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Aspirin (acetylsalicylic acid)

Aspirin (acetylsalicylic acid) is a salicylate drug used as an analgesic for the relief of mild pain, and as an antipyretic and anti-inflammatory agent. Aspirin is also an antiplatelet agent and inhibits the production ofthromboxane , which normally binds the platelet molecule and creates a patch over the damaged blood vessel walls. Since this patch can also expand and block blood flow, aspirin is also used to prevent heart attacks, stroke and blood clots. Aspirin in low doses is used immediately after a heart attack to reduce the risk of recurrence or death of heart tissue. Aspirin can be an effective tool for the prevention of certain types of cancer, especially cancer of the colon and rectum. The main side effects of aspirin are: gastric ulcer, gastric bleeding and tinnitus (especially when taken in large doses). Aspirin is not recommended for children and adolescents with flu-like symptoms or viral diseases because of the risk of developing Ray's syndrome. Aspirin is part of a group of drugs called non-steroidal anti-inflammatory drugs (NSAIDs), but it has a different mechanism of action than most other NSAIDs. Although aspirin and drugs with a similar structure act like other NSAIDs (manifesting antipyretic, anti-inflammatory, analgesic actions) and inhibit the samecyclooxygenase (COX) enzyme , aspirin differs from them in that it acts irreversibly and, unlike other drugs, acts more on COX-1 than on COX-2. The active component of aspirin was first discovered in the willow bark in 1763 by Edward Stone of Wadham College, Oxford. The doctor discovered salicylic acid, an active metabolite of aspirin. Aspirin was first synthesized by Felix Hoffman , a chemist from the German company Bayer , in 1897. Aspirin is one of the most widely used drugs in the world. Annually, around 40,000 tons of aspirin is consumed in the world. In countries where aspirin is a registered trademark of Bayer , generic -acetylsalicylic acid is sold . The drug is on the list of essential medicines of the World Health Organization.

Aspirin for use in medicine

Aspirin is used to treat a range of symptoms, including fever, pain, rheumatic fever, and inflammatory diseases, such as rheumatoid arthritis, pericarditis, and Kawasaki disease. In low doses, aspirin is used to reduce the risk of death due to a heart attack or stroke. There is evidence that aspirin can be used to treat bowel cancer, but the mechanism of its action in this case is not proven.

Aspirin-analgesic

Aspirin is an effective analgesic for the treatment of acute pain, inferior, however, to ibuprofen, because the latter is associated with a lower risk of gastric bleeding. Aspirin is not effective for pain caused by muscle spasms, flatulence, bloating, or severe skin damage. As with other NSAIDs, the efficacy of aspirin increases with admission in combination with caffeine . Effervescent tablets of aspirin, such as Alcoseltser orBlowfish , relieve pain faster than conventional tablets, and are effectively used to treat migraines. Aspirin in the form of an ointment is used to treat certain types of neuropathic pain.

Aspirin and headache

Aspirin, alone or in combination formulas, is effective for the treatment of certain types of headaches. Aspirin may be ineffective for the treatment of secondary headaches (caused by other diseases or injuries).International classification of diseases associated with headaches, stands out among primary headaches tenzionnuyu headache (the most common type of headache), migraine and cluster headaches. For the treatment of a tensile headache, use aspirin or other over-the-counter analgesics. Aspirin, especially as a component of the formula acetaminophen / aspirin / caffeine ( Excedrin Migraine ) is considered to be an effective first-line treatment for migraine, and comparable in effectiveness to low doses of sumatriptan . The drug is most effective for stopping migraine at its beginning.

Aspirin and heat

Aspirin affects not only the pain, but also the heat through the prostaglandin system by irreversible inhibition of COX. Although aspirin is widely approved for use in adults, many medical societies and regulatory agencies (including the American Academy of Family Therapists, the American Academy of Pediatricians and the FDA Food and Drug Administration) do not recommend the use of aspirin as a febrifuge for children.Aspirin may be associated with the risk of developing Ray's syndrome, a rare but often fatal disease associated with the use of aspirin or other salicylates in children in the case of a viral or bacterial infection. In 1986, the FDA ordered manufacturers to place on all labels with aspirin a warning about the risks of using aspirin in children and adolescents.

Aspirin and heart attacks

The first studies of the effects of aspirin on the heart and heart attacks were conducted in the early 1970s by Professor Peter Slate , a distinguished professor of heart medicine from Oxford University, who formed the Aspirin Research Society. In some cases, aspirin can be used to prevent heart attacks. In lower doses, aspirin is effective in preventing the development of existing cardiovascular diseases, as well as in reducing the risk of these diseases in people with a history of such diseases. Aspirin is less effective for people with a low risk of heart attack, for example, for people who have never experienced such a condition in the past.Some studies recommend the use of aspirin on an ongoing basis, while in others, such use is not recommended due to side effects such as gastric bleeding, which usually outweigh any potential benefit of the drug.When using aspirin for preventive purposes, there may be a phenomenon of resistance to aspirin, manifested in a decrease in the effectiveness of the drug, which may lead to an increased risk of heart attack. Some authors suggest testing resistance to aspirin or other antithrombotic drugs before starting treatment . Aspirin has also been proposed as a component of the drug for the treatment of cardiovascular diseases.

Aspirin Post-Surgical Treatment

The US Agency for Health Research and Quality Recommendations recommends the long-term use of aspirin after the procedure of percutaneous coronary intervention, for example, the installation of a stent of thecoronary artery. Often, aspirin is combined with inhibitors of adenosine diphosphate receptors , such as clopidogrel , prasugrel or ticagreolol , to prevent blood clots (double antiplatelet therapy). The recommendations for the use of aspirin in the United States and Europe are somewhat different as to how long and what indications should be given to such combination therapy after surgery. In the United States, double antiplatelet therapy is recommended for a minimum of 12 months, and in Europe 6-12 months after the use of a stent containing medications. However, the recommendations in both countries are consistent in the issue of perpetual use of aspirin after the completion of the course of antiplatelet therapy.

Aspirin and cancer prevention

The effect of aspirin on cancer, especially on intestinal cancer, has been extensively studied. Numerous meta-analyzes and reviews indicate that the continued use of aspirin reduces the long-term risk of bowel cancer and mortality. However, the relationship between the dose of aspirin, the duration of use and various risk factors, including mortality, progression of the disease and the risk of developing the disease, was not revealed. Although much of the data on aspirin and the risk of colon cancer comes from observational studies, rather than from randomized controlled trials, available randomized trial data show that the long-term use of low-dose aspirin can be effective in preventing certain types of colon cancer. In 2007, the US Preventative Service issued a directive on this issue, giving the use of aspirin to prevent bowel cancer with a "D" rating. The service also does not recommend that doctors use aspirin for this purpose.

Other uses of aspirin

Aspirin is used as first-line therapy for symptoms of heat and joint pain in acute rheumatic fever. Treatment often lasts for one to two weeks, and the drug is rarely prescribed for long periods of time. After getting rid of heat and pain, the need for taking aspirin disappears, but the drug does not reduce the risk of heart complications and residual rheumatic heart disease. Naproxen has equal aspirin efficacy and is less toxic, however, due to limited clinical data, naproxen is recommended only as a second-line treatment. For children, aspirin is recommended only with Kawasaki disease and rheumatic fever, due to the lack of high-quality data on its effectiveness. In low doses, aspirin shows an average effectiveness in preventing pre-eclampsia .

Aspirin - Resistance

In some people, aspirin does not work as effectively on platelets as in others. This effect was called " aspirin resistance", or insensitivity. In one study, it was shown that women are more prone to resistance than men.An aggregation study involving 2930 patients showed that 28% of patients develop aspirin resistance. A study of 100 Italian patients showed that, on the other hand, out of 31% of patients resistant to aspirin, only 5% had real resistance, and the rest had incompetence (non-compliance with drug intake standards). Another study involving 400 healthy volunteers showed that none of the patients showed any real resistance, but some observed " pseudo-regressivity , reflecting deferred or reduced absorption of the drug."

Dosage of aspirin

Aspirin tablets for adults are manufactured in standard dosages, which differ slightly in different countries, for example, 300 mg in Britain and 325 mg in the United States. Reduced dosages are also associated with existing standards, for example, 75 mg and 81 mg. Tablets of 81 mg are conventionally called the "infant dose", although they are not recommended for use in children. The difference between 75 and 81 mg tablets does not have a significant medical value. Interestingly, in the US, 325 mg tablets are equivalent to 5 aspirin beads, used up to the metric system used today. In general, for the treatment of fever or arthritis, adults are recommended to take aspirin 4 times a day. For the treatment of rheumatic fever, doses close to the maximum are historically used. For the prevention of rheumatoid arthritis in persons with an existing or suspected coronary artery disease, it is recommended that lower doses be taken once a day. The US Preventative Service recommends the use of aspirin for the primary prevention of coronary heart disease in men aged 45-79 years and women aged 55-79 years only if the potential positive effects (reduction in the risk of myocardial infarction in men or stroke in women) exceed the potential risk gastric damage. A study of the Women's Health Initiative has shown that regular intake of low-dose aspirin (75 or 81 mg) in women reduces the risk of death due to cardiovascular disease by 25% and 14% - the risk of death due to other causes.The use of low-dose aspirin is also associated with a reduction in the risk of cardiovascular disease, and doses of 75 or 81 mg / day can optimize efficacy and safety for patients taking aspirin for long-term prevention.In children with Kawasaki disease, the dose of aspirin is based on body mass data. The drug is taken four times a day for a maximum of four weeks, and then, during the next 6-8 weeks, taken at a lower dose once a day.

Aspirin Side effects

Contraindications

Aspirin is not recommended for persons with an allergy to ibuprofen or naproxen or to persons with intolerance to salicylate, or a more generalized intolerance to NSAIDs. Caution should be observed for people suffering from asthma or bronchospasm caused by the intake of NSAIDs. Since aspirin acts on the walls of the stomach, manufacturers recommend patients suffering from gastric ulcers, diabetes or gastritis, consult a doctor before using aspirin. Even in the absence of the above conditions, with the joint administration of aspirin with warfarin or alcohol increases the risk of gastric bleeding. Patients with hemophilia or other bleeding disorders are not recommended taking aspirin or other salicylates. Aspirin can cause hemolytic anemia in people with a genetic disease deficiency of glucose-6-phosphate dehydrogenase , especially in high doses and depending on the severity of the disease. The use of aspirin in dengue fever is not recommended because of the increased risk of bleeding. Aspirin is also not recommended for persons suffering from kidney disease, hyperuricemia or gout, since aspirin inhibits the ability of the kidneys to excrete uric acid, and thus can exacerbate these diseases. Aspirin is not recommended for children and adolescents to treat the symptoms of flu and cold, because such use may be associated with the development of Ray's syndrome.

Gastrointestinal tract

It has been shown that aspirin increases the risk of gastric bleeding. Even despite the presence of tablets of aspirin with enteric coating positioned as "soft for the stomach," one study showed that even this does not help reduce the harmful effects of aspirin on the stomach. When combined with other NSAIDs, aspirin also increases the risk. When using aspirin in combination with clopidogrel or warfarin the risk of gastric bleeding also increases. Blockade with aspirin COX-1 causes a protective reaction in the form of an increase in COX-2. The use of inhibitors of COX-2 and aspirin leads to increased erosion of the gastric mucosa.Therefore, caution should be exercised when combining aspirin with any natural COX-2 inhibiting additives such as garlic extracts, curcumin , blueberries, pine bark, ginkgo, cod liver oil, resveratrol , genistein ,quercetin , resorcinol and others. To reduce the harmful effects of aspirin on the stomach, in addition to the use of enteric coatings, manufacturing companies use a "buffer" method. "Buffer" substances serve to prevent the accumulation of aspirin on the walls of the stomach, but the effectiveness of such drugs is disputed. As "buffers" are used almost any means used in antacids. In the preparation Bufferin , for example,MgO is used . In other preparations, CaCO3 is used. Not so long ago, to protect the stomach with the intake of aspirin, vitamin C was added to it. When combined, a decrease in the amount of damage is observed, compared with the use of aspirin alone.

The central effect of aspirin

In experiments on rats it was shown that large doses of salicylate, a metabolite of aspirin, cause a temporary ringing in the ears. This occurs as a result of exposure to arachidonic acid and a cascade of NMDA receptors.

Aspirin and Reye's syndrome

Reye's syndrome, a rare but very dangerous disease, is characterized by acute encephalopathy and fatty liver infiltration, and develops with aspirin in children and adolescents in order to lower temperature or to treat other symptoms. From 1981 to 1997, 1207 cases of development of Ray's syndrome among patients under the age of 18 were recorded in the United States. In 93% of cases, patients experienced poor health three weeks before the development of Ray's syndrome, and most often complained of respiratory infections, chicken pox or diarrhea. In the body, salicylates were found in 81.9% of the children. After the association between Ray's syndrome and the intake of aspirin was proven and safety measures were taken (including the treatment of the chief health officer and changes in the packages), aspirin intake in children in the United States dropped sharply, which led to a reduction in the incidence of Ray's syndrome; a similar situation was observed in the UK. FDA USA does not recommend taking aspirin or aspirin containing products for children under 12 years old in the presence of symptoms of heat. The UK Regulatory Agency for Medicines and Medicines does not recommend taking aspirin to children under 16 without a doctor's appointment.

Allergic reactions to aspirin

In some people, aspirin can cause symptoms resembling allergies, including redness and swelling of the skin and headache. This reaction is caused by intolerance to salicylate and is not an allergy in the literal sense of the word, but rather an inability to metabolize even a small amount of aspirin, which can quickly lead to an overdose.

Other side effects of aspirin

In some people, aspirin can cause angioedema (swelling of the skin tissue). In one study, it was shown that in some patients angioedema develops 1-6 hours after taking aspirin. However, angioedema developed only when taking aspirin in combination with other NSAIDs. Aspirin causes an increased risk of cerebral microcirculation, which is shown on MRI as dark spots 5-10 mm in diameter or smaller. These bleedings may be the first signs of ischemic stroke or hemorrhagic stroke, Binswanger 's disease and Alzheimer's disease. A study of a group of patients taking an average dose of aspirin 270 mg per day showed an average absolute increase in the risk of hemorrhagic stroke, equal to 12 cases among 10,000 people. In comparison, the absolute reduction in the risk of myocardial infarction was equal to 137 cases among 10,000 people, and a reduction in the risk of ischemic stroke - to 39 cases among 10,000 people. In the case of an existing hemorrhagic stroke, the use of aspirin increases the risk of death, with doses of about 250 mg per day causing a reduction in the risk of mortality within three months after a hemorrhagic stroke. Aspirin and other NSAIDs can cause hyperkalemia by inhibiting prostaglandin synthesis; However, these drugs are not likely to cause hyperkalemia provided normal hepatic functioning. Aspirin may increase postoperative bleeding for up to 10 days. In one study, it was shown that 30 patients of elective surgery from 6499 because of bleeding required repeated operations. Twenty patients had diffuse bleeding, and 10 had local bleeding. In 19 of 20 patients, diffuse bleeding was associated with preoperative use of aspirin alone or in combination with other NSAIDs.

Aspirin - Overdose

An overdose of aspirin can be acute or chronic. Acute overdose is associated with a single dose of a large dose of aspirin. Chronic overdose is associated with a prolonged intake of doses above the recommended rate. Acute overdose is associated with a 2% risk of death. Chronic overdose is more dangerous and more often has a lethal outcome (in 25% of cases); chronic overdose is especially dangerous in children. When poisoning, various means are used, including activated carbon, sodium dicarbonate , intravenous dextrose and salt and dialysis. To make a diagnosis of poisoning use measurements of salicylate, an active metabolite of aspirin, in plasma, using automated spectrophotometry . The levels of salicylate in plasma with the usual dose are 30-100 mg / l, 50-300 mg / l with high doses and 700-1400 mg / l for acute overdose. Salicylate is also produced by the use of bismuth subsalicylate , methyl salicylate and sodium salicylate.

Interactions of aspirin with other drugs

Aspirin can interact with other drugs. For example, azetazolamide and ammonium chloride increase the harmful effects of salicylates, alcohol also increases gastric bleeding with aspirin. Aspirin can displace some drugs from protein binding sites, including antidiabetic drugs tolbutamyl and chlorpropamide , warfarin , methotrexate , phenytoin , probenecid , valproic acid (by interfering with beta-oxidation, an important part ofvalproate metabolism ), and other NSAIDs. Corticosteroids can also reduce aspirin concentrations. Ibuprofen may reduce antiplatelet effect of aspirin, used to protect the heart and prevent stroke. Aspirin may reduce the pharmacological activity of spironolactone . Aspirin competes with piccilin G for renal tubular secretion. Aspirin can also inhibit the absorption of vitamin C.

Aspirin - Chemical characteristics

Aspirin is rapidly cleaved in solutions of ammonium acetate or acetates, carbonates, citrates or alkali metal hydroxides. It is stable in dry form, but undergoes significant hydrolysis upon contact with acetyl or salicylic acid. In the reaction with alkali, hydrolysis quickly occurs, and the pure solutions formed can consist entirely of acetate or salicylate.

Physical characteristics of aspirin

Aspirin, an acetyl derivative of salicylic acid, is a white, crystalline, slightly acidic compound with a melting point of 136 ° C (277 ° F) and a boiling point of 140 ° C (284 ° F). The acid dissociation constant of the substance ( pKa ) is 25 ° C (77 ° F).

Synthesis of aspirin

Synthesis of aspirin is classified as an esterification reaction . Salicylic acid is treated with acetyl anhydride, an acid derivative, causing a chemical reaction that converts the hydroxy group of salicylic acid to an ester group (R-OH → R-OCOCH3). As a result, aspirin and acetyl acid are formed, which is considered a by-product of this reaction. Small amounts of sulfuric acid (and sometimes phosphoric acid) are usually used as catalysts .

Aspirin - The mechanism of action

The discovery of the mechanism of action of aspirin In 1971, the British pharmacologist John Robert Wayne , who was later admitted to the Royal College of Surgery in London, demonstrated that aspirin inhibits the production of prostaglandins and thromboxanes . For this discovery, the scientist was awarded the Nobel Prize in Medicine in 1982, in conjunction with Sune Bergström and Bengt Samuelson . In 1984 he was awarded the title of a knight-bachelor.

Suppression of prostaglandins and thromboxanes

The ability of aspirin to inhibit the production of prostaglandins and thromboxanes is associated with its irreversible inactivation of the enzyme cyclooxygenase (COX, officially called prostaglandin- endoperoxide synthase ) associated with the synthesis of prostaglandin and thromboxane . Aspirin acts as an acetylating agent, with the covalent attachment of the acetyl group to the serine residue on the active site of the COX enzyme. This is the main difference between aspirin and other NSAIDs (such as diclofenac and ibuprofen), which are reversible inhibitors. Aspirin in low doses irreversibly blocks the formation of thromboxane A2 in platelets, having an inhibitory effect on platelet aggregation during their life cycle (8-9 days). Due to this antithrombotic effect, aspirin is used to reduce the risk of heart attack. Aspirin at a dose of 40 mg per day can inhibit a large percentage of the maximum release of thromboxane A2, with little effect on the synthesis of prostaglandin I2; however, high doses of aspirin may increase inhibition. Prostaglandins, local hormones produced in the body, show different effects, including affect the transmission of pain signals to the brain, modulation of the hypothalamic thermostat and inflammation. Thromboxanes are responsible for the aggregation of platelets, which form blood clots. The main cause of a heart attack is a thickening of the blood, and low-dose aspirin is recognized as an effective means of preventing acute myocardial infarction. An undesirable side effect of the antithrombotic effect of aspirin is that it can provoke excessive bleeding.

Inhibition of COX-1 and COX-2

There are at least two types of cyclooxygenase : COX-1 and COX-2. Aspirin irreversibly inhibits COX-1 and modifies the enzymatic activity of COX-2. COX-2 usually produces prostanoids , most of which are pro-inflammatory . Aspirin-modified PTGS2 produces lipoxins , most of which are anti-inflammatory. To inhibit only PTGS2 and reduce the risk of gastrointestinal side effects, new generation NSAIDs, COX-2 inhibitors, have been developed. However, not so long ago, new-generation COX-2 inhibitors, such as rofecoxib ( Vioxx ) were withdrawn from the market, after the data that PTGS2 inhibitors increase the risk of a heart attack. Endothelial cells express PTGS2, and, by selective inhibition of PTGS2, reduce the production of prostaglandin (namely, PGI2; prostacyclin ), depending on the levels of thromboxane . Thus, the protective anticoagulant effect of PGI2 decreases and the risk of blood clots and heart attacks increases. Because platelets do not have DNA, they can not synthesize the new PTGS. Aspirin irreversibly inhibits the enzyme, which is the most important difference from reversible inhibitors.

Additional mechanisms of action of aspirin

Aspirin has at least three additional mechanisms of action. It blocks oxidative phosphorylation in the cartilaginous (and renal) mitochondria, by diffusion from the inner membrane region as a proton carrier back to the mitochondrial space where it is again ionized to release protons. In short, aspirin buffers and carries protons. When taken in large doses, aspirin can cause fever, due to a temperature release from the electron transport chain. In addition, aspirin promotes the formation of NO-radicals in the body, which, as shown in experiments on mice, is an independent mechanism to reduce inflammation. Aspirin reduces the adhesion of leukocytes, which is an important mechanism of immune defense against infections; however, these data are not conclusive evidence of the effectiveness of aspirin against infections. More recent data also show that salicylic acid and its derivatives modulate signaling via NF- κB . NF- κB , the transcription factor complex, plays an important role in many biological processes, including inflammation. In the body, aspirin breaks down quickly to salicylic acid, which itself has anti-inflammatory, anti -temperature and analgesic effects. In 2012, it was shown that salicylic acid activates AMP-activated protein kinase , which may be a possible explanation for some of the effects of salicylic acid and aspirin. Acetyl in the molecule of aspirin also has a special effect on the body. Acetylation of cellular proteins is an important phenomenon affecting the regulation of protein function at the post-translational level. Recent research shows that aspirin can acetylate not only COX isoenzymes. These acetylation reactions can explain many of the unexplained effects of aspirin to date.

Hypothalamic- hypophyseal-adrenal activity

Aspirin, like other drugs that affect prostaglandin synthesis, has a powerful effect on the pituitary gland, and indirectly affects some hormones and physiological functions. The effects of aspirin on growth hormone, prolactin and thyroid stimulating hormone (with relative effects on T3 and T4) were directly proven. Aspirin reduces the effect of vasopressin and increases the effect of naloxone by secretion of adrenocorticotropic hormone and cortisol in the hypothalamic- adipophasal-adrenal axis, which occurs by interaction with endogenous prostaglandins.

Aspirin - Pharmacokinetics

Salicylic acid is a weak acid and a very small part of it is ionized in the stomach after oral administration. Acetylsalicylic acid is slightly soluble in the acidic environment of the stomach, so that its absorption can be delayed for 8-24 hours when taken in high doses. Increased pH and a large area of the small intestine contribute to the rapid absorption of aspirin in this area, which in turn contributes to a greater dissolution of salicylate. However, in case of an overdose, aspirin dissolves much more slowly, and its plasma concentrations may increase within 24 hours after administration. About 50-80% of salicylate in the blood binds to protein albumin , and the remainder remains in the active ionized form; the binding of proteins depends on the concentration. Saturation of binding sites leads to an increase in the amount of free salicylate and an increase in toxicity. The volume of distribution is 0.1-0.2 l / kg. Acidosis increases the volume of distribution due to increased cellular penetration of salicylates. 80% of the therapeutic dose of salicylic acid is metabolized in the liver. When bound to glycine , salicylicuric acid is formed , and with glucuronic acid, salicylic acid and phenolic glucoronide are formed . These metabolic pathways have only limited capacity. A small amount of salicylic acid also hydrolyzes in gentisic acid. When taking large doses of salicylate, the kinetics shifts from the first to the zero order, as the metabolic pathways become saturated and the importance of renal excretion increases. Salicylates are secreted from the body with kidneys in the form of salicylic acid (75%), free salicylic acid (10%), salicylic phenol (10%) and acyl glucuronides (5%), gentisic acid (<1 %) and 2,3- dihydroxybenzoic acid. When taking small doses (less than 250 mg in adults), all paths undergo first-order kinetics, with a half-life of 2.0 to 4.5 hours. When taking large doses of salicylate (more than 4 g), the half-life increases (15-30 hours), since biotransformation includes forming salitsilurovoy acid and saturation salicyl phenolic glucuronide . With an increase in urine pH from 5 to 8, there is an increase in renal clearance by a factor of 10-20.

Aspirin - History of discovery

Herbal extracts, including Willow and Willow bark (spiraea), the active ingredient of which is salicylic acid, have been used since ancient times to relieve headaches, pain and heat. The father of modern medicine Hippocrates (460 - 377 BC) described the use of powder from the bark and leaves of the willow to alleviate such symptoms. The French chemist Charles Frederick Gerhard first produced acetylsalicylic acid in 1853. While working on the synthesis and properties of various acid anhydrides, he mixed acetyl chloride with a sodium salt of salicylic acid (sodium salicylate). A powerful reaction followed, and the resultant alloy wasmodified . Gerhard called this compound " salicylic-acetyl anhydride" ( wasserfreie Salicylsäure-Essigsäure ). Six years later, in 1859, von Gilm received analytically pure acetylsalicylic acid (which he called acetylierte Salicylsäure , acetylated salicylic acid) during the reaction of salicylic acid and acetyl chloride. In 1869 Schroeder , Prince and Kraut repeated the experiments of Gerhard and von Guilma and reported that both reactions lead to the synthesis of the same substance - acetylsalicylic acid. They first described the correct structure of the substance (in which the acetyl group is attached to phenolic oxygen). In 1897, chemists from Bayer AG produced a synthetically altered version of salicin, extracted from the plant Filipendula ulmaria (tavolga), which causes less irritation to the stomach, compared to pure salicylic acid. It is still not clear who was the chief chemist who conceived this project. Bayer reported that the work was carried out by Felix Hoffmann , but the Jewish chemist Arthur Eichengrun stated later that he was the chief developer and records of his contribution were destroyed during the Nazi regime. A new drug, formally acetylsalicylic acid, was called Bayer AG " Aspirin ", according to the old botanical name of the plant in which it is contained (tavolga), Spiraea ulmaria . The word " Aspirin " is derived from the words " acetyl " and " Spirsäure ", the old German word for salicylic acid, which in turn comes from the Latin " Spiraea ulmaria ". By 1899Bayer already engaged in the sale of aspirin all over the world. The popularity of aspirin increased in the first half of the 20th century, due to its perceived effectiveness in the treatment of the epidemic of the Spanish flu of 1918. Recent studies, however, show that the general mortality from influenza in 1918 was partly caused by aspirin, but this statement is controversial and is not widely recognized in academia. The popularity of aspirin led to the emergence of fierce competition and the separation of brands of aspirin, especially after the expiration of the US patent Bayer in 1917. After the advent of paracetamol ( acetaminophen ) in 1956 and ibuprofen in 1969, the popularity of aspirin somewhat decreased. In the 1960s and 1970s John Wayne and his team discovered the main mechanisms of action of aspirin, and clinical trials and other studies conducted between the 1960s and 1980s. demonstrated that aspirin is an effective anti-clotting drug. In the last decades of the 20th century, aspirin sales rose again, and remain at a fairly high level to this day.

Trade mark of aspirin

In the framework of the Treaty of Versailles reparations of 1919, after the defeat of Germany in the First World War, aspirin (and also heroin) lost the status of a registered trademark in France, Russia, the United Kingdom and the United States, where they became generics . To date, aspirin is considered a generic in Australia, France, India, Ireland, New Zealand, Pakistan, Jamaica, Colombia, the Philippines, South Africa, the United Kingdom and the United States. Aspirin, with the capital "A", remains a registered trademark of Bayer in Germany, Canada, Mexico and more than 80 other countries where the trademark is the property of Bayer .

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Alexandra 17:27 | 02/13/2018 Many thanks to you for your valuable, practically, exhaustive publications about medicines! Success to you in everything! Health!