Rab Ne Bana Di Jodi and Aspirin: Difference between pages

Aspirin
Clinical data
Other names	2-acetyloxybenzoic acid; 2-(acetyloxy)benzoic acid; acetylsalicylate; acetylsalicylic acid; O-acetylsalicylic acid
Pregnancy; category	AU: C; ;
Routes of; administration	Most commonly oral, also rectal. Lysine acetylsalicylate may be given IV or IM
ATC code	A01AD05 (WHO) B01AC06 (WHO), N02BA01 (WHO);
Legal status
Legal status	AU: Unscheduled; UK: General sales list (GSL, OTC); US: OTC;
Pharmacokinetic data
Bioavailability	Rapidly and completely absorbed
Protein binding	99.6%
Metabolism	Hepatic
Elimination half-life	300–650 mg dose: 3.1–3.2hrs; 1 g dose: 5 hours; 2 g dose: 9 hours
Excretion	Renal
Identifiers
	IUPAC name 2-ethanoylhydroxybenzoic acid;
CAS Number	50-78-2;
PubChem CID	2244;
DrugBank	APRD00264;
ChemSpider	2157;
CompTox Dashboard (EPA)	DTXSID5020108 ;
ECHA InfoCard	100.000.059
Chemical and physical data
Formula	C9H8O4
Molar mass	180.160 g/mol g·mol−1
3D model (JSmol)	Interactive image;
Density	1.40 g/cm3
Melting point	135 °C (275 °F)
Boiling point	140 °C (284 °F) (decomposes)
Solubility in water	10 mg/mL (20 °C)
	SMILES CC(=O)Oc1ccccc1C(=O)O;

Content deleted Content added

VisualWikitext

Inline

Revision as of 13:08, 12 October 2008

Aspirin, or acetylsalicylic acid (A.S.A.) (/əˌsɛtɨlsælɨˌsɪlɨk ˈæsɨd/), is a salicylate drug, often used as an analgesic to relieve minor aches and pains, as an antipyretic to reduce fever, and as an anti-inflammatory medication.

In countries where Aspirin is a registered trademark owned by Bayer, the generic term is "A.S.A."

Aspirin also has an antiplatelet or "anti-clotting" effect and is used in long-term, low doses to prevent heart attacks, strokes and blood clot formation in people at high risk for developing blood clots.^[1] It has also been established that low doses of aspirin may be given immediately after a heart attack to reduce the risk of another heart attack or of the death of cardiac tissue.^[2]^[3]

The main undesirable side effects of aspirin are gastrointestinal—ulcers and stomach bleeding—and tinnitus, especially in higher doses. In children under 19 years of age, aspirin is no longer used to control flu-like symptoms or the symptoms of chickenpox, due to the risk of Reye's syndrome.^[4]

Aspirin was the first-discovered member of the class of drugs known as non-steroidal anti-inflammatory drugs (NSAIDs), not all of which are salicylates, although they all have similar effects and most have some mechanism of action which involves non-selective inhibition of the enzyme cyclooxygenase. Today, aspirin is one of the most widely used medications in the world, with an estimated 40,000 metric tons of it being consumed each year.^[5]

History

Medicines containing derivatives of salicylic acid, structurally similar to aspirin, have been in medical use since ancient times. Salicylate-rich willow bark extract became recognized for its specific effects on fever, pain and inflammation in the mid-eighteenth century. By the nineteenth century pharmacists were experimenting with and prescribing a variety of chemicals related to salicylic acid, the active component of willow extract.

A French chemist, Charles Frederic Gerhardt, was the first to prepare acetylsalicylic acid (named aspirin in 1899) in 1853. In the course of his work on the synthesis and properties of various acid anhydrides, he mixed acetyl chloride with a sodium salt of salicylic acid (sodium salicylate). A vigorous reaction ensued, and the resulting melt soon solidified.^[6] Since no structural theory existed at that time, Gerhardt called the compound he obtained "salicylic-acetic anhydride" (wasserfreie Salicylsäure-Essigsäure). This preparation of aspirin ("salicylic-acetic anhydride") was one of the many reactions Gerhardt conducted for his paper on anhydrides, and he did not pursue it further.

Advertisement for Aspirin, Heroin, Lycetol, Salophen

Six years later, in 1859, von Gilm obtained analytically pure acetylsalicylic acid (which he called "acetylierte Salicylsäure", acetylated salicylic acid) by a reaction of salicylic acid and acetyl chloride.^[7] In 1869 Schröder, Prinzhorn and Kraut repeated both Gerhardt's (from sodium salicylate) and von Gilm's (from salicylic acid) syntheses and concluded that both reactions gave the same compound—acetylsalicylic acid. They were first to assign to it the correct structure with the acetyl group connected to the phenolic oxygen.^[8]

In 1897, scientists at the drug and dye firm Bayer began investigating acetylsalicylic acid as a less-irritating replacement for standard common salicylate medicines. By 1899, Bayer had dubbed this drug Aspirin and was selling it around the world.^[9]The name Aspirin is derived from A = Acetyl and "Spirsäure" = an old (German) name for salicylic acid.^[10] Aspirin's popularity grew over the first half of the twentieth century, spurred by its effectiveness in the wake of Spanish flu pandemic of 1918, and aspirin's profitability led to fierce competition and the proliferation of aspirin brands and products, especially after the American patent held by Bayer expired in 1917.^[11]^[12]

As part of war reparations following Germany's surrender after World War I, Aspirin lost its status as a registered trademark in France, United Kingdom and the United States where it became a generic name.^[13] Aspirin remains a registered trademark of Bayer in Germany and in over 80 other countries.^[14]

Aspirin's popularity declined after the market releases of paracetamol (acetaminophen) in 1956 and ibuprofen in 1969.^[15] In the 1960s and 1970s, John Vane and others discovered the basic mechanism of aspirin's effects, while clinical trials and other studies from the 1960s to the 1980s established aspirin's efficacy as an anti-clotting agent that reduces the risk of clotting diseases.^[16] Aspirin sales revived considerably in the last decades of the twentieth century, and remain strong in the twenty-first, thanks to widespread use as a preventive treatment for heart attacks and strokes.^[17]

Therapeutic uses

Aspirin is one of the most frequently used drugs in the treatment of mild to moderate pain, including that of migraines and fever.^[18]^[19] It is often combined with other non-steroidal anti-inflammatory drugs and opioid analgesics in the treatment of moderate to severe pain.^[20]

In high doses, aspirin and other salicylates are used in the treatment of rheumatic fever, rheumatic arthritis, and other inflammatory joint conditions. In lower doses, aspirin also has properties as an inhibitor of platelet aggregation, and has been shown to decrease the incidence of transient ischemic attacks and unstable angina in men, and can be used prophylactically. It is also used in the treatment of pericarditis, coronary artery disease, and acute myocardial infarction.^[21]^[22] Low doses of aspirin are also recommended for the prevention of stroke, and myocardial infarction in patients with either diagnosed coronary artery disease or who have an elevated risk of cardiovascular disease.

Experimental uses

Aspirin has been theorized to reduce cataract formation in diabetic patients, but one study showed it was ineffective for this purpose.^[23] The role of aspirin in reducing the incidence of many forms of cancer has also been widely studied. In several studies, aspirin use did not reduce the incidence of prostate cancer.^[24]^[25] Its effects on the incidence of pancreatic cancer are mixed; one study published in 2004 found a statistically significant increase in the risk of pancreatic cancer among women,^[26] while a meta-analysis of several studies, published in 2006, found no evidence that aspirin or other NSAIDs are associated with an increased risk for the disease.^[27] The drug may be effective in reduction of risk of various cancers, including those of the colon,^[28]^[29]^[30]^[31] lung,^[32]^[33] and possibly the upper GI tract, though some evidence of its effectiveness in preventing cancer of the upper GI tract has been inconclusive.^[34]^[35]^[34] Its preventative effect against adenocarcinomas may be explained by its inhibition of COX-2 enzymes expressed in them.^[36] An older study^{[citation needed]} claimed that aspirin may reduce the neurotoxicity of THC, the active drug in cannabis. However, this theory has been discredited, as newer studies^{[citation needed]} indicate THC to be neuroprotective rather than neurotoxic.

Veterinary uses

Aspirin has been used to treat pain and arthritis in veterinary medicine, primarily in cats and dogs, although it is often not recommended for this purpose, as there are newer medications available with fewer side effects in these animals. Dogs, for example, are particularly susceptible to the gastrointestinal side effects associated with salicylates.^[37] Horses have also been given aspirin for pain relief, although it is not commonly used due to its relatively short-lived analgesic effects. Horses are also fairly sensitive to the gastrointestinal side effects. Nevertheless, it has shown promise in its use as an anticoagulant, mostly in cases of laminitis.^[38] Aspirin should only be used in animals under the direct supervision of a veterinarian.

Mechanism of action

In 1971, British pharmacologist John Robert Vane, then employed by the Royal College of Surgeons in London, showed that aspirin suppressed the production of prostaglandins and thromboxanes.^[39]^[40] For this discovery, he was awarded both a Nobel Prize in Physiology or Medicine in 1982 and a knighthood.

Aspirin's ability to suppress the production of prostaglandins and thromboxanes is due to its irreversible inactivation of the cyclooxygenase (COX) enzyme. Cyclooxygenase is required for prostaglandin and thromboxane synthesis. Aspirin acts as an acetylating agent where an acetyl group is covalently attached to a serine residue in the active site of the COX enzyme. This makes aspirin different from other NSAIDs (such as diclofenac and ibuprofen), which are reversible inhibitors.

Low-dose, long-term aspirin use irreversibly blocks the formation of thromboxane A₂ in platelets, producing an inhibitory effect on platelet aggregation. This anticoagulant property makes aspirin useful for reducing the incidence of heart attacks.^[41] 40 mg of aspirin a day is able to inhibit a large proportion of maximum thromboxane A₂ release provoked acutely, with the prostaglandin I2 synthesis being little affected; however, higher doses of aspirin are required to attain further inhibition.^[42]

Prostaglandins are local hormones produced in the body and have diverse effects in the body, including the transmission of pain information to the brain, modulation of the hypothalamic thermostat, and inflammation. Thromboxanes are responsible for the aggregation of platelets that form blood clots. Heart attacks are primarily caused by blood clots, and low doses of aspirin are seen as an effective medical intervention for acute myocardial infarction. The major side-effect of this is that because the ability of blood to clot is reduced, excessive bleeding may result from the use of aspirin.

There are at least two different types of cyclooxygenase: COX-1 and COX-2. Aspirin irreversibly inhibits COX-1 and modifies the enzymatic activity of COX-2. Normally COX-2 produces prostanoids, most of which are pro-inflammatory. Aspirin-modified COX-2 produces lipoxins, most of which are anti-inflammatory. Newer NSAID drugs called COX-2 selective inhibitors have been developed that inhibit only COX-2, with the intent to reduce the incidence of gastrointestinal side-effects.^[5]

However, several of the new COX-2 selective inhibitors, such as Vioxx, have been recently withdrawn, after evidence emerged that COX-2 inhibitors increase the risk of heart attack. It is proposed that endothelial cells lining the microvasculature in the body express COX-2, and, by selectively inhibiting COX-2, prostaglandins (specifically PGI2; prostacyclin) are downregulated with respect to thromboxane levels, as COX-1 in platelets is unaffected. Thus, the protective anti-coagulative effect of PGI2 is decreased, increasing the risk of thrombus and associated heart attacks and other circulatory problems. Since platelets have no DNA, they are unable to synthesize new COX once aspirin has irreversibly inhibited the enzyme, an important difference with reversible inhibitors.

Furthermore, aspirin has been shown to have at least three additional modes of action. It uncouples oxidative phosphorylation in cartilaginous (and hepatic) mitochondria, by diffusing from the inner membrane space as a proton carrier back into the mitochondrial matrix, where it ionizes once again to release protons.^[43] In short, aspirin buffers and transports the protons. When high doses of aspirin are given, aspirin may actually cause fever due to the heat released from the electron transport chain, as opposed to the antipyretic action of aspirin seen with lower doses. Additionally, aspirin induces the formation of NO-radicals in the body, which have been shown in mice to have an independent mechanism of reducing inflammation. This reduced leukocyte adhesion, which is an important step in immune response to infection; however, there is currently insufficient evidence to show that aspirin helps to fight infection.^[44] More recent data also suggests that salicylic acid and its derivatives modulate signaling through NF-κB.^[45] NF-κB is a transcription factor complex that plays a central role in many biological processes, including inflammation.

Chemistry

Aspirin is an acetyl derivative of salicylic acid that is a white, crystalline, weakly acidic substance, with melting point 135°C. Acetylsalicylic acid decomposes rapidly in solutions of ammonium acetate or of the acetates, carbonates, citrates or hydroxides of the alkali metals. Acetylsalicylic acid is stable in dry air, but gradually hydrolyses in contact with moisture to acetic and salicylic acids. In solution with alkalis, the hydrolysis proceeds rapidly and the clear solutions formed may consist entirely of acetate and salicylate.^[46]

Synthesis

The synthesis of aspirin is classified as an esterification reaction, where the alcohol group from the salicylic acid reacts with an acid derivative (acetic anhydride), yielding aspirin and acetic acid as a byproduct. Small amounts of sulfuric acid (and occasionally phosphoric acid) are used as a catalyst. This method is commonly employed in undergraduate teaching labs.^[47]

Formulations containing high concentrations of aspirin often smell like vinegar.^[48] This is because aspirin can decompose in moist conditions, yielding salicylic acid and ethanoic acid.^[49]

The acid dissociation constant (pK_a) for acetylsalicylic acid is 3.5 at 25 °C.^[50]

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 are receiving regulatory approval for only a single crystal form or polymorph. For a long time, only one crystal structure for aspirin was known, although there had been indications that aspirin might have a second crystalline form since the 1960s. The elusive second polymorph was first discovered by Vishweshwar and coworkers in 2005,^[51] and fine structural details were given by Bond et al.^[52] A new crystal type was found after attempted co-crystallization of aspirin and levetiracetam from hot acetonitrile. The form II is only stable at 100 K and reverts back to form I at ambient temperature. In the (unambiguous) form I, two salicylic molecules form centrosymmetric dimers through the acetyl groups with the (acidic) methyl proton to carbonyl hydrogen bonds, and in the newly claimed form II, each salicylic molecule forms the same hydrogen bonds with two neighboring molecules instead of one. With respect to the hydrogen bonds formed by the carboxylic acid groups both polymorphs form identical dimer structures.

Pharmacokinetics

Salicylic acid is a weak acid, and very little of it is ionized in the stomach after oral administration. Acetylsalicylic acid is poorly soluble in the acidic conditions of the stomach, which can delay absorption of high doses for 8 to 24 hours. In addition to the increased pH of the small intestine, aspirin is rapidly absorbed there due to the increased surface area, which in turn allows more of the salicylate to dissolve. Due to the issue of solubility, however, aspirin is absorbed much more slowly during overdose, and plasma concentrations can continue to rise for up to 24 hours after ingestion.^[53]^[54]^[55]

About 50–80% of salicylate in the blood is bound by protein while the rest remains in the active, ionized state; protein binding is concentration-dependent. Saturation of binding sites leads to more free salicylate and increased toxicity. The volume of distribution is 0.1–0.2 l/kg. Acidosis increases the volume of distribution because of enhancement of tissue penetration of salicylates.^[55]

As much as 80% of therapeutic doses of salicylic acid is metabolized in the liver. Conjugation with glycine forms salicyluric acid and with glucuronic acid forms salicyl acyl and phenolic glucuronide. These metabolic pathways have only a limited capacity. Small amounts of salicylic acid are also hydroxylated to gentisic acid. With large salicylate doses, the kinetics switch from first order to zero order, as metabolic pathways become saturated and renal excretion becomes increasingly important.^[55]

Salicylates are excreted mainly by the kidneys as salicyluric acid (75%), free salicylic acid (10%), salicylic phenol (10%) and acyl (5%) glucuronides, and gentisic acid (< 1%). When small doses (less than 250 mg in an adult) are ingested, all pathways proceed by first order kinetics, with an elimination half-life of about 2 to 4.5 hours.^[56]^[57] When higher doses of salicylate are ingested (more than 4 g), the half-life becomes much longer (15-30 hours)^[58] because the biotransformation pathways concerned with the formation of salicyluric acid and salicyl phenolic glucuronide become saturated.^[59] Renal excretion of salicylic acid becomes increasingly important as the metabolic pathways become saturated, because it is extremely sensitive to changes in urinary pH. There is a 10 to 20 fold increase in renal clearance when urine pH is increased from 5 to 8. The use of urinary alkalinization exploits this particular aspect of salicylate elimination.^[60]

Contraindications and resistance

Aspirin should be avoided by those known to be allergic to ibuprofen or naproxen,^[61]^[62] or to have salicylate intolerance^[63]^[64] or a more generalized drug intolerance to NSAIDs, and caution should be exercised in those with asthma or NSAID-precipitated bronchospasm. Due to its effect on the stomach lining, manufacturers recommend that patients with kidney disease, peptic ulcers, mild diabetes, gout or gastritis talk to their doctors before using aspirin.^[61]^[65] Even if none of these conditions are present, there is still an increased risk of stomach bleeding when aspirin is taken with alcohol or warfarin.^[61]^[62] Patients with hemophilia or other bleeding tendencies should not take aspirin or other salicylates.^[61]^[65] Aspirin is known to cause hemolytic anemia in people who have the genetic disease glucose-6-phosphate dehydrogenase deficiency (G6PD), particularly in large doses and depending on the severity of the disease.^[66]^[67] Aspirin should not be given to children or adolescents to control cold or influenza symptoms as this has been linked with Reye's syndrome.^[4] Use of aspirin during Dengue Fever is not recommended due to increased bleeding tendency.^[68]

For some people, aspirin does not have as strong an effect on platelets as for others, an effect known as aspirin resistance or insensitivity. One study has suggested that women are more likely to be resistant than men^[69]^[70] and a different, aggregate study of 2,930 patients found 28% to be resistant.^[71]

Adverse effects

Gastrointestinal side effects

Aspirin use has been shown to increase the risk of gastrointestinal bleeding.^[72] Although some enteric coated formulations of aspirin are advertised as being "gentle to the stomach", in one study enteric coating did not seem to reduce this risk.^[72] Combining aspirin with other NSAIDs has also been shown to further increase this risk.^[72] Using aspirin in combination with clopidogrel or warfarin also increases the risk of upper GI bleeding.^[73]

Central effects

Large doses of salicylate, a metabolite of aspirin, have been proposed to cause tinnitus, based on the experiments in rats, via the action on arachidonic acid and NMDA receptors cascade.^[74]

Pediatrics

Reye's syndrome can occur when children or pediatric patients are given aspirin for a fever or other illnesses or infections. In one study, 213 patients under the age of 18 were reported for Reye's syndrome from the nationwide Reye's syndrome surveillance system. Out of 213 patients 211 had known that had another antecedent illness: 89% reported being ill (severe vomiting, mental strain, respiratory illness, vericella or gastrointestinal illness) two weeks before onset of Reye's syndrome. Salicylate levels, the active acid in aspirin, were present in 162 of the 213 patients. ^[75]

Reye's syndrome is due to fatty deterioration of liver cells. In another study, 12 livers were obtained from children who had died from Reye's syndrome, and another liver from a child who died of accidental causes was used as a control. The autopsy stated in seven of the 12 livers, micro vesicular fatty change was present.^[76]

Other effects

Aspirin can cause prolonged bleeding after operations for up to 10 days. In one study, thirty patients were observed after their various surgeries. Twenty of the thirty patients had to have an additional unplanned operation because of postoperative bleeding.^[77] This diffuse bleeding was associated with aspirin alone or in combination with another NSAID in 19 out of the 20 who had to have another operation due to bleeding after their operation. The average recovery time for the second operation was 11 days.

Aspirin can induce angioedema in some people. In one study, angioedema appeared 1-6 hours after ingesting aspirin in some of the patients participating in the study. However, when the aspirin was taken alone it did not cause angioedema in these patients; the aspirin was either taken in combination with another NSAID-induced drug when angioedema appeared.^[78]

Interactions

Aspirin is known to interact with other drugs. For example, acetazolamide and ammonium chloride have been known to enhance the intoxicating effect of salicyclates, and alcohol also enhances the gastrointestinal bleeding associated with these types of drugs as well.^[61]^[62] Aspirin is known to displace a number of drugs from protein binding sites in the blood, including the anti-diabetic drugs tolbutamide and chlorpropamide, the immunosuppressant methotrexate, phenytoin, probenecid, valproic acid (as well as interfering with beta oxidation, an important part of valproate metabolism) and any nonsteroidal anti-inflammatory drug. Corticosteroids may also reduce the concentration of aspirin. The pharmacological activity of spironolactone may be reduced by taking aspirin, and aspirin is known to compete with Penicillin G for renal tubular secretion.^[79] Aspirin may also inhibit the absorption of vitamin C.^[80]^[81]^[82]

Dosage

For adults doses are generally taken four times a day for fever or arthritis,^[83] with doses near the maximal daily dose used historically for the treatment of rheumatic fever.^[84] For the prevention of myocardial infarction in someone with documented or suspected coronary artery disease, much lower doses are taken once daily.^[83]

For those under 12 years of age, the dose previously varied with the age, but aspirin is no longer routinely used in children due to the association with Reye's syndrome; paracetamol (known as acetaminophen in North America) or other NSAIDs, such as ibuprofen, are now used instead. Kawasaki disease remains one of the few indications for aspirin use in children, with aspirin taken at dosages based on body weight, initially four times a day for up to two weeks and then at a lower dose once daily for a further six to eight weeks.^[85]

Overdose

Aspirin overdose can be acute or chronic. In acute poisoning, a single large dose is taken; in chronic poisoning, supratherapeutic doses are taken over a period of time. Acute overdose has a mortality rate of 2%. Chronic overdose is more commonly lethal with a mortality rate of 25%; chronic overdose may be especially severe in children.^[86]

Symptoms

Aspirin overdose has potentially serious consequences, sometimes leading to significant morbidity and death. Patients with mild intoxication frequently have nausea and vomiting, abdominal pain, lethargy, tinnitus, and dizziness. More significant symptoms occur in more severe poisonings and include hyperthermia, tachypnea, respiratory alkalosis, metabolic acidosis, hyperkalemia, hypoglycemia, hallucinations, confusion, seizure, cerebral edema, and coma. The most common cause of death following an aspirin overdose is cardiopulmonary arrest usually due to pulmonary edema.^[87]

Toxicity

The acutely toxic dose of aspirin is generally considered greater than 150 mg per kg of body mass.^[58] Moderate toxicity occurs at doses up to 300 mg/kg, severe toxicity occurs between 300 to 500 mg/kg, and a potentially lethal dose is greater than 500 mg/kg.^[88] This is the equivalent of many dozens of the common 325 mg tablets, depending on body weight. Chronic toxicity may occur following doses of 100 mg/kg per day for two or more days.^[88]

Treatment

All overdose patients should be conveyed to a hospital for assessment immediately. Initial treatment of an acute overdose includes gastric decontamination. This is achieved by administering activated charcoal, which adsorbs the aspirin in the gastrointestinal tract. Stomach pumps are no longer routinely used in the treatment of poisonings but are sometimes considered if the patient has ingested a potentially lethal amount less than 1 hour previously.^[89] Inducing emesis with syrup of ipecac is not recommended.^[58] Repeated doses of charcoal have been proposed to be beneficial in aspirin overdose;^[90] although, one study found that repeat dose charcoal might not be of significant value.^[91] However, most clinical toxicologists will administer additional charcoal if serum salicylate levels are increasing.

Patients are monitored until their peak salicylate blood level has been determined.^[60] Blood levels are usually assessed four hours after ingestion and then every two hours after that to determine the maximum level. Maximum levels can be used as a guide to toxic effects expected.^[92]

There is no antidote to salicylate poisoning. Monitoring of biochemical parameters such as electrolytes, liver and kidney function, urinalysis, and complete blood count is undertaken along with frequent checking of salicylate and blood sugar levels. Arterial blood gas assessments are performed to test for respiratory alkalosis and metabolic acidosis. Patients are monitored and often treated according to their individual symptoms, patients may be given intravenous potassium chloride to counteract hypokalemia, glucose to restore blood sugar levels, benzodiazepines for any seizure activity, fluids for dehydration, and importantly sodium bicarbonate to restore the blood's sensitive pH balance. Sodium bicarbonate also has the effect of increasing the pH of urine, which in turn increases the elimination of salicylate. Additionally, hemodialysis can be implemented to enhance the removal of salicylate from the blood. Hemodialysis is usually used in severely poisoned patients; for example, patients with significantly high salicylate blood levels, significant neurotoxicity (agitation, coma, convulsions), renal failure, pulmonary edema, or cardiovascular instability are hemodialyzed.^[60] Hemodialysis also has the advantage of restoring electrolyte and acid-base abnormalities while removing salicylate;^[60] hemodialysis is often life-saving in severely ill patients.

Epidemiology

In the later part of the 20th century the number of salicylate poisonings has declined mainly due to the popularity of other over-the-counter analgesics such as paracetamol (acetaminophen). Fifty-two deaths involving single-ingredient aspirin were reported in the United States in 2000. However, in all but three cases, the reason for the ingestion of lethal doses was intentional, predominantly suicides.^[93]

References

^ Lewis, H D (1983-08-18). "Protective effects of aspirin against acute myocardial infarction and death in men with unstable angina. Results of a Veterans Administration Cooperative Study". The New England journal of medicine. 309 (7): 396–403. ISSN 0028-4793. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
^ Julian, D G (1996-09-24). "A comparison of aspirin and anticoagulation following thrombolysis for myocardial infarction (the AFTER study): a multicentre unblinded randomised clinical trial". BMJ. 313 (7070). British Medical Journal: 1429–1431. PMID 8973228. Retrieved 2007-10-04. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
^ Krumholz, Harlan M. (1995-11-15). "Aspirin in the Treatment of Acute Myocardial Infarction in Elderly Medicare Beneficiaries : Patterns of Use and Outcomes". Circulation. 92 (10): 2841–2847. PMID 7586250. Retrieved 2008-05-15. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
^ ^a ^b Macdonald S (2002). "Aspirin use to be banned in under 16 year olds". BMJ. 325 (7371): 988. doi:10.1136/bmj.325.7371.988/c. PMC 1169585. PMID 12411346.
^ ^a ^b Warner, T. D. (2002-10-15). "Cyclooxygenase-3 (COX-3): filling in the gaps toward a COX continuum?". Proc Natl Acad Sci U S a. 99 (21): 13371–3. doi:10.1073/pnas.222543099. PMID 12374850. Retrieved 2008-05-08. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
^ Template:De icon Gerhardt C (1853). "Untersuchungen über die wasserfreien organischen Säuren". Annalen der Chemie und Pharmacie. 87: 149–179. doi:10.1002/jlac.18530870107.
^ Template:De icon von Gilm H (1859). "Acetylderivate der Phloretin- und Salicylsäure". Annalen der Chemie und Pharmacie. 112 (2): 180–185. doi:10.1002/jlac.18591120207.
^ Template:De icon Schröder, Prinzhorn, Kraut K (1869). "Uber Salicylverbindungen". Annalen der Chemie und Pharmacie. 150 (1): 1–20. doi:10.1002/jlac.18691500102.{{cite journal}}: CS1 maint: multiple names: authors list (link)
^ Jeffreys, Diarmuid (August 11, 2005). Aspirin: The Remarkable Story of a Wonder Drug. Bloomsbury USA. p. 73. ISBN 1582346003.
^ Ueber Aspirin. Pflügers Archiv : European journal of physiology, Volume: 84, Issue: 11-12 (March 1, 1901), pp: 527-546.
^ Jeffreys, Aspirin, pp. 136-142 and 151-152
^ http://www.history.com/this-day-in-history.do?action=VideoArticle&id=52415
^ http://www.ul.ie/~childsp/CinA/Issue59/TOC43_Aspirin.htm
^ http://www.aspirin.com/faq_en.html
^ Jeffreys, Aspirin, pp. 212-217
^ Jeffreys, Aspirin, pp. 226-231
^ Jeffreys, Aspirin, pp. 267-269
^ Aukerman G, Knutson D, Miser WF (2002). "Management of the acute migraine headache". Am Fam Phys. 66 (11): 2123–30. PMID 12484694.{{cite journal}}: CS1 maint: multiple names: authors list (link)
^ Addy, D P (1983-04-09). "Cold comfort for hot children". British Medical Journal (Clinical research ed.). 286 (6372).
^ Barkin, Robert (November/December 2001). "Acetaminophen, Aspirin, or Ibuprofen in Combination Analgesic Products". American Journal of Therapeutics. 8 (6): 433–42. doi:10.1097/00045391-200111000-00008. Retrieved 2008-05-02. {{cite journal}}: Check date values in: |date= (help)
^ Krumholz, HM (1995 November 15). "Aspirin in the treatment of acute myocardial infarction in elderly Medicare beneficiaries. Patterns of use and outcomes". Circulation. 92 (10): 2841–7. PMID 7586250. Retrieved 2008-05-02. {{cite journal}}: Check date values in: |date= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)
^ ISIS-2 Collaborative group (1988). "Randomized trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2". Lancet (2): 349–60. PMID 2899772.{{cite journal}}: CS1 maint: numeric names: authors list (link)
^ Chew EY, Williams GA, Burton TC, Barton FB, Remaley NA, Ferris FL (1992). "Aspirin effects on the development of cataracts in patients with diabetes mellitus. Early treatment diabetic retinopathy study report 16". Arch Ophthalmol. 110 (3): 339–42. PMID 1543449.{{cite journal}}: CS1 maint: multiple names: authors list (link)
^ Bosetti; et al. (2006). "Aspirin and the risk of prostate cancer". Eur J Cancer Prev. 15 (1): 43–5. doi:10.1097/01.cej.0000180665.04335.de. PMID 16374228. {{cite journal}}: Explicit use of et al. in: |author= (help)
^ Menezes; et al. (2006). "Regular use of aspirin and prostate cancer risk (United States)". Cancer Causes & Control. 17 (3): 251–6. doi:10.1007/s10552-005-0450-z. PMID 16489532. {{cite journal}}: Explicit use of et al. in: |author= (help)
^ Schernhammer; et al. (2004). "A Prospective Study of Aspirin Use and the Risk of Pancreatic Cancer in Women". J Natl Cancer Inst. 96 (1): 22–28. doi:10.1093/jnci/djh001. PMID 14709735. {{cite journal}}: Explicit use of et al. in: |author= (help)
^ Larsson SC, Giovannucci E, Bergkvist L, Wolk A (2006). "Aspirin and nonsteroidal anti-inflammatory drug use and risk of pancreatic cancer: a meta-analysis". Cancer Epidemiol. Biomarkers Prev. 15 (12): 2561–4. doi:10.1158/1055-9965.EPI-06-0574. PMID 17164387. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
^ Thun MJ, Namboodiri MM, Heath CW (1991). "Aspirin use and reduced risk of fatal colon cancer". N Engl J Med. 325 (23): 1593–6. PMID 1669840.{{cite journal}}: CS1 maint: multiple names: authors list (link)
^ Baron; et al. (2003). "A randomized trial of aspirin to prevent colorectal adenomas". N Engl J Med. 348 (10): 891–9. doi:10.1056/NEJMoa021735. PMID 12621133. {{cite journal}}: Explicit use of et al. in: |author= (help)
^ Chan; et al. (2004). "A Prospective Study of Aspirin Use and the Risk for Colorectal Adenoma". Ann Intern Med. 140 (3): 157–66. PMID 14757613. {{cite journal}}: Explicit use of et al. in: |author= (help)
^ Chan; et al. (2005). "Long-term Use of Aspirin and Nonsteroidal Anti-inflammatory Drugs and Risk of Colorectal Cancer". JAMA. 294 (8): 914–23. doi:10.1001/jama.294.8.914. PMID 16118381. {{cite journal}}: Explicit use of et al. in: |author= (help)
^ Akhmedkhanov; et al. (2002). "Aspirin and lung cancer in women". Br J cancer. 87 (11): 1337–8. doi:10.1038/sj.bjc.6600370. PMID 12085255. {{cite journal}}: Explicit use of et al. in: |author= (help)
^ Moysich KB, Menezes RJ, Ronsani A; et al. (2002). "Regular aspirin use and lung cancer risk". BMC Cancer. 2: 31. PMID 12453317. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link) Free full text
^ ^a ^b Jayaprakash, Vijayvel (2006-07-01). "Regular aspirin use and esophageal cancer risk". Int J Cancer. 119 (1): 202–7. doi:10.1002/ijc.21814. PMID 16450404. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
^ Bosetti; et al. (2003). "Aspirin use and cancers of the upper aerodigestive tract". Br J Cancer. 88 (5): 672–74. doi:10.1038/sj.bjc.6600820. PMID 12618872. {{cite journal}}: Explicit use of et al. in: |author= (help)
^ Wolff; et al. (1998). "Expression of cyclooxygenase-2 in human lung carcinoma". Cancer Research. 58 (22): 4997–5001. PMID 9823297. {{cite journal}}: Explicit use of et al. in: |author= (help)
^ Crosby, Janet Tobiassen (2006). "Veterinary Questions and Answers". About.com. Retrieved 2007-09-05.
^ Cambridge H, Lees P, Hooke RE, Russell CS (1991). "Antithrombotic actions of aspirin in the horse". Equine Vet J. 23 (2): 123–7. PMID 1904347.{{cite journal}}: CS1 maint: multiple names: authors list (link)
^ John Robert Vane (1971). "Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs". Nature - New Biology. 231 (25): 232–5. PMID 5284360.
^ Vane JR, Botting RM (2003). "The mechanism of action of aspirin" (PDF). Thromb Res. 110 (5–6): 255–8. doi:10.1016/S0049-3848(03)00379-7. PMID 14592543. {{cite journal}}: Unknown parameter |month= ignored (help)
^ "Aspirin in Heart Attack and Stroke Prevention". American Heart Association. Retrieved 2008-05-08.
^ Tohgi, H (1992). "Effects of low-to-high doses of aspirin on platelet aggregability and metabolites of thromboxane A2 and prostacyclin". Stroke. Vol 23: 1400–1403. PMID 1412574. {{cite journal}}: |volume= has extra text (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)
^ Somasundaram, S.; et al. (2000). "Uncoupling of intestinal mitochondrial oxidative phosphorylation and inhibition of cyclooxygenase are required for the development of NSAID-enteropathy in the rat". Aliment Pharmacol Ther. 14: 639–650. doi:10.1046/j.1365-2036.2000.00723.x. Retrieved 2008-05-28. {{cite journal}}: Explicit use of et al. in: |last= (help); Unknown parameter |doi_brokendate= ignored (|doi-broken-date= suggested) (help)
^ Mark J. Paul-Clark, Thong van Cao, Niloufar Moradi-Bidhendi, Dianne Cooper, and Derek W. Gilroy 15-epi-lipoxin A4–mediated Induction of Nitric Oxide Explains How Aspirin Inhibits Acute Inflammation J. Exp. Med. 200: 69-78; published online before print as 10.1084/jem.20040566
^ McCarty, MF (2006). "Preadministration of high-dose salicylates, suppressors of NF-kappaB activation, may increase the chemosensitivity of many cancers: an example of proapoptotic signal modulation therapy". Integr Cancer Ther. Vol 5 (3): 252–268. doi:10.1177/1534735406291499. PMID 16880431. {{cite journal}}: |volume= has extra text (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)
^ Reynolds EF (ed) (1982). Aspirin and similar analgesic and anti-inflammatory agents. Martindale, The Extra Pharmacopoeia 28 Ed, 234-82.
^ Palleros, Daniel R. (2000). Experimental Organic Chemistry. New York: John Wiley & Sons. p. 494. ISBN 0-471-28250-2.
^ Barrans, Richard. "Aspirin Aging". Newton BBS. Retrieved 2008-05-08.
^ Carstensen, J.T. (1985). "Decomposition of aspirin in the solid state in the presence of limited amounts of moisture". Journal of Pharmaceutical Sciences. 77 (4): 318–21. doi:10.1002/jps.2600770407. PMID 4032246. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)
^ "Acetylsalicylic acid". Jinno Laboratory, School of Materials Science, Toyohashi University of Technology. March 1 1996. Retrieved 2007-09-07. {{cite web}}: Check date values in: |date= (help)
^ Peddy Vishweshwar, Jennifer A. McMahon, Mark Oliveira, Matthew L. Peterson, and Michael J. Zaworotko (2005). "The Predictably Elusive Form II of Aspirin". J. Am. Chem. Soc. 127 (48): 16802–16803. doi:10.1021/ja056455b.{{cite journal}}: CS1 maint: multiple names: authors list (link)
^ Andrew D. Bond, Roland Boese, Gautam R. Desiraju (2007). "On the Polymorphism of Aspirin: Crystalline Aspirin as Intergrowths of Two "Polymorphic" Domains". Angewandte Chemie International Edition. 46 (4): 618–622. doi:10.1002/anie.200603373.{{cite journal}}: CS1 maint: multiple names: authors list (link)
^ Ferguson, RK (1970-08-17). "Death following self-poisoning with aspirin". Journal of the American Medical Association. PMID 5468267. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
^ Kaufman, FL (1970-04). "Darvon poisoning with delayed salicylism: a case report". Pediatrics. 49 (4): 610–1. PMID 5013423. {{cite journal}}: Check date values in: |date= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)
^ ^a ^b ^c Levy, G (1972-09-31). "Salicylate accumulation kinetics in man". New England Journal of Medicine. 287 (9): 430–2. PMID 5044917. {{cite journal}}: Check date values in: |date= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)
^ Hartwig, Otto H (1983-11-14). "Pharmacokinetic considerations of common analgesics and antipyretics". American Journal of Medicine. 75 (5A): 30–7. doi:10.1016/0002-9343(83)90230-9. PMC 1725844. PMID 6606362. {{cite journal}}: Cite has empty unknown parameter: |coauthors= (help)
^ Done, AK (1960-11). "Salicylate intoxication. Significance of measurements of salicylate in blood in cases of acute ingestion". Pediatrics: 800–7. PMID 13723722. {{cite journal}}: Check date values in: |date= (help); Cite has empty unknown parameter: |coauthors= (help)
^ ^a ^b ^c Chyka PA, Erdman AR, Christianson G, Wax PM, Booze LL, Manoguerra AS, Caravati EM, Nelson LS, Olson KR, Cobaugh DJ, Scharman EJ, Woolf AD, Troutman WG; Americal Association of Poison Control Centers; Healthcare Systems Bureau, Health Resources and Services Administration, Department of Health and Human Services. (2007). "Salicylate poisoning: an evidence-based consensus guideline for out-of-hospital management". Clin Toxicol (Phila). 45 (2): 95–131. doi:10.1080/15563650600907140. PMID 17364628.{{cite journal}}: CS1 maint: multiple names: authors list (link)
^ Prescott LF, Balali-Mood M, Critchley JA, Johnstone AF, Proudfoot AT (1982). "Diuresis or urinary alkalinisation for salicylate poisoning?". Br Med J (Clin Res Ed). 285 (6352): 1383–6. PMC 1500395. PMID 6291695. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
^ ^a ^b ^c ^d Dargan PI, Wallace CI, Jones AL. (2002). "An evidenced based flowchart to guide the management of acute salicylate (aspirin) overdose". Emerg Med J. 19 (3): 206–9. doi:10.1136/emj.19.3.206. PMC 1725844. PMID 11971828.{{cite journal}}: CS1 maint: multiple names: authors list (link)
^ ^a ^b ^c ^d ^e "Aspirin information from Drugs.com". Drugs.com. Retrieved 2008-05-08.
^ ^a ^b ^c "Oral Aspirin information". First DataBank. Retrieved 2008-05-08.
^ Raithel M, Baenkler HW, Naegel A; et al. (2005). "Significance of salicylate intolerance in diseases of the lower gastrointestinal tract" (PDF). J. Physiol. Pharmacol. 56 Suppl 5: 89–102. PMID 16247191. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
^ Senna GE, Andri G, Dama AR, Mezzelani P, Andri L (1995). "Tolerability of imidazole salycilate in aspirin-sensitive patients". Allergy Proc. 16 (5): 251–4. PMID 8566739.{{cite journal}}: CS1 maint: multiple names: authors list (link)
^ ^a ^b PDR® Guide to Over the Counter (OTC) Drugs, retrieved 2008-04-28.
^ G6PD (Glucose-6-Phosphate Dehydrogenase) Deficiency, University of Virginia, retrieved 2008-05-07
^ G6PD (Glucose-6-Phosphate Dehydrogenase) Deficiency, University of Texas Medical Branch, retrieved 2008-05-07
^ Dengue and Dengue Hemorrhagic Fever: Information for Health Care Practitioners, retrieved 2008-04-28
^ "Aspirin may be less effective heart treatment for women than men". University of Michigan. 2007-04-26. Retrieved 2007-09-09. {{cite news}}: Check date values in: |date= (help)
^ Dorsch MP, Lee JS, Lynch DR, Dunn SP, Rodgers JE, Schwartz T, Colby E, Montague D, Smyth SS (2007). "Aspirin Resistance in Patients with Stable Coronary Artery Disease with and without a History of Myocardial Infarction". Ann Pharmacother. 41 (May): 737. doi:10.1345/aph.1H621. PMID 17456544. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
^ "Increased risk of heart attack or stroke for patients who are resistant to aspirin". 2008-01-17. Retrieved 2008-01-20.
^ ^a ^b ^c Sørensen HT, Mellemkjaer L, Blot WJ; et al. (2000). "Risk of upper gastrointestinal bleeding associated with use of low-dose aspirin". Am. J. Gastroenterol. 95 (9): 2218–24. doi:10.1111/j.1572-0241.2000.02248.x. PMID 11007221. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
^ Delaney JA, Opatrny L, Brophy JM & Suissa S (2007). "Drug drug interactions between antithrombotic medications and the risk of gastrointestinal bleeding". CMAJ. 177 (4): 347–51. doi:10.1503/cmaj.070186. PMC 1942107. PMID 17698822. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
^ Guitton MJ, Caston J, Ruel J, Johnson RM, Pujol R, Puel JL (2003). "Salicylate induces tinnitus through activation of cochlear NMDA receptors". J. Neurosci. 23 (9): 3944–52. PMID 12736364. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
^ Rogers MF, Schonberger LB, Hurwitz ES & Rowley DL (1985). "National Reye syndrome surveillance, 1982". Pediatrics. 75 (2): 260–4. PMID 3969325. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
^ Rogan WJ, Yang GC & Kimbrough RD (1985). "Aflatoxin and Reye's syndrome: a study of livers from deceased cases". ArchEnviron Health. 40 (2): 91–5. PMID 4004347. {{cite journal}}: Unknown parameter |month= ignored (help)
^ Scher, K.S. (1996). "Unplanned reoperation for bleeding". Am Surg. 62 (1): 52–55. PMID 8540646. {{cite journal}}: Unknown parameter |month= ignored (help)
^ Berges-Gimeno MP & Stevenson DD (2004). "Nonsteroidal anti-inflammatory drug-induced reactions and desensitization". J Asthma. 41 (4): 375–84. doi:10.1081/JAS-120037650. PMID 15281324. {{cite journal}}: Unknown parameter |month= ignored (help)
^ Katzung (1998), p. 584.
^ Loh HS, Watters K & Wilson CW (1973). "The Effects of Aspirin on the Metabolic Availability of Ascorbic Acid in Human Beings". J Clin Pharmacol. 13 (11): 480–6. PMID 4490672.
^ Basu TK (1982). "Vitamin C-aspirin interactions". Int J Vitam Nutr Res Suppl. 23: 83–90. PMID 6811490. {{cite journal}}: Cite has empty unknown parameter: |month= (help)
^ Ioannides C, Stone AN, Breacker PJ & Basu TK (1982). "Impairment of absorption of ascorbic acid following ingestion of aspirin in guinea pigs". Biochem Pharmacol. 31 (24): 4035–8. doi:10.1016/0006-2952(82)90652-9. PMID 6818974. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
^ ^a ^b British National Formulary (45 ed.). British Medical Journal and Royal Pharmaceutical Society of Great Britain. 2003. {{cite book}}: Unknown parameter |month= ignored (help)
^ Aspirin monograph: dosages, etc
^ British National Formulary for Children. British Medical Journal and Royal Pharmaceutical Society of Great Britain. 2006.
^ Gaudreault P, Temple AR, Lovejoy FH Jr. (1982). "The relative severity of acute versus chronic salicylate poisoning in children: a clinical comparison". Pediatrics. 70 (4): 566–9. PMID 7122154.{{cite journal}}: CS1 maint: multiple names: authors list (link)
^ Thisted B, Krantz T, Stroom J, Sorensen MB. (1987). "Acute salicylate self-poisoning in 177 consecutive patients treated in ICU". Acta Anaesthesiol Scand. 31 (4): 312–6. PMID 3591255.{{cite journal}}: CS1 maint: multiple names: authors list (link)
^ ^a ^b Temple AR. (1981). "Acute and chronic effects of aspirin toxicity and their treatment". Arch Intern Med. 141 (3 Spec No): 364–9. doi:10.1001/archinte.141.3.364. PMID 7469627.
^ Vale JA, Kulig K; American Academy of Clinical Toxicology; European Association of Poisons Centres and Clinical Toxicologists. (2004). "Position paper: gastric lavage". J Toxicol Clin Toxicol. 42 (7): 933–43. doi:10.1081/CLT-200045006. PMID 15641639.{{cite journal}}: CS1 maint: multiple names: authors list (link)
^ Hillman RJ, Prescott LF. (1985). "Treatment of salicylate poisoning with repeated oral charcoal". Br Med J (Clin Res Ed). 291 (6507): 1472. PMID 3933714.
^ Kirshenbaum LA, Mathews SC, Sitar DS, Tenenbein M. (1990). "Does multiple-dose charcoal therapy enhance salicylate excretion?". Arch Intern Med. 150 (6): 1281–3. doi:10.1001/archinte.150.6.1281. PMID 2191636.{{cite journal}}: CS1 maint: multiple names: authors list (link)
^ Meredith TJ, Vale JA. (1986). "Non-narcotic analgesics. Problems of overdosage". Drugs. 32 (Suppl 4): 117–205. doi:10.2165/00003495-198600324-00013. PMID 3552583.
^ Litovitz TL, Klein-Schwartz W, White S, Cobaugh DJ, Youniss J, Omslaer JC, Drab A, Benson BE (2001). "2000 Annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System". Am J Emerg Med. 19 (5): 337–95. doi:10.1053/ajem.2001.25272. PMID 11555795.{{cite journal}}: CS1 maint: multiple names: authors list (link)

External links

DrugBank Aspirin Entry
NextBio Aspirin Entry
Reappraisal
An aspirin a day keeps the doctor away
Colour-enhanced scanning electron micrograph of aspirin crystals
Aspirin research in the 1990s
The History of Aspirin
Aspirin and heart disease
How Aspirin works
Molview from bluerhinos.co.uk See Aspirin in 3D
History of Aspro
The science behind aspirin
Take two: Aspirin, New uses and new dangers are still being discovered as aspirin enters its second century. Shauna Roberts, American Chemical Society
Ling, Greg (2005). "Aspirin". How Products are Made. Vol. 1. Thomson Gale.
A Gene Expression Omnibus entry of a genome-wide transcriptional expression data for bioactive small molecules (Aspirin among them)

Template:Link FA Template:Link FA

[1] Lewis, H D (1983-08-18). "Protective effects of aspirin against acute myocardial infarction and death in men with unstable angina. Results of a Veterans Administration Cooperative Study". The New England journal of medicine. 309 (7): 396–403. ISSN 0028-4793. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)

[anticoag-2] Julian, D G (1996-09-24). "A comparison of aspirin and anticoagulation following thrombolysis for myocardial infarction (the AFTER study): a multicentre unblinded randomised clinical trial". BMJ. 313 (7070). British Medical Journal: 1429–1431. PMID 8973228. Retrieved 2007-10-04. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)

[3] Krumholz, Harlan M. (1995-11-15). "Aspirin in the Treatment of Acute Myocardial Infarction in Elderly Medicare Beneficiaries : Patterns of Use and Outcomes". Circulation. 92 (10): 2841–2847. PMID 7586250. Retrieved 2008-05-15. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)

[BMJ2002-Macdonald-4] Macdonald S (2002). "Aspirin use to be banned in under 16 year olds". BMJ. 325 (7371): 988. doi:10.1136/bmj.325.7371.988/c. PMC 1169585. PMID 12411346.

[cox3article-5] Warner, T. D. (2002-10-15). "Cyclooxygenase-3 (COX-3): filling in the gaps toward a COX continuum?". Proc Natl Acad Sci U S a. 99 (21): 13371–3. doi:10.1073/pnas.222543099. PMID 12374850. Retrieved 2008-05-08. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)

[gerhardt-6] Template:De icon Gerhardt C (1853). "Untersuchungen über die wasserfreien organischen Säuren". Annalen der Chemie und Pharmacie. 87: 149–179. doi:10.1002/jlac.18530870107.

[gilm-7] Template:De icon von Gilm H (1859). "Acetylderivate der Phloretin- und Salicylsäure". Annalen der Chemie und Pharmacie. 112 (2): 180–185. doi:10.1002/jlac.18591120207.

[8] Template:De icon Schröder, Prinzhorn, Kraut K (1869). "Uber Salicylverbindungen". Annalen der Chemie und Pharmacie. 150 (1): 1–20. doi:10.1002/jlac.18691500102.{{cite journal}}: CS1 maint: multiple names: authors list (link)

[9] Jeffreys, Diarmuid (August 11, 2005). Aspirin: The Remarkable Story of a Wonder Drug. Bloomsbury USA. p. 73. ISBN 1582346003.

[10] Ueber Aspirin. Pflügers Archiv : European journal of physiology, Volume: 84, Issue: 11-12 (March 1, 1901), pp: 527-546.

[11] Jeffreys, Aspirin, pp. 136-142 and 151-152

[12] ttp://www.history.com/this-day-in-history.do?action=VideoArticle&id=52415

[13] ttp://www.ul.ie/~childsp/CinA/Issue59/TOC43_Aspirin.htm

[14] ttp://www.aspirin.com/faq_en.html

[15] Jeffreys, Aspirin, pp. 212-217

[16] Jeffreys, Aspirin, pp. 226-231

[17] Jeffreys, Aspirin, pp. 267-269

[18] Aukerman G, Knutson D, Miser WF (2002). "Management of the acute migraine headache". Am Fam Phys. 66 (11): 2123–30. PMID 12484694.{{cite journal}}: CS1 maint: multiple names: authors list (link)

[19] Addy, D P (1983-04-09). "Cold comfort for hot children". British Medical Journal (Clinical research ed.). 286 (6372).

[R_Barkin-20] Barkin, Robert (November/December 2001). "Acetaminophen, Aspirin, or Ibuprofen in Combination Analgesic Products". American Journal of Therapeutics. 8 (6): 433–42. doi:10.1097/00045391-200111000-00008. Retrieved 2008-05-02. {{cite journal}}: Check date values in: |date= (help)

[21] Krumholz, HM (1995 November 15). "Aspirin in the treatment of acute myocardial infarction in elderly Medicare beneficiaries. Patterns of use and outcomes". Circulation. 92 (10): 2841–7. PMID 7586250. Retrieved 2008-05-02. {{cite journal}}: Check date values in: |date= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)

[Lancet1988-ISIS2-22] ISIS-2 Collaborative group (1988). "Randomized trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2". Lancet (2): 349–60. PMID 2899772.{{cite journal}}: CS1 maint: numeric names: authors list (link)

[chew-23] Chew EY, Williams GA, Burton TC, Barton FB, Remaley NA, Ferris FL (1992). "Aspirin effects on the development of cataracts in patients with diabetes mellitus. Early treatment diabetic retinopathy study report 16". Arch Ophthalmol. 110 (3): 339–42. PMID 1543449.{{cite journal}}: CS1 maint: multiple names: authors list (link)

[24] Bosetti; et al. (2006). "Aspirin and the risk of prostate cancer". Eur J Cancer Prev. 15 (1): 43–5. doi:10.1097/01.cej.0000180665.04335.de. PMID 16374228. {{cite journal}}: Explicit use of et al. in: |author= (help)

[25] Menezes; et al. (2006). "Regular use of aspirin and prostate cancer risk (United States)". Cancer Causes & Control. 17 (3): 251–6. doi:10.1007/s10552-005-0450-z. PMID 16489532. {{cite journal}}: Explicit use of et al. in: |author= (help)

[26] Schernhammer; et al. (2004). "A Prospective Study of Aspirin Use and the Risk of Pancreatic Cancer in Women". J Natl Cancer Inst. 96 (1): 22–28. doi:10.1093/jnci/djh001. PMID 14709735. {{cite journal}}: Explicit use of et al. in: |author= (help)

[27] Larsson SC, Giovannucci E, Bergkvist L, Wolk A (2006). "Aspirin and nonsteroidal anti-inflammatory drug use and risk of pancreatic cancer: a meta-analysis". Cancer Epidemiol. Biomarkers Prev. 15 (12): 2561–4. doi:10.1158/1055-9965.EPI-06-0574. PMID 17164387. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)

[thun-28] Thun MJ, Namboodiri MM, Heath CW (1991). "Aspirin use and reduced risk of fatal colon cancer". N Engl J Med. 325 (23): 1593–6. PMID 1669840.{{cite journal}}: CS1 maint: multiple names: authors list (link)

[29] Baron; et al. (2003). "A randomized trial of aspirin to prevent colorectal adenomas". N Engl J Med. 348 (10): 891–9. doi:10.1056/NEJMoa021735. PMID 12621133. {{cite journal}}: Explicit use of et al. in: |author= (help)

[30] Chan; et al. (2004). "A Prospective Study of Aspirin Use and the Risk for Colorectal Adenoma". Ann Intern Med. 140 (3): 157–66. PMID 14757613. {{cite journal}}: Explicit use of et al. in: |author= (help)

[31] Chan; et al. (2005). "Long-term Use of Aspirin and Nonsteroidal Anti-inflammatory Drugs and Risk of Colorectal Cancer". JAMA. 294 (8): 914–23. doi:10.1001/jama.294.8.914. PMID 16118381. {{cite journal}}: Explicit use of et al. in: |author= (help)

[32] Akhmedkhanov; et al. (2002). "Aspirin and lung cancer in women". Br J cancer. 87 (11): 1337–8. doi:10.1038/sj.bjc.6600370. PMID 12085255. {{cite journal}}: Explicit use of et al. in: |author= (help)

[33] Moysich KB, Menezes RJ, Ronsani A; et al. (2002). "Regular aspirin use and lung cancer risk". BMC Cancer. 2: 31. PMID 12453317. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link) Free full text

[Asprin_upper_GI_cancer-34] Jayaprakash, Vijayvel (2006-07-01). "Regular aspirin use and esophageal cancer risk". Int J Cancer. 119 (1): 202–7. doi:10.1002/ijc.21814. PMID 16450404. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)

[35] Bosetti; et al. (2003). "Aspirin use and cancers of the upper aerodigestive tract". Br J Cancer. 88 (5): 672–74. doi:10.1038/sj.bjc.6600820. PMID 12618872. {{cite journal}}: Explicit use of et al. in: |author= (help)

[36] Wolff; et al. (1998). "Expression of cyclooxygenase-2 in human lung carcinoma". Cancer Research. 58 (22): 4997–5001. PMID 9823297. {{cite journal}}: Explicit use of et al. in: |author= (help)

[37] Crosby, Janet Tobiassen (2006). "Veterinary Questions and Answers". About.com. Retrieved 2007-09-05.

[CambridgeH-38] Cambridge H, Lees P, Hooke RE, Russell CS (1991). "Antithrombotic actions of aspirin in the horse". Equine Vet J. 23 (2): 123–7. PMID 1904347.{{cite journal}}: CS1 maint: multiple names: authors list (link)

[39] John Robert Vane (1971). "Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs". Nature - New Biology. 231 (25): 232–5. PMID 5284360.

[40] Vane JR, Botting RM (2003). "The mechanism of action of aspirin" (PDF). Thromb Res. 110 (5–6): 255–8. doi:10.1016/S0049-3848(03)00379-7. PMID 14592543. {{cite journal}}: Unknown parameter |month= ignored (help)

[41] "Aspirin in Heart Attack and Stroke Prevention". American Heart Association. Retrieved 2008-05-08.

[42] Tohgi, H (1992). "Effects of low-to-high doses of aspirin on platelet aggregability and metabolites of thromboxane A2 and prostacyclin". Stroke. Vol 23: 1400–1403. PMID 1412574. {{cite journal}}: |volume= has extra text (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)

[SomasundaramS-43] Somasundaram, S.; et al. (2000). "Uncoupling of intestinal mitochondrial oxidative phosphorylation and inhibition of cyclooxygenase are required for the development of NSAID-enteropathy in the rat". Aliment Pharmacol Ther. 14: 639–650. doi:10.1046/j.1365-2036.2000.00723.x. Retrieved 2008-05-28. {{cite journal}}: Explicit use of et al. in: |last= (help); Unknown parameter |doi_brokendate= ignored (|doi-broken-date= suggested) (help)

[44] Mark J. Paul-Clark, Thong van Cao, Niloufar Moradi-Bidhendi, Dianne Cooper, and Derek W. Gilroy 15-epi-lipoxin A4–mediated Induction of Nitric Oxide Explains How Aspirin Inhibits Acute Inflammation J. Exp. Med. 200: 69-78; published online before print as 10.1084/jem.20040566

[45] McCarty, MF (2006). "Preadministration of high-dose salicylates, suppressors of NF-kappaB activation, may increase the chemosensitivity of many cancers: an example of proapoptotic signal modulation therapy". Integr Cancer Ther. Vol 5 (3): 252–268. doi:10.1177/1534735406291499. PMID 16880431. {{cite journal}}: |volume= has extra text (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)

[46] Reynolds EF (ed) (1982). Aspirin and similar analgesic and anti-inflammatory agents. Martindale, The Extra Pharmacopoeia 28 Ed, 234-82.

[47] Palleros, Daniel R. (2000). Experimental Organic Chemistry. New York: John Wiley & Sons. p. 494. ISBN 0-471-28250-2.

[48] Barrans, Richard. "Aspirin Aging". Newton BBS. Retrieved 2008-05-08.

[49] Carstensen, J.T. (1985). "Decomposition of aspirin in the solid state in the presence of limited amounts of moisture". Journal of Pharmaceutical Sciences. 77 (4): 318–21. doi:10.1002/jps.2600770407. PMID 4032246. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)

[asaaciddissconst-50] "Acetylsalicylic acid". Jinno Laboratory, School of Materials Science, Toyohashi University of Technology. March 1 1996. Retrieved 2007-09-07. {{cite web}}: Check date values in: |date= (help)

[51] Peddy Vishweshwar, Jennifer A. McMahon, Mark Oliveira, Matthew L. Peterson, and Michael J. Zaworotko (2005). "The Predictably Elusive Form II of Aspirin". J. Am. Chem. Soc. 127 (48): 16802–16803. doi:10.1021/ja056455b.{{cite journal}}: CS1 maint: multiple names: authors list (link)

[52] Andrew D. Bond, Roland Boese, Gautam R. Desiraju (2007). "On the Polymorphism of Aspirin: Crystalline Aspirin as Intergrowths of Two "Polymorphic" Domains". Angewandte Chemie International Edition. 46 (4): 618–622. doi:10.1002/anie.200603373.{{cite journal}}: CS1 maint: multiple names: authors list (link)

[RK_Ferguson-53] Ferguson, RK (1970-08-17). "Death following self-poisoning with aspirin". Journal of the American Medical Association. PMID 5468267. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)

[FL_Kaufman-54] Kaufman, FL (1970-04). "Darvon poisoning with delayed salicylism: a case report". Pediatrics. 49 (4): 610–1. PMID 5013423. {{cite journal}}: Check date values in: |date= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)

[G_Levy-55] Levy, G (1972-09-31). "Salicylate accumulation kinetics in man". New England Journal of Medicine. 287 (9): 430–2. PMID 5044917. {{cite journal}}: Check date values in: |date= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)

[O_Hartwig-56] Hartwig, Otto H (1983-11-14). "Pharmacokinetic considerations of common analgesics and antipyretics". American Journal of Medicine. 75 (5A): 30–7. doi:10.1016/0002-9343(83)90230-9. PMC 1725844. PMID 6606362. {{cite journal}}: Cite has empty unknown parameter: |coauthors= (help)

[AK_Done-57] Done, AK (1960-11). "Salicylate intoxication. Significance of measurements of salicylate in blood in cases of acute ingestion". Pediatrics: 800–7. PMID 13723722. {{cite journal}}: Check date values in: |date= (help); Cite has empty unknown parameter: |coauthors= (help)

[Chyka2007-58] Chyka PA, Erdman AR, Christianson G, Wax PM, Booze LL, Manoguerra AS, Caravati EM, Nelson LS, Olson KR, Cobaugh DJ, Scharman EJ, Woolf AD, Troutman WG; Americal Association of Poison Control Centers; Healthcare Systems Bureau, Health Resources and Services Administration, Department of Health and Human Services. (2007). "Salicylate poisoning: an evidence-based consensus guideline for out-of-hospital management". Clin Toxicol (Phila). 45 (2): 95–131. doi:10.1080/15563650600907140. PMID 17364628.{{cite journal}}: CS1 maint: multiple names: authors list (link)

[59] Prescott LF, Balali-Mood M, Critchley JA, Johnstone AF, Proudfoot AT (1982). "Diuresis or urinary alkalinisation for salicylate poisoning?". Br Med J (Clin Res Ed). 285 (6352): 1383–6. PMC 1500395. PMID 6291695. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)

[EmergMed2002-Dargan-60] Dargan PI, Wallace CI, Jones AL. (2002). "An evidenced based flowchart to guide the management of acute salicylate (aspirin) overdose". Emerg Med J. 19 (3): 206–9. doi:10.1136/emj.19.3.206. PMC 1725844. PMID 11971828.{{cite journal}}: CS1 maint: multiple names: authors list (link)

[drugs.com-61] "Aspirin information from Drugs.com". Drugs.com. Retrieved 2008-05-08.

[personalmd-62] "Oral Aspirin information". First DataBank. Retrieved 2008-05-08.

[pmid16247191-63] Raithel M, Baenkler HW, Naegel A; et al. (2005). "Significance of salicylate intolerance in diseases of the lower gastrointestinal tract" (PDF). J. Physiol. Pharmacol. 56 Suppl 5: 89–102. PMID 16247191. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)

[pmid8566739-64] Senna GE, Andri G, Dama AR, Mezzelani P, Andri L (1995). "Tolerability of imidazole salycilate in aspirin-sensitive patients". Allergy Proc. 16 (5): 251–4. PMID 8566739.{{cite journal}}: CS1 maint: multiple names: authors list (link)

[mercksource-65] PDR® Guide to Over the Counter (OTC) Drugs, retrieved 2008-04-28.

[66] G6PD (Glucose-6-Phosphate Dehydrogenase) Deficiency, University of Virginia, retrieved 2008-05-07

[67] G6PD (Glucose-6-Phosphate Dehydrogenase) Deficiency, University of Texas Medical Branch, retrieved 2008-05-07

[68] Dengue and Dengue Hemorrhagic Fever: Information for Health Care Practitioners, retrieved 2008-04-28

[69] "Aspirin may be less effective heart treatment for women than men". University of Michigan. 2007-04-26. Retrieved 2007-09-09. {{cite news}}: Check date values in: |date= (help)

[70] Dorsch MP, Lee JS, Lynch DR, Dunn SP, Rodgers JE, Schwartz T, Colby E, Montague D, Smyth SS (2007). "Aspirin Resistance in Patients with Stable Coronary Artery Disease with and without a History of Myocardial Infarction". Ann Pharmacother. 41 (May): 737. doi:10.1345/aph.1H621. PMID 17456544. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)

[71] "Increased risk of heart attack or stroke for patients who are resistant to aspirin". 2008-01-17. Retrieved 2008-01-20.

[H_Toft-72] Sørensen HT, Mellemkjaer L, Blot WJ; et al. (2000). "Risk of upper gastrointestinal bleeding associated with use of low-dose aspirin". Am. J. Gastroenterol. 95 (9): 2218–24. doi:10.1111/j.1572-0241.2000.02248.x. PMID 11007221. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)

[73] Delaney JA, Opatrny L, Brophy JM & Suissa S (2007). "Drug drug interactions between antithrombotic medications and the risk of gastrointestinal bleeding". CMAJ. 177 (4): 347–51. doi:10.1503/cmaj.070186. PMC 1942107. PMID 17698822. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)

[Gutton-74] Guitton MJ, Caston J, Ruel J, Johnson RM, Pujol R, Puel JL (2003). "Salicylate induces tinnitus through activation of cochlear NMDA receptors". J. Neurosci. 23 (9): 3944–52. PMID 12736364. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)

[75] Rogers MF, Schonberger LB, Hurwitz ES & Rowley DL (1985). "National Reye syndrome surveillance, 1982". Pediatrics. 75 (2): 260–4. PMID 3969325. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)

[76] Rogan WJ, Yang GC & Kimbrough RD (1985). "Aflatoxin and Reye's syndrome: a study of livers from deceased cases". ArchEnviron Health. 40 (2): 91–5. PMID 4004347. {{cite journal}}: Unknown parameter |month= ignored (help)

[77] Scher, K.S. (1996). "Unplanned reoperation for bleeding". Am Surg. 62 (1): 52–55. PMID 8540646. {{cite journal}}: Unknown parameter |month= ignored (help)

[78] Berges-Gimeno MP & Stevenson DD (2004). "Nonsteroidal anti-inflammatory drug-induced reactions and desensitization". J Asthma. 41 (4): 375–84. doi:10.1081/JAS-120037650. PMID 15281324. {{cite journal}}: Unknown parameter |month= ignored (help)

[interactions-79] Katzung (1998), p. 584.

[80] Loh HS, Watters K & Wilson CW (1973). "The Effects of Aspirin on the Metabolic Availability of Ascorbic Acid in Human Beings". J Clin Pharmacol. 13 (11): 480–6. PMID 4490672.

[81] Basu TK (1982). "Vitamin C-aspirin interactions". Int J Vitam Nutr Res Suppl. 23: 83–90. PMID 6811490. {{cite journal}}: Cite has empty unknown parameter: |month= (help)

[82] Ioannides C, Stone AN, Breacker PJ & Basu TK (1982). "Impairment of absorption of ascorbic acid following ingestion of aspirin in guinea pigs". Biochem Pharmacol. 31 (24): 4035–8. doi:10.1016/0006-2952(82)90652-9. PMID 6818974. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)

[BNF-83] British National Formulary (45 ed.). British Medical Journal and Royal Pharmaceutical Society of Great Britain. 2003. {{cite book}}: Unknown parameter |month= ignored (help)

[84] Aspirin monograph: dosages, etc

[85] British National Formulary for Children. British Medical Journal and Royal Pharmaceutical Society of Great Britain. 2006.

[Pediatrics1982-gaudreault-86] Gaudreault P, Temple AR, Lovejoy FH Jr. (1982). "The relative severity of acute versus chronic salicylate poisoning in children: a clinical comparison". Pediatrics. 70 (4): 566–9. PMID 7122154.{{cite journal}}: CS1 maint: multiple names: authors list (link)

[ActaAnaesthesiol1987-Thisted-87] Thisted B, Krantz T, Stroom J, Sorensen MB. (1987). "Acute salicylate self-poisoning in 177 consecutive patients treated in ICU". Acta Anaesthesiol Scand. 31 (4): 312–6. PMID 3591255.{{cite journal}}: CS1 maint: multiple names: authors list (link)

[ArchInternMed1981-Temple-88] Temple AR. (1981). "Acute and chronic effects of aspirin toxicity and their treatment". Arch Intern Med. 141 (3 Spec No): 364–9. doi:10.1001/archinte.141.3.364. PMID 7469627.

[”jtoxclintox2004-vale”-89] Vale JA, Kulig K; American Academy of Clinical Toxicology; European Association of Poisons Centres and Clinical Toxicologists. (2004). "Position paper: gastric lavage". J Toxicol Clin Toxicol. 42 (7): 933–43. doi:10.1081/CLT-200045006. PMID 15641639.{{cite journal}}: CS1 maint: multiple names: authors list (link)

[BMJ1985-hillman-90] Hillman RJ, Prescott LF. (1985). "Treatment of salicylate poisoning with repeated oral charcoal". Br Med J (Clin Res Ed). 291 (6507): 1472. PMID 3933714.

[ArchInternMed1990-Kirshenbaum-91] Kirshenbaum LA, Mathews SC, Sitar DS, Tenenbein M. (1990). "Does multiple-dose charcoal therapy enhance salicylate excretion?". Arch Intern Med. 150 (6): 1281–3. doi:10.1001/archinte.150.6.1281. PMID 2191636.{{cite journal}}: CS1 maint: multiple names: authors list (link)

[drugs1986-Meredith-92] Meredith TJ, Vale JA. (1986). "Non-narcotic analgesics. Problems of overdosage". Drugs. 32 (Suppl 4): 117–205. doi:10.2165/00003495-198600324-00013. PMID 3552583.

[AmJEmergMed2001-Litovitz-93] Litovitz TL, Klein-Schwartz W, White S, Cobaugh DJ, Youniss J, Omslaer JC, Drab A, Benson BE (2001). "2000 Annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System". Am J Emerg Med. 19 (5): 337–95. doi:10.1053/ajem.2001.25272. PMID 11555795.{{cite journal}}: CS1 maint: multiple names: authors list (link)

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]

[9]

[10]

[11]

[12]

[13]

[14]

[15]

[16]

[17]

[18]

[19]

[20]

[21]

[22]

[23]

[24]

[25]

[26]

[27]

[28]

[29]

[30]

[31]

[32]

[33]

[34]

[35]

[36]

[37]

[38]

[39]

[40]

[41]

[42]

[43]

[44]

[45]

[46]

[47]

[48]

[49]

[50]

[51]

[52]

[53]

[54]

[55]

[56]

[57]

[58]

[59]

[60]

[61]

[62]

[63]

[64]

[65]

[66]

[67]

[68]

[69]

[70]

[71]

[72]

[73]

[74]

[75]

[76]

[77]

[78]

[79]

[80]

[81]

[82]

[83]

[84]

[85]

[86]

[87]

[88]

[89]

[90]

[91]

[92]

[93]

v t e Non-steroidal anti-inflammatory drugs (NSAIDs) (primarily M01A and M02A, also N02BA)
pyrazolones / pyrazolidines	Aminophenazone Ampyrone Azapropazone Clofezone Difenamizole Famprofazone Feprazone Kebuzone Metamizole Mofebutazone Morazone Nifenazone Oxyphenbutazone Phenazone Phenylbutazone Propyphenazone Sulfinpyrazone Suxibuzone^‡
salicylates	Aspirin (acetylsalicylic acid)^# Aloxiprin Benorylate Carbasalate calcium Diflunisal Dipyrocetyl Ethenzamide Guacetisal Magnesium salicylate Methyl salicylate Salsalate Salicin Salicylamide Salicylic acid (salicylate) Sodium salicylate
acetic acid derivatives and related substances	Aceclofenac Acemetacin Alclofenac Amfenac Bendazac Bromfenac Bufexamac Bumadizone Diclofenac Difenpiramide Etodolac Felbinac Fenclozic acid Fentiazac Indometacin Indometacin farnesil Isoxepac Ketorolac Lonazolac Mofezolac Oxametacin Prodolic acid Proglumetacin Sulindac Tiopinac Tolmetin Zomepirac^†
oxicams	Ampiroxicam Droxicam Isoxicam Lornoxicam Meloxicam Piroxicam Pivoxicam Tenoxicam
propionic acid derivatives (profens)	Alminoprofen Benoxaprofen^† Carprofen^‡ Dexibuprofen Dexketoprofen Fenbufen Fenoprofen Flunoxaprofen Flurbiprofen Ibuprofen^# Ibuproxam Indoprofen^† Ketoprofen Loxoprofen Miroprofen Naproxen Oxaprozin Pelubiprofen Piketoprofen Pirprofen Suprofen Tarenflurbil Tepoxalin^‡ Tiaprofenic acid Vedaprofen^‡ Zaltoprofen COX-inhibiting nitric oxide donator: Naproxcinod
n-arylanthranilic acids (fenamates)	Azapropazone Clonixin Etofenamate Floctafenine Flufenamic acid Flunixin Flutiazin Glafenine^† Meclofenamic acid Mefenamic acid Morniflumate Niflumic acid Tolfenamic acid
COX-2 inhibitors (coxibs)	Apricoxib Celecoxib (+tramadol) Cimicoxib^‡ Deracoxib^‡ Etoricoxib Firocoxib^‡ Lumiracoxib^† Mavacoxib^‡ Parecoxib Robenacoxib^‡ Rofecoxib^† Valdecoxib^†
other	Aminopropionitrile Benzydamine Chondroitin sulfate Diacerein Fluproquazone Glucosamine Glycosaminoglycan Hyperforin Nabumetone Nimesulide Oxaceprol Proquazone Superoxide dismutase / orgotein Tenidap
NSAID combinations	Ibuprofen/famotidine Ibuprofen/hydrocodone Ibuprofen/oxycodone Ibuprofen/paracetamol Meloxicam/bupivacaine Naproxen/diphenhydramine Naproxen/esomeprazole
Key: underline indicates initially developed first-in-class compound of specific group; ^#WHO-Essential Medicines; ^†withdrawn drugs; ^‡veterinary use.
category commons portal

v t e Non-steroidal anti-inflammatory drugs (NSAIDs) (primarily M01A and M02A, also N02BA)
pyrazolones / pyrazolidines	Aminophenazone Ampyrone Azapropazone Clofezone Difenamizole Famprofazone Feprazone Kebuzone Metamizole Mofebutazone Morazone Nifenazone Oxyphenbutazone Phenazone Phenylbutazone Propyphenazone Sulfinpyrazone Suxibuzone^‡
salicylates	Aspirin (acetylsalicylic acid)^# Aloxiprin Benorylate Carbasalate calcium Diflunisal Dipyrocetyl Ethenzamide Guacetisal Magnesium salicylate Methyl salicylate Salsalate Salicin Salicylamide Salicylic acid (salicylate) Sodium salicylate
acetic acid derivatives and related substances	Aceclofenac Acemetacin Alclofenac Amfenac Bendazac Bromfenac Bufexamac Bumadizone Diclofenac Difenpiramide Etodolac Felbinac Fenclozic acid Fentiazac Indometacin Indometacin farnesil Isoxepac Ketorolac Lonazolac Mofezolac Oxametacin Prodolic acid Proglumetacin Sulindac Tiopinac Tolmetin Zomepirac^†
oxicams	Ampiroxicam Droxicam Isoxicam Lornoxicam Meloxicam Piroxicam Pivoxicam Tenoxicam
propionic acid derivatives (profens)	Alminoprofen Benoxaprofen^† Carprofen^‡ Dexibuprofen Dexketoprofen Fenbufen Fenoprofen Flunoxaprofen Flurbiprofen Ibuprofen^# Ibuproxam Indoprofen^† Ketoprofen Loxoprofen Miroprofen Naproxen Oxaprozin Pelubiprofen Piketoprofen Pirprofen Suprofen Tarenflurbil Tepoxalin^‡ Tiaprofenic acid Vedaprofen^‡ Zaltoprofen COX-inhibiting nitric oxide donator: Naproxcinod
n-arylanthranilic acids (fenamates)	Azapropazone Clonixin Etofenamate Floctafenine Flufenamic acid Flunixin Flutiazin Glafenine^† Meclofenamic acid Mefenamic acid Morniflumate Niflumic acid Tolfenamic acid
COX-2 inhibitors (coxibs)	Apricoxib Celecoxib (+tramadol) Cimicoxib^‡ Deracoxib^‡ Etoricoxib Firocoxib^‡ Lumiracoxib^† Mavacoxib^‡ Parecoxib Robenacoxib^‡ Rofecoxib^† Valdecoxib^†
other	Aminopropionitrile Benzydamine Chondroitin sulfate Diacerein Fluproquazone Glucosamine Glycosaminoglycan Hyperforin Nabumetone Nimesulide Oxaceprol Proquazone Superoxide dismutase / orgotein Tenidap
NSAID combinations	Ibuprofen/famotidine Ibuprofen/hydrocodone Ibuprofen/oxycodone Ibuprofen/paracetamol Meloxicam/bupivacaine Naproxen/diphenhydramine Naproxen/esomeprazole
Key: underline indicates initially developed first-in-class compound of specific group; ^#WHO-Essential Medicines; ^†withdrawn drugs; ^‡veterinary use.
category commons portal