ancient Egypt and Rome, the healing properties of willow bark, a natural source of salicylates, as an antipyretic and analgesic agent, were known. On papyri dating from the 2nd millennium BC, found by the German Egyptologist Georg Ebers among 877 other medical recipes, recommendations for the use of myrtle leaves (also containing salicylic acid) for rheumatic pain and radiculitis are described. About a thousand years later, the father of medicine Hippocrates, in his instructions, recommended the use of willow bark as a decoction for fever and labor pains. In the middle of the eighteenth century. The Rev. Edmund Stone, a rural vicar from Oxfordshire, presented to the President of the Royal Society of London a report on the healing of willow bark fever. Often for anesthesia, 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 begin serious research on the composition of medicinal products from plant materials.

So, in 1828, professor of chemistry at the University of Munich Johann Büchner isolated an active substance from the bark of a willow - a bitter-tasting glycoside, which he named salicin (from the 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 further development of the drug.

In 1859, chemistry professor Hermann Kolbe of the University of Marburg discovered the chemical structure of salicylic acid, which made it possible to open the first factory for its production in Dresden in 1874.

However, all of the willow bark therapies available at that time had a very serious side effect - they caused severe abdominal pain and nausea.

In 1853, the French chemist Charles Frédéric 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 agent.

The immense popularity of sodium salicylate awakened the German chemist Felix Hoffman, who worked at the Bayer enterprise, in 1897 to continue the research of Sh.F. Gerard. In collaboration with his leader Heinrich Dreser, based on the work of a French chemist, he developed a new method for obtaining the acetylated form of salicylic acid - acetylsalicylic acid, which had all the same therapeutic properties, but was much better tolerated by patients. This discovery may well be called the foundation for the creation of the drug.

To assess the safety of the resulting drug, the first preclinical experimental studies in animals in the world history were carried out. Thus, the study of the pharmacological properties of the drug was the beginning of clinical trials of drugs, which from 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 proven and it was recommended for therapeutic use.

March 6, 1899, when the 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.

For more than 100 years of its active medical use, Aspirin not only has not lost its relevance, but has also expanded its scope in such diverse areas as the elimination of pain, cold symptoms, as well as in the prevention of cardiovascular diseases.

Scientific interest in the drug is inexhaustible.

1.2. Pharmacological action of aspirin.

Acetylsalicylic acid has anti-inflammatory, antipyretic and analgesic effects; it is widely used for fevers, headaches, neuralgia, and also as an antirheumatic agent.

The anti-inflammatory effect of acetylsalicylic acid is explained by its effect on the processes occurring in the focus of inflammation: 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. In the mechanism of anti-inflammatory action, inhibition of prostaglandin biosynthesis is important.

The blood thinning effect of aspirin makes it possible to use it to reduce intracranial pressure, in case of the risk of blood clots. It has been proven that long-term intake 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.

As with any medicine, 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 is taking several medications at the same time, you need to be especially careful. Some medicines are incompatible with each other, and poisoning can occur due to this. 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 irritates the stomach lining. 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 fine needle-like crystals or light crystalline powder of slightly acidic taste.

The full chemical name of acetylsalicylic acid is 2-acetoxy-benzoic acid

Physicochemical characteristics

Short chemical formula: C9H8O4

Molecular mass: 180.2

Melting point: 133 - 138 0 С

Dissociation constant:pKa = 3.7

Acetylsalicylic acid is produced by heating salicylic acid with acetic anhydride:

When acetylsalicylic acid decomposes into acetic acid. Hydrolysis is carried out by boiling a solution of acetylsalicylic acid in water for 30 seconds. After cooling, salicylic acid, poorly soluble in water, precipitates in the form of fluffy needle-like crystals.

When heated with sodium hydroxide in an aqueous solution, acetylsalicylic acid is hydrolyzed to sodium salicylate and sodium acetate.

One part of acetylsalicylic acid dissolves in:

300 parts of water

20 parts of ether

17 parts 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 purchased at the pharmacy containing acetylsalicylic acid: "Upsarin upsa", "Aspirin - C", "Acetylsalicylic acid".

Research method: pounded pills of each medicine in a mortar. Designated test tubes

№ 1 - ASPIRIN - C

№ 2 - UPSARIN UPSA

№ 3 - ACETYLALICYLIC ACID

Transferred into tubes, 0.1 g of each drug. Added to each tube 10 ml of water and noted the solubility of drugs in water. The test tubes with substances were heated on an alcohol lamp.

Conclusions:

Test tube No. 1 - ASPIRIN - C - good solubility;

Test tube No. 2 - UPSARIN UPSA - good solubility;

Test tube No. 3 - ACETYLACYLIC ACID - poor solubility.

Acetylsalicylic acid, according to its physical properties, is slightly soluble in cold water. But Aspirin - C and Upsarin UPSA dissolve well 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 it gets into 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 pH of solutions containing acetylsalicylic acid.

Research method: The pH of the solutions under study in three test tubes was checked using a universal indicator paper.

Conclusions:

Test tube No. 1 - ASPIRIN - С - pH = 5

Test tube No. 2 - UPSARIN UPSA - pH = 7

Test tube No. 3 - ACETYLACYLIC ACID - pH = 3

Acetylsalicylic acid in test tube # 3 showed increased acidity. There is a certain concentration of its own hydrochloric acid in the stomach, 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 method: introduced into test tubes 0.1 g of drugs and added 10 ml of ethanol. The test tubes with substances were heated on an alcohol lamp.

Conclusions:

The results of the experiment showed that ASPIRIN in test tube No. 3 dissolves better 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, as well as a white precipitate, we observed in test tube No. 2 containing UPSARIN UPSA.

The instructions of the manufacturers of aspirin indicate that its use in conjunction with ethanol is unacceptable, this has also been proven by our studies, which have shown 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 phenol derivative (salicylic acid) in solution.

Research method: shaken 0.1 g of each preparation with 10-15 ml of water and added a few drops of iron (III) chloride. When it is added to the solution, a violet color appears.

Conclusions:

Test tube No. 1 - ASPIRIN - C - brown-violet staining

Test tube No. 2 - UPSARIN UPSA - brown staining

Test tube No. 3 - ACETYLACYLIC ACID - purple staining

As a result, it was revealed 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 ACETYLALICYLIC ACID, on the contrary, more phenol derivatives are formed than acetic acid.

A phenol derivative is a very dangerous substance for human health, perhaps it is this that affects the appearance of side effects when taking acetylsalicylic acid.

2.5. Study of the effect of aspirin on the growth of molds.

Research method: place pieces of bread on 4 glasses, designate 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 ACETYL SALICYLIC 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 acetylsalicylic acid solutions were added, mold was not observed.

Conclusions:

Acetylsalicylic acid, even in a low concentration, prevents the growth of molds, as well as some bacteria. Therefore, they are used in large quantities for food preservation. The advantage of this substance is its low toxicity and the fact that it has almost no taste.

Conclusion.

In preparation for the research, a literature review was carried out containing information on acetylsalicylic acid, its properties and application.

In the course of the experiments, the chemical properties of acetylsalicylic acid, as well as its effect on the human body, were proved.

The results of the experiments showed that aspirin is slightly soluble in water, ethyl alcohol, some varieties of the drug have increased acidity and a high content of phenol derivatives.

The danger of aspirin is 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 must carefully read the instructions, as inept use or storage can 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.

Great encyclopedia. Cyril and Methodius 2005 CD - disk.

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 Handbook: Medicines in Russia: Handbook.- M .: Astra-PharmServis.- 2001.

Shulpin G.B. This is a fascinating chemistry. M .; Chemistry, 1984.

Instructions for use:

Acetylsalicylic acid is a drug with a pronounced anti-inflammatory, antipyretic, analgesic and antiplatelet (reduces the clumping process of platelets) effect.

pharmachologic effect

The mechanism of action of acetylsalicylic acid is due to its ability to inhibit the synthesis of prostaglandins, which play a major role in the development of inflammatory processes, fever and pain.

A decrease in the number of prostaglandins in the center of thermoregulation leads to vasodilation and an increase in sweating, which causes the antipyretic effect of the drug. In addition, the use of acetylsalicylic acid makes it possible to reduce the sensitivity of nerve endings to pain mediators by reducing the effect of prostaglandins on them. When taken orally, the maximum concentration of acetylsalicylic acid in the blood can be observed after 10-20 minutes, and the salicylate formed as a result of metabolism - after 0.3-2 hours. Acetylsalicylic acid is excreted through the kidneys, the half-life is 20 minutes, the half-life for salicylate is 2 hours.

Indications for use of Acetylsalicylic acid

Acetylsalicylic acid, the indications for which are due to its properties, is prescribed for:

• acute rheumatic fever, pericarditis (inflammation of the serous membrane of the heart), rheumatoid arthritis (damage to connective tissue and small vessels), rheumatic chorea (manifested by involuntary muscle contractions), Dressler's syndrome (combination of pericarditis with pleural inflammation or pneumonia);
• pain syndrome of weak and moderate intensity: migraine, headache, toothache, pain during menstruation, osteoarthritis, neuralgia, pain in joints, muscles;
• diseases of the spine, accompanied by pain syndrome: sciatica, lumbago, osteochondrosis;
• febrile syndrome;
• the need to develop tolerance to anti-inflammatory drugs in patients with the "aspirin triad" (a combination of bronchial asthma, nasal polyps and acetylsalicylic acid intolerance) or "aspirin" asthma;
• prevention of the development of myocardial infarction in ischemic heart disease or in the prevention of relapse;
• the presence of risk factors for painless myocardial ischemia, coronary heart disease, unstable angina pectoris;
• prevention of thromboembolism (blockage of the vessel by a thrombus), valvular mitral heart disease, mitral valve prolapse (dysfunction), atrial fibrillation (loss of atrial muscle fibers of the ability to work synchronously);
• acute thrombophlebitis (inflammation of the vein wall and the formation of a blood clot that closes the lumen in it), pulmonary infarction (clogging of the vessel feeding the lung by a thrombus), recurrent pulmonary embolism.

Instructions for the use of Acetylsalicylic acid

Acetylsalicylic acid tablets are intended for oral administration, it is recommended to take after meals with milk, plain or alkaline mineral water.

The instruction recommends to use acetylsalicylic acid for adults 3-4 times a day, 1-2 tablets (500-1000 mg), while the maximum daily dose is 6 tablets (3 g). The maximum duration of use of acetylsalicylic acid is 14 days.

In order to improve the rheological properties of blood, as well as an inhibitor of platelet adhesion, ½ tablets of acetylsalicylic acid are prescribed per day for several months. With myocardial infarction and for the prevention of secondary myocardial infarction, the instruction for acetylsalicylic acid recommends taking 250 mg per day. Dynamic disorders of cerebral circulation and cerebral thromboembolism suggest taking ½ tablet of acetylsalicylic acid with a gradual dose increase to 2 tablets per day.

Acetylsalicylic acid is prescribed for children in the following single doses: over 2 years old - 100 mg, 3rd year old - 150 mg, four years old - 200 mg, over 5 years old - 250 mg. Children are recommended to take acetylsalicylic acid 3-4 times a day.

Side effects

Acetylsalicylic acid, the use should be discussed with a doctor, can provoke side effects such as:

• vomiting, nausea, anorexia, abdominal pain, diarrhea, liver dysfunction;
• visual disturbances, headache, aseptic meningitis, tinnitus, dizziness;
• anemia, thrombocytopenia;
• lengthening of bleeding time, hemorrhagic syndrome;
• impaired renal function, nephrotic syndrome, acute renal failure;
• bronchospasm, Quincke's edema. skin rash, "aspirin triad";
• Reye's syndrome, increased symptoms of chronic heart failure.

Contraindications to the use of Acetylsalicylic acid

Acetylsalicylic acid is not prescribed for:

• gastrointestinal bleeding;
• erosive and ulcerative lesions of the digestive tract in the acute phase;
• The "aspirin triad";
• reactions to the use of acetylsalicylic acid or other anti-inflammatory drugs in the form of rhinitis, urticaria;
• hemorrhagic diathesis (diseases of the blood system, which are characterized by a tendency to increased bleeding);
• hemophilia (slow blood clotting and increased bleeding);
• hypoprothrombinemia (increased tendency to bleed due to a deficiency of prothrombin in the blood);
• dissecting aortic aneurysm (pathological additional false lumen in the thickness of the aortic wall);
• portal hypertension;
• vitamin K deficiency;
• renal or hepatic impairment;
• deficiency of glucose-6-phosphate dehydrogenase;
• Reye's syndrome (serious damage to the liver and brain in children as a result of treatment of viral infections with aspirin).

Acetylsalicylic acid is contraindicated in children under 15 years of age with acute respiratory infections caused by viral infections, lactating patients, as well as pregnant women in the first and third trimester.

Even if the use of the drug suggests indications, acetylsalicylic acid is not prescribed in case of hypersensitivity to it or other salicylates.

Additional Information

According to the instructions, acetylsalicylic acid cannot be stored in a place where the air temperature can rise above 25 ° C. In a dry place and at room temperature, the drug will be usable for 4 years.