Aspirin , also known as acetylsalicylic acid ( ASA ), is a drug used to treat pain, fever, or inflammation. Specific inflammatory conditions in which aspirin is used include Kawasaki disease, pericarditis, and rheumatic fever. Aspirin given immediately after a heart attack lowers the risk of death. Aspirin is also used long-term to help prevent heart attacks, ischemic stroke, and blood clots in people at high risk. It can also reduce the risk of certain types of cancer, especially colorectal cancer. For pain or fever, effects usually begin within 30 minutes. Aspirin is a nonsteroidal anti-inflammatory drug (NSAID) and works similarly to other NSAIDs but also suppresses the normal function of platelets.
One of the common side effects is abdominal pain. More significant side effects include stomach ulcers, abdominal bleeding, and worsening asthma. The risk of bleeding is greater among those who are older, drinking alcohol, taking other NSAIDs, or being in other blood thinners. Aspirin is not recommended in the later part of pregnancy. It is generally not recommended in children with infections because of the risk of Reye's syndrome. High doses can cause ringing ears.
Aspirin precursors in the form of leaves from willow trees have been used for its health effects for at least 2,400 years. In 1853, the chemist, Charles FrÃÆ'Â © ÃÆ'¨ ric Gerhardt, treated the drug sodium salicylate with acetyl chloride to produce acetylsalicylic acid for the first time. Over the next fifty years, other chemists established chemical structures and produced more efficient methods to make them. In 1897, scientists at the Bayer company began studying acetylsalicylic acid as a replacement drug that did not irritate common salicylate medicines. In 1899, Bayer named it "Aspirin" and sold it all over the world. The popularity of Aspirin grew in the first half of the 20th century which led to competition between many brands and formulations. The word Aspirin is a Bayer brand name; however, their rights to trademarks are lost or sold in many countries.
Aspirin is one of the most widely used drugs globally, with an estimated 40,000 tons (44,000 tons) (50 to 120 billion pills) consumed each year. This is the WHO Essential Drug List (WHO), the safest and most effective medication needed in the health system. In 2014, wholesale costs in developing countries are $ 0.002 to $ 0.025 USD per dose. By 2015, the cost for one month of treatment in the United States is less than $ 25.00 USD. It is available as a generic drug.
Video Aspirin
Medical use
Aspirin is used in the treatment of a number of conditions, including fever, pain, rheumatic fever, and inflammatory diseases, such as rheumatoid arthritis, pericarditis, and Kawasaki's disease. Lower doses of aspirin have also been shown to reduce the risk of death from heart attacks, or the risk of stroke in some circumstances. There is some evidence that aspirin effectively prevents colorectal cancer, although the mechanism of this effect is unclear. In the United States low-dose aspirin is considered fair in those between the ages of 50 and 70 who have more than 10% of the risk of cardiovascular disease and do not experience an increased risk of healthy bleeding.
Pain
Aspirin is an effective analgesic for acute pain, but is generally thought to be lower than ibuprofen for pain relief because aspirin is more likely to cause gastrointestinal bleeding. Aspirin is generally ineffective for pain caused by muscle cramps, bloating, gastric distension, or acute skin irritation. Like other NSAIDs, the combination of aspirin and caffeine provides more pain relief than aspirin alone. Aspirin effervescent formulations, such as Alka-Seltzer or Blowfish, relieve pain faster than aspirin in tablets, which makes them useful for migraine treatment. Topical aspirin may be effective for treating some types of neuropathic pain.
Headache
Aspirin, either by itself or in a joint formulation, effectively treats some types of headaches, but its efficacy can be questioned for others. Secondary headaches, which means that caused by other disorders or trauma, should be treated promptly by the medical provider.
Among the primary headaches, International Headache Disorder Classification distinguishes between tension headaches (most common), migraines, and cluster headaches. Other aspirin or over-the-counter analgesics are widely recognized to be effective for the treatment of tension headaches.
Aspirin, especially as a combination component of aspirin/paracetamol/caffeine, is considered first-line therapy in the treatment of migraine, and is proportional to the low dose of sumatriptan. It is very effective to stop migraines when they first start.
Fever
Like its ability to control pain, the ability of aspirin to control fever is due to its action on the prostaglandin system through irreversible COX inhibition. Although the use of aspirin as an antipyretic in adults is well established, many medical societies and regulatory bodies (including the American Academy of Family Physicians, the American Academy of Pediatrics, and the US Food and Drug Administration (FDA)) strongly advise against using aspirin for the treatment of fever in children because of the risk of Reye's syndrome, a rare but often fatal disease associated with the use of aspirin or other salicylates in children during episodes of viral or bacterial infection. Because of the risk of Reye syndrome in children, in 1986, the FDA required labeling of all aspirin-containing drugs advising its use in children and adolescents.
Inflammation
Aspirin is used as an anti-inflammatory agent for acute and long-term inflammation, as well as for the treatment of inflammatory diseases, such as rheumatoid arthritis.
Heart attack and stroke
Aspirin is an important part of treatment for those with myocardial infarction (heart attack). One trial found that among those likely to have an elevated ST-segment MI, aspirin saved lives 1 in 42 by reducing the 30-day mortality rate from 11.8% to 9.4%. There was no difference in major bleeding, but there was a small increase in mild bleeding of about 1 in every 167 people given aspirin.
High risk
For people who have had a heart attack or stroke, taking aspirin every day for two years prevents 1 in 50 of cardiovascular problems (heart attack, stroke, or death), but also causes non-fatal bleeding problems to occur in 1 in 400 people.
Lower risk
In those who did not have a previous history of heart disease, aspirin reduces the risk of nonfatal myocardial infarction but does not alter the risk of death as a whole. One study found that among those who had never had a heart attack or stroke, taking aspirin daily for 1 year prevented 1 in 1667 from a heart attack or non-fatal stroke, but caused 1 in 3,333 to have non-fatal bleeding events.. However, the study population had a relatively higher risk than those who had never had a heart attack or stroke.
Aspirin seems to offer little benefit to those at lower risk of heart attack or stroke - for example, those who have no history of this incident or with pre-existing diseases. Some studies recommend aspirin on a case-by-case basis, while others suggest the risk of other events, such as gastrointestinal bleeding, enough to exceed potential benefits, and recommended not to use aspirin for full primary prevention. Aspirin has also been suggested as a component of polypill for the prevention of cardiovascular disease.
Complications of aspirin use for prevention are aspirin-resistance phenomena. For people who are resistant, the efficacy of aspirin is reduced. Some authors suggest a testing regimen to identify people who are resistant to aspirin.
After operation
After percutaneous coronary intervention (PCIs), such as coronary artery stenting, the Health Research Agency and the US Quality Guidelines recommend that aspirin be drunk indefinitely. Often, aspirin is combined with an ADP receptor inhibitor, such as clopidogrel, prasugrel, or ticagrelor to prevent blood clots. This is called dual antiplatelet therapy (DAPT). The US and EU guidelines do not agree on how long, and for what indication this combination therapy should be continued after surgery. The US Guidelines recommend DAPT for at least 12 months, while the EU guidelines recommend DAPT for 6-12 months after placement of drug-eluting stents. However, they agree that aspirin will continue indefinitely after DAPT is complete.
Cancer prevention
Aspirin is thought to reduce overall risk for cancer and death from cancer. This effect is particularly beneficial for colorectal cancer (CRC) but should be taken for at least 10-20 years to see this benefit. It can also slightly reduce the risk of endometrial cancer, breast cancer, and prostate cancer.
Some conclude the benefits outweigh the risks due to bleeding in those at average risk. Others are not clear whether the benefits outweigh the risks. Given this uncertainty, the 2007 United Nations Prevention Task guidelines on this topic recommended the use of aspirin for CRC prevention in people at average risk. However, nine years later, the USPSTF issued a B-level recommendation for the use of low-dose aspirin (75 to 100 mg/day) "for primary prevention of CVD [cardiovascular disease] and CRC in adults 50 to 59 years who had a 10% or higher risk 10 years CVD, no high risk of bleeding, have a life expectancy of at least 10 years, and are willing to take low-dose aspirin every day for at least 10 years.
Other uses
Aspirin is the first-line treatment for fever and symptoms of acute rheumatic fever joint pain. Treatment often lasts for one to two weeks, and is rarely indicated for longer periods. Once the fever and pain subside, aspirin is no longer necessary, as it does not decrease the incidence of cardiac complications and remaining rheumatic heart disease. Naproxen has been shown to be as effective as aspirin and less toxic, but because of limited clinical experience, naproxen is recommended only as second-line treatment.
Along with rheumatic fever, Kawasaki's disease remains one of the few indications for aspirin use in children despite the lack of high quality evidence for its effectiveness.
Low-dose aspirin supplements have moderate benefits when used for the prevention of pre-eclampsia. This benefit is greater when it starts early in pregnancy.
Resistance
For some people, aspirin does not have a strong effect on platelets as for others, an effect known as aspirin resistance or insensitivity. One study showed that women were more likely to be resistant than men, and a different aggregate study of 2,930 people found 28% resistance. A study of 100 Italians, though, found, of 31% of aspirin-resistant subjects, only 5% were completely resistant, and the others were disobedient. Another study of 400 healthy volunteers found no truly resistant subjects, but some had "pseudoresistance, reflecting delays and reducing drug absorption".
Dose
Adult aspirin tablets are produced in standard sizes, slightly different from one country to another, for example 300 mg in the UK and 325 mg (or 5 eggs) in the United States. Smaller doses are based on this standard, tablets for example. , 75 mg and 81 mg. The 81 mg tablets (1 1 / 4 -grain) are commonly called "baby aspirin" or "baby-strength", as they were originally - but no longer - is meant to be given to infants and children. No medical significance occurred due to small differences in doses between 75 mg and 81 mg tablets.
In general, for adults, doses are taken four times a day for fever or arthritis, with doses approaching the maximum daily dose used historically for the treatment of rheumatic fever. For the prevention of myocardial infarction (MI) in a person with documented or suspected coronary artery disease, a much lower dose is taken once daily.
The March 2009 recommendation from the USPSTF on the use of aspirin for the primary prevention of coronary heart disease encourages men aged 45-79 and women aged 55-79 to take aspirin when the potential benefits of reducing MI for men or stroke for women exceed the potential danger of increased gastrointestinal bleeding. The WHI study says ordinary low-dose aspirin women (75 or 81 mg) have a 25% lower risk of death from cardiovascular disease and a 14% lower risk of death from any cause. The use of low-dose aspirin is also associated with a low risk of cardiovascular events, and a lower dose of aspirin (75 or 81 mg/day) can optimize the efficacy and safety of people who need aspirin for long-term prevention.
In children with Kawasaki's disease, aspirin is taken at a weight-based dose, initially four times daily for two weeks and then at a lower dose once daily for six to eight weeks.
Maps Aspirin
Adverse effects
Contraindications
Aspirin should not be taken by people allergic to ibuprofen or naproxen, or who have more common salicylate intolerance or drug intolerance to NSAIDs, and caution should be exercised in those with asthma or NSAID-induced bronchospasm. Because of its effect on the stomach lining, manufacturers recommend people with peptic ulcer, mild diabetes, or gastritis seeking medical advice before using aspirin. Even if none of these conditions, the risk of abdominal bleeding is still elevated when aspirin is taken with alcohol or warfarin. People with hemophilia or other bleeding tendencies should not take aspirin or other salicylates. Aspirin is known to cause hemolytic anemia in people who have a genetic disease lacking glucose-6-phosphate dehydrogenase, especially in large doses and depending on the severity of the disease. The use of aspirin during dengue is not recommended because of the increased bleeding tendency. People with kidney disease, hyperuricemia, or uric acid should not take aspirin because it inhibits the kidney's ability to excrete uric acid, which can aggravate the condition. Aspirin should not be given to children or adolescents to control flu or influenza symptoms, as this has been linked to Reye's syndrome.
Gastrointestinal
Aspirin use has been shown to increase the risk of gastrointestinal bleeding. Although some aspirin-coated aspirin formulations are advertised as "soft for the stomach", in one study, the enteric coating does not seem to reduce this risk. Combining aspirin with other NSAIDs has also been shown to increase this risk further. The use of aspirin in combination with clopidogrel or warfarin also increases the risk of upper gastrointestinal bleeding.
The COX-1 blockade by aspirin apparently results in an increase in COX-2 regulation as part of gastric defenses and that taking COX-2 inhibitors along with aspirin increases the erosion of the gastric mucosa. Therefore, caution should be done when combining aspirin with a "natural" supplement with COX-2 inhibitor properties, such as garlic extract, curcumin, bilberry, pine bark, ginkgo, fish oil, resveratrol, genistein, quercetin, resorcinol, and others..
In addition to the enteric layer, "buffering" is another company's method used to try to reduce the problem of gastrointestinal bleeding. Buffering agents are meant to work by preventing aspirin concentrating on the stomach wall, although the benefits of undisputed aspirin are debatable. Almost all of the buffer agents used in antacids may be used; Bufferin, for example, uses magnesium oxide. Other preparations use calcium carbonate.
Consuming vitamin C has been studied as a method to protect the stomach lining. Taking the same dose of vitamin C and aspirin can reduce the amount of stomach damage that occurs compared to taking aspirin alone.
Middle effect
Large doses of salicylate, aspirin metabolite, cause temporary tinnitus (ringing in the ears) based on experiments on mice, through action on arachidonic acid and NMDA cascade receptors.
Reye's Syndrome
Reye's syndrome, a rare but severe disease characterized by acute encephalopathy and fatty liver, can occur when children or adolescents are given aspirin for fever or other illness or infection. From 1981 to 1997, 1207 cases of Reye syndrome in people younger than 18 were reported to the US Centers for Disease Control and Prevention. Of these, 93% reported pain within three weeks before the onset of Reye's syndrome, most commonly with respiratory tract infections, chicken pox, or diarrhea. Salicylates were detected in 81.9% of children whose test results were reported. Once the relationship between Reye's syndrome and aspirin is reported, and safety measures to prevent it (including Surgeon General warnings, and changes to aspirin-containing drug labels) are implemented, aspirin taken by children declines significantly in the United States, reported cases of Reye syndrome; a similar decrease was found in the UK after a warning against the use of pediatric aspirin was excluded. The US Food and Drug Administration is now recommending aspirin (or aspirin-containing products) should not be given to anyone under the age of 12 who has a fever, and the UK National Health Service recommends children under the age of 16 should not take aspirin, unless it's on doctor's advice.
Skin
For a small number of people, taking aspirin can produce symptoms that resemble allergic reactions, including itching, swelling, and headaches. This reaction is caused by salicylate intolerance and not a true allergy, but an inability to metabolize even a small amount of aspirin, resulting in an overdose.
Aspirin and other NSAIDs, such as ibuprofen, can delay the healing of skin lesions. Aspirin can somehow help cure leg ulcers that have not healed after the usual treatment.
Other adverse effects
Aspirin can cause skin tissue swelling in some people. In one study, angioedema appeared one to six hours after ingesting aspirin in some people. However, when aspirin is taken alone, it does not cause angioedema in these people; aspirin has been combined with other drugs induced by NSAIDs when angioedema develops.
Aspirin leads to an increase in cerebral micro risk that has an appearance on MRI scans of 5 to 10 mm or smaller, hypointens spots (dark holes). Such cerebral microbleed is important, as it often occurs before ischemic stroke or intracerebral hemorrhage, Binswanger's disease, and Alzheimer's disease.
A group study with an average dose of aspirin of 270 mg per day predicted an average absolute risk increase in intracerebral hemorrhage (ICH) of 12 events per 10,000 people. In comparison, the estimated absolute risk reduction in myocardial infarction was 137 events per 10,000 people, and a reduction of 39 events per 10,000 people in ischemic stroke. In cases where ICH has occurred, the use of aspirin produces higher mortality, with a dose of about 250 m per day which results in a relative risk of death within three months after ICH is about 2.5 (95% confidence interval 1.3 to 4.6 ).
Aspirin and other NSAIDs can cause abnormally high blood potassium levels by inducing hypoaldosteronic hyporeninemic state by inhibition of prostaglandin synthesis; However, these agents usually do not cause their own hyperkalemia in the regulation of normal kidney function and euvolemic state.
Aspirin can cause prolonged bleeding after surgery for up to 10 days. In one study, 30 of the 6499 people who underwent elective surgery required re-surgery to control the bleeding. Twenty had diffuse bleeding and 10 had bleeding from a site. Diffuse, but not separately, bleeding is associated with the use of preoperative aspirin alone or in combination with other NSAIDs in 19 of the 20 diffuse bleeding.
On July 9, 2015, the FDA tightened warnings of increased heart attacks and stroke risk associated with nonsteroidal anti-inflammatory drugs (NSAIDs). Aspirin is an NSAID but is unaffected by new warnings.
Overdose
Overdose of aspirin can be acute or chronic. In acute poisoning, a large dose is taken; in chronic poisoning, higher than the normal dose taken over a period of time. Acute overdose has a 2% mortality rate. Chronic overdose is more often lethal, with a 25% mortality rate; Chronic overdose can be very severe in children. Toxicity is administered with a number of potential treatments, including activated charcoal, intravenous dextrose and normal saline, sodium bicarbonate, and dialysis. The diagnosis of poisoning usually involves the measurement of plasma salicylates, the active metabolite of aspirin, by the automatic spectrophotometric method. The plasma salicylate levels generally range from 30-100 mg/l after the usual dose of therapy, 50-300 mg/l in people taking high doses and 700-1400 mg/l after an acute overdose. Salicylates are also produced as a result of exposure to bismuth subsalicylate, methyl salicylate, and sodium salicylate.
Interactions
Aspirin is known to interact with other drugs. For example, acetazolamide and ammonium chloride are known to increase the intoxicating effects of salicylates, and alcohol also increases the gastrointestinal bleeding associated with these types of drugs. Aspirin is known to replace a number of drugs from blood protein binding sites, including tobbutamide and chlorpropamide antidiabetic drugs, warfarin, methotrexate, phenytoin, probenecid, valproic acid (as well as disrupting oxidation of beta, an important part of valproate). metabolism), and other NSAIDs. Corticosteroids can also reduce aspirin concentrations. Ibuprofen can negate the antiplatelet effect of aspirin used for cardiovascular protection and stroke prevention. Spironolactone pharmacological activity can be reduced by taking aspirin, and is known to compete with penicillin G for renal tubular secretion. Aspirin can also inhibit the absorption of vitamin C.
Chemical properties
Aspirin decomposes rapidly in a solution of ammonium acetate or acetate, carbonate, citrate, or hydroxide of an alkali metal. It is stable in dry air, but gradually hydrolysis in contact with water vapor for acetic acid and salicylate. In a solution with alkali, the hydrolysis proceeds rapidly and a clear solution is formed which can comprise entirely of acetate and salicylate.
Like flour mills, factories that make aspirin tablets should pay attention to how much powder goes into the air inside the building, because air-blended powders can explode. The National Institute for Occupational Safety and Health (NIOSH) has set the recommended exposure limits in the United States 5 mg/m 3 (time-weighted average). In 1989, the Occupational Safety and Health Administration (OSHA) set a legal allowable exposure limit for aspirin of 5 mg/m 3 , but this was emptied by AFL-CIO v. OSHA decision in 1993.
Synthesis
The synthesis of aspirin is classified as an esterification reaction. Salicylic acid is treated with acetic anhydride, an acid derivative, causing a chemical reaction that converts a salicylic acid hydroxyl group into an ester group (R-OH -> R-OCOCH 3 ). This process produces aspirin and acetic acid, which is considered a by-product of this reaction. A small amount of sulfuric acid (and sometimes phosphoric acid) is almost always used as a catalyst. This method is usually used in undergraduate teaching laboratories.
- Reaction mechanism
Formulations containing high concentrations of aspirin often smell like vinegar because aspirin can decompose through hydrolysis in humid conditions, producing salicylic acid and acetic acid.
Physical properties
Aspirin, an acetyl derivative of salicylic acid, is white, crystalline, weakly acidic, with a melting point of 136 Ã, Â ° C (277 Ã, Â ° F), and a boiling point of 140 Ã, Â ° C (284 Ã, Â ° F). The dissociation constant of the acid (p K a ) is 3.5 at 25 Ã, Â ° C (77Ã, Â ° F).
Polymorphism
Polymorphism, or the ability of a substance to form more than one crystal structure, is important in the development of pharmaceutical ingredients. Many drugs receive regulatory approval for either single or polymorphic crystals. For a long time, only one crystal structure for aspirin was known. The aspirin may have a second suspected crystal form since the 1960s. The second elusive polymorph was first discovered by Vishweshwar and colleagues in 2005, and details of fine structure were given by Bond et al. New types of crystals were found after experiments of crystallization of aspirin and levetiracetam from hot acetonitrile. The form II is only stable at 100 K and returns to form I at room temperature. In the unambiguous form I, two molecules of salicylate form a centrosymmetric dimer through an acetyl group with a methyl proton (acid) for the carbonyl hydrogen bond, and in the newly claimed form II, each molecule of salicylate forms the same hydrogen bond with two adjacent molecules. instead of one. With respect to hydrogen bonds formed by carboxylic acid groups, both polymorphs form identical dimeric structures.
Action mechanism
Discovery mechanism
In 1971, the English pharmacist John Robert Vane, employed by the Royal College of Surgeons in London, showed aspirin suppressed the production of prostaglandins and thromboxanes. For this discovery he was awarded the 1982 Nobel Prize in Physiology or Medicine, together with Sune BergstrÃÆ'¶m and Bengt Ingemar Samuelsson.
Prostaglandin and thromboxanes
Aspirin's ability to suppress the production of prostaglandins and thromboxanes is due to the irreversible inactivation of cyclooxygenase enzymes (COX, officially known as prostaglandin-endoperoxide synthase, PTGS) necessary for prostaglandin and thromboxane synthesis. Aspirin acts as an acetylating agent in which the acetyl group is covalently attached to the serine residue at the active site of the PTGS enzyme (Inhibition of suicide). This makes aspirin different from other NSAIDs (such as diclofenac and ibuprofen), which are reversible inhibitors.
Irreversible use of low irreversible aspirin blocks the formation of thromboxane A 2 on platelets, resulting in an inhibitory effect on platelet aggregation over the life span of affected platelets (8-9 days). These antiprombotic properties make aspirin useful for reducing the incidence of heart attacks in people who have heart attacks, unstable angina, ischemic stroke or transient ischemic attacks. 40 mg of aspirin a day was able to inhibit most of the acute provoked A 2 acute thromboxane, with slightly affected prostaglandin I2 synthesis; however, a higher aspirin dose is required to achieve further inhibition.
Prostaglandins, locally produced hormones, have various effects, including the transmission of pain information to the brain, modulation of the hypothalamus thermostat, and inflammation. Thromboxanes are responsible for the aggregation of platelets that make up blood clots. Heart attacks are primarily caused by blood clots, and low doses of aspirin are seen as effective medical interventions for acute myocardial infarction.
COX-1 and COX-2 inhibition
At least two different types of cyclooxygenase, COX-1 and COX-2, are acted upon by aspirin. Aspirin inhibits COX-1 irreversibly and modifies COX-2 enzymatic activity. COX-2 usually produces prostanoid, mostly proinflammatory. Aspirin-modified PTGS2 produces lipoxin, largely anti-inflammatory. Newer NSAID drugs, COX-2 inhibitors (coxibs), have been developed to inhibit only PTGS2, with a view to reducing the incidence of gastrointestinal side-effects.
However, several new COX-2 inhibitors, such as rofecoxib (Vioxx), have been withdrawn in the last decade, after evidence emerged that PTGS2 inhibitors increased the risk of heart attack and stroke. Endothelial cells lining the microvasculature in the body are proposed to express PTGS2, and, with selectively inhibiting PTGS2, prostaglandin production (in particular, PGI2; prostacycline) is downregulated with respect to thromboxane levels, because PTGS1 in platelets is unaffected. Thus, the protective anticoagulative effects of PGI2 are removed, increasing the risk of thrombus and associated heart attacks and other circulatory problems. Because platelets do not have DNA, they can not synthesize new PTGS after aspirin irreversibly inhibits the enzyme, an important difference with reversible inhibitors.
Furthermore, aspirin, while inhibiting COX-2's ability to form pro-inflammatory products such as prostaglandins, alters the activity of these enzymes from cyclooxygenases that form prostaglandins into lipoxygenase-like enzymes: the aspirin-treated COX-2 metabolizes various polyunsaturated fatty acids for hydroperoxy products. then further metabolized into specialized mediators who are proresolving such as aspirin-induced aspacin, aspirin-triggered resolvins, and aspirin-induced maresin. This mediator has a strong anti-inflammatory activity. It is proposed that this triggers the transition of aspirin from COX-2 from cyclooxygenase to lipoxygenase activity and the formation of special proresolving mediator formers contributes to the anti-inflammatory effects of aspirin.
Additional mechanisms
Aspirin has been shown to have at least three additional action modes. This separates the oxidative phosphorylation of the cartilaginat (and hepatic) mitochondria, by spreading from the inner membrane chamber as the proton carrier returns to the mitochondrial matrix, where it ionizes once again to release the proton. Aspirin buffer and transport protons. When high doses are given, it may actually cause a fever, because heat is released from the electron transport chain, as opposed to the antipyretic action of aspirin seen with lower doses. In addition, aspirin induces the formation of NO-radicals in the body, which has been shown in mice to have an independent mechanism to reduce inflammation. This reduces leukocyte adhesion is an important step in the immune response to infection; However, the evidence is not enough to show aspirin helps fight infection. The latest data also shows salicylic acid and its derivatives modulating signals via NF - B. NF-? B, a complex transcription factor, plays a central role in many biological processes, including inflammation.
Aspirin is easily broken down in the body into salicylic acid, which in itself has anti-inflammatory, antipyretic, and analgesic effects. In 2012, salicylic acid was found to activate AMP-activated protein kinase, which has been suggested as a possible explanation for some effects of salicylic acid and aspirin. The acetyl portion of the aspirin molecule has its own target. Acetylation of cellular proteins is a well established phenomenon in the regulation of protein function at post-translational level. Aspirin is able to acetylate several other targets besides COX isoenzymes. This acetylation reaction can explain many of the unexplained effects of aspirin.
Pharmacokinetics
Acetylsalicylic acid is a weak acid, and is very slightly ionized in the stomach after oral administration. Acetylsalicylic acid is rapidly absorbed through the cell membrane under acidic conditions of the stomach. The increase in pH and larger surface area of ​​the small intestine causes aspirin to be absorbed more slowly there, as more ionized. Because of the formation of concretion, aspirin is absorbed more slowly during overdose, and plasma concentrations may continue to rise up to 24 hours after consumption.
Approximately 50-80% of salicylates in the blood are bound to albumin protein, while the remainder remain active, ionized; protein binding depends on concentration. Saturation of the binding site causes more free salicylate and increased toxicity. The volume of distribution is 0.1-0.2 L/kg. Acidosis increases the volume of distribution due to increased penetration of salicylate tissue.
As much as 80% therapeutic dose of salicylic acid is metabolized in the liver. Conjugations with glycine form salicylic acid, and with glucuronic acid forming two different glucuronide esters. The conjugate with the whole acetyl group is referred to as acyl glucuronate ; deacetylated conjugate is phenolic glucuronide . This metabolic pathway has only limited capacity. A small amount of salicylic acid is also dihydroxylated to gentisic acid. With large salicylate doses, the kinetics switches from first to zero, as the metabolic pathway becomes saturated and renal excretion becomes increasingly important.
Salicylates are excreted mainly by the kidneys as salicylic acid (75%), free salicylic acid (10%), phenol salicylate (10%), and acyl glucuronide (5%), gentric acid (& lt; 1%), and 2, 3-dihydroxybenzoate. When small doses (less than 250 mg in adults) are ingested, all pathways are continued by first-order kinetics, with half-life elimination time of 2.0 hours to 4.5 hours. When higher doses of salicylate are ingested (more than 4 g), the half-life becomes longer (15 h to 30 h), since the biotransformation pathway associated with salicylic acid formation and salicyl phenolic glucuronate becomes saturated. The excretion of renal salicylate acid becomes increasingly important as the metabolic pathway becomes saturated, as it is very sensitive to changes in urine pH. A 10 to 20-fold increase in renal clearance occurs when the urinary pH increases from 5 to 8. The use of urinary alkalinization exploits certain aspects of salicylate elimination.
History
Drugs made from willows and other salicylic-rich plants appear on clay tablets from ancient Sumeria and Papers Ebers from ancient Egypt. Hippocrates refers to the use of salicylic tea to reduce fever around 400 BC, and is part of Western pharmacopoeia medicine in classical and medieval antiquity. The bark extract became known for its specific effects on fever, pain and inflammation in the mid-eighteenth century. By nineteenth century pharmacists experimenting with and prescribing various chemicals related to salicylic acid, the active component of willow extract.
In 1853, chemist Charles FrÃÆ' © dà © Ã… © ric Gerhardt treated sodium salicylate with acetyl chloride to produce acetylsalicylic acid for the first time; in the second half of the nineteenth century, other academic chemists established the chemical structure of the compound and devised a more efficient method of synthesis. In 1897, scientists at the Bayer drug and dye company began to investigate acetylsalicylic acid as a less irritating substitute for standard general salicylate drugs, and identified a new way to synthesise it. By 1899, Bayer had nicknamed this drug aspirin and sold it all over the world. The word Aspirin is the Bayer brand name, not the generic name of the drug; however, Bayer's rights to trademarks are lost or sold in many countries. The popularity of Aspirin grew in the first half of the twentieth century which led to fierce competition with the proliferation of brands and aspirin products.
The popularity of Aspirin decreased after the development of acetaminophen/paracetamol in 1956 and ibuprofen in 1962. In the 1960s and 1970s, John Vane and others discovered the basic mechanisms of aspirin effect, while clinical trials and other studies from the 1960s until the 1980s determined the efficacy of aspirin as an anti-clotting agent that reduced the risk of clotting diseases. The initial major study on the use of low-dose aspirin to prevent heart attacks published in the 1970s and 1980s helped spur reforms in clinical research ethics and guidelines for research on US human and legal subjects, and is often cited as a clinical example of a pilot involving only men, but from which people draw general conclusions that do not apply to women.
The sale of Aspirin was revived in the last decade of the 20th century, and remains strong in the 21st century with widespread use as a preventive treatment for heart attacks and strokes.
Trademark
Bayer lost the trademark for Aspirin in the United States in 1918 for failing to use a name for its own product and has for years allowed the use of "Aspirin" by other manufacturers. Today, aspirin is a generic trademark in many countries. Aspirin, with capital "A", remains a registered trademark of Bayer in Germany, Canada, Mexico, and in more than 80 other countries, for acetylsalicylic acid in all markets, but using different packaging and physical aspects for each.
Compendium Status
- Pharmacopoeia United States
- English Pharmacopoeia
Veterinary
Aspirin is sometimes used in veterinary medicine as an anticoagulant or to relieve pain associated with musculoskeletal inflammation or osteoarthritis. Aspirin should only be administered to animals under the direct supervision of veterinarians, as adverse effects - including gastrointestinal problems - are common. Overdose of aspirin in any species can lead to salicylate poisoning, characterized by bleeding, seizures, coma, and even death.
Cat and dog
Dogs are better able to tolerate aspirin than cats. Cats metabolize aspirin slowly because they do not have a glucuronide conjugate that helps in the excretion of aspirin, making it potentially toxic if doses are not given properly. No clinical signs of toxicosis occur when the cat is given aspirin 25 mg/kg every 48 hours for 4 weeks, but the recommended dose for relieving pain and fever and for treating catastrophic disease in cats is 10 mg/kg every 48 hours for allows for metabolism.
Cow and horse
Aspirin has shown some promise in the treatment of laminitis in horses.
References
External links
- Aspirin in Curlie (based on DMOZ)
- US. National Drug Library: Drug Information Portal - Aspirin
- CDC - NIOSH A Pocket Guide for Chemical Hazards - Acetyl Salicylic Acid
- Take two: Aspirin, New use and new dangers are still discovered when aspirin enters the 2nd century. Shauna Roberts, American Chemical Society
- Ling, Greg (2005). "Aspirin". How Items Created . 1 . Thomson Gale.
Source of the article : Wikipedia
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