text:
- the acetylated derivative of salicylic acid; used as an analgesic anti-inflammatory drug (trade names Bayer, Empirin, and St. Joseph) usually taken in tablet form; used as an antipyretic; slows clotting of the blood by poisoning platelets (同)acetylsalicylic_acid, Bayer, Empirin, St. Joseph
- aspirin coated with a substance capable of neutralizing acid (trade name Bufferin) (同)Bufferin
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出典(authority):フリー百科事典『ウィキペディア(Wikipedia)』「2015/04/06 23:22:19」(JST)
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|Systematic (IUPAC) name
|2-(acetoxy)benzoic acid
|Clinical data
Legal status
Routes of
|Most commonly oral, also rectal, lysine acetylsalicylate may be given intravenously or intramuscularly
|Pharmacokinetic data
|Protein binding
|Hepatic, (CYP2C19 and possibly CYP3A), some is also hydrolysed to salicylate in the gut wall.[2]
|Dose-dependent; 2–3 hours for low doses, 15–30 hours for large doses.[2]
|Urine (80–100%), sweat, saliva, feces[1]
CAS Registry Number
ATC code
|2-acetoxybenzoic acid
|PDB ligand ID
|AIN (PDBe, RCSB PDB)
|Chemical data
Molecular mass
|180.157 g/mol
|Physical data
|1.40 g/cm3
|Melting point
|Boiling point
|140 °C (284 °F) (decomposes)
Solubility in water
|3 mg/mL (20 °C)
|Y (what is this?) (verify)
Aspirin (BAN, USAN), also known as acetylsalicylic acid (/əˌsiːtəlˌsælɨˈsɪlɨk/ ə-SEE-təl-SAL-i-SIL-ik) [ASA], 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.[2] Aspirin also has an antiplatelet effect by inhibiting the production of thromboxane, which under normal circumstances binds platelet molecules together to create a patch over damaged walls of blood vessels. Because the platelet patch can become too large and also block blood flow, locally and downstream, aspirin is also used long-term, at low doses, to help prevent heart attacks, strokes, and blood clot formation in people at high risk of developing blood clots.[3] Also, 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.[4][5] Aspirin may be effective at preventing certain types of cancer, particularly colorectal cancer.[6][7][8]
The main side effects of aspirin are gastrointestinal ulcers, stomach bleeding, and ringing in the ears, especially with higher doses. In children and adolescents, aspirin is not recommended for flu-like symptoms or viral illnesses, because of the risk of Reye's syndrome.[9]
Aspirin is part of a group of medications called nonsteroidal anti-inflammatory drugs (NSAIDs), but differs from most other NSAIDs in the mechanism of action. Though it and others with similar structure, called the salicylates, have similar effects (antipyretic, anti-inflammatory, analgesic) to the other NSAIDs and inhibit the same enzyme cyclooxygenase (COX), aspirin does so in an irreversible manner and, unlike others, affects more the COX-1 variant than the COX-2 variant of the enzyme.[10]
The active ingredient of aspirin was first discovered from the bark of the willow tree in 1763 by Edward Stone of Wadham College, University of Oxford. He had discovered salicylic acid, the active ingredient of aspirin.[11] Aspirin was first synthesized by Felix Hoffmann, a chemist with the German company Bayer in 1897.[12][13] Aspirin is one of the most widely used medications in the world, with an estimated 40,000 tonnes of it being consumed each year.[14] In countries where "Aspirin" is a registered trademark owned by Bayer, the generic term is acetylsalicylic acid (ASA).[15] It is on the WHO Model List of Essential Medicines, the most important medications needed in a basic health system.[16]
- 1 Medical use
- 1.1 Pain
- 1.1.1 Headache
- 1.2 Fever
- 1.3 Swelling and inflammation
- 1.4 Heart attacks and strokes
- 1.5 After surgery
- 1.6 Cancer prevention
- 1.7 Other uses
- 1.8 Resistance
- 1.9 Dosage
- 1.1 Pain
- 2 Adverse effects
- 2.1 Contraindications
- 2.2 Gastrointestinal
- 2.3 Central effects
- 2.4 Reye's syndrome
- 2.5 Hives and swelling
- 2.6 Other adverse effects
- 2.7 Overdose
- 2.8 Interactions
- 3 Chemical properties
- 4 Physical properties
- 4.1 Synthesis
- 4.2 Polymorphism
- 5 Mechanism of action
- 5.1 Discovery of the mechanism
- 5.2 Suppression of prostaglandins and thromboxanes
- 5.3 COX-1 and COX-2 inhibition
- 5.4 Additional mechanisms
- 5.5 Hypothalamic-pituitary-adrenal activity
- 6 Pharmacokinetics
- 7 History
- 7.1 Trademark
- 8 Compendial status
- 9 Veterinary use
- 10 References
- 10.1 Further reading
- 11 External links
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 disease.[17] Lower doses of aspirin have also shown to reduce the risk of death from a heart attack, or the risk of stroke in some circumstances.[18][19][20] There is some evidence that aspirin is effective at preventing colorectal cancer, though the mechanisms of this effect are unclear.[21]
Aspirin is an effective analgesic for acute pain, but is generally considered inferior to ibuprofen for the alleviation of pain because aspirin is more likely to cause gastrointestinal bleeding.[22] Aspirin is generally ineffective for those pains caused by muscle cramps, bloating, gastric distension, or acute skin irritation.[23] As with other NSAIDs, combinations of aspirin and caffeine provide slightly greater pain relief than aspirin alone.[24] Effervescent formulations of aspirin, such as Alka-Seltzer or Blowfish,[25] relieve pain faster than aspirin in tablets,[26] which makes them useful for the treatment of migraines.[27]
Topical aspirin may be effective for treating some types of neuropathic pain.[28]
Aspirin, either by itself or in a combined formulation, effectively treats some types of headache, but its efficacy may be questionable for others. Secondary headaches, meaning those caused by another disorder or trauma, should be promptly treated by a medical provider.
Among primary headaches, the International Classification of Headache Disorders distinguishes between tension headache (the most common), migraine, and cluster headache. Aspirin or other over-the-counter analgesics are widely recognized as effective for the treatment of tension headache.[29] Aspirin, especially as a component of an acetaminophen/aspirin/caffeine formulation, e.g., Excedrin Migraine, is considered a first-line therapy in the treatment of migraine, and comparable to lower doses of sumatriptan. It is most effective at stopping migraines when they are first beginning.[30]
Like its ability to control pain, aspirin's ability to control fever is due to its action on the prostaglandin system through its irreversible inhibition of COX.[31] Although aspirin's use as an antipyretic in adults is well-established, many medical societies and regulatory agencies (including the American Academy of Family Physicians, the American Academy of Pediatrics, and the U.S. Food and Drug Administration (FDA) strongly advise against using aspirin for treatment of fever in children because of the risk of Reye's syndrome, a rare but often fatal illness associated with the use of aspirin or other salicylates in children during episodes of viral or bacterial infection.[32][33][34] Because of the risk of Reye's syndrome in children, in 1986, the FDA required labeling on all aspirin-containing medications advising against its use in children and teenagers.[35]
Swelling and inflammation
Aspirin is used as an anti-inflammatory agent for both acute and long-term inflammation,[36] as well as for treatment of inflammatory diseases, such as rheumatoid arthritis.[17]
Heart attacks and strokes
The first studies of the effect of aspirin on cardiac function and stroke prevention was carried out by Professor Peter Sleight,[37] Emeritus Professor of Cardiovascular Medicine at Oxford University in the early 1970s.[38] Sleight and his research team at Oxford led the way and formed the foundation for the research into the use of aspirin in the prevention of other medical conditions.
For a subset of the population, aspirin may help prevent heart attacks and strokes. In lower doses, aspirin has been known to prevent the progression of existing cardiovascular disease, and reduce the frequency of these events for those with a history of them.[39][40] (This is known as secondary prevention.)
Aspirin appears to offer little benefit to those at lower risk of heart attack or stroke—for instance, those without a history of these events or with pre-existing disease. Some studies recommend aspirin on a case-by-case basis,[41][42] while others have suggested the risks of other events, such as gastrointestinal bleeding, were significant enough to outweigh any potential benefit, and recommended against using aspirin for primary prevention entirely.[43]
Complicating the use of aspirin for prevention is the phenomenon of aspirin resistance.[44][45] For patients who are resistant, aspirin's efficacy is reduced, which can cause an increased risk of stroke.[46] Some authors have suggested testing regimens to identify those patients who are resistant to aspirin or other antithrombotic drugs (such as clopidogrel).[47]
Aspirin has also been suggested as a component of a polypill[48][49] for prevention of cardiovascular disease.
After surgery
After percutaneous coronary interventions (PCIs), such as the placement of a coronary artery stent, a U.S. Agency for Healthcare Research and Quality guideline recommends that aspirin be taken indefinitely.[50] Frequently, 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). United States and European Union guidelines disagree somewhat about how long, and for what indications this combined therapy should be continued after surgery. U.S. guidelines recommend DAPT for at least 12 months, while EU guidelines recommend DAPT for 6–12 months after a drug-eluting stent placement.[51] However, they agree that aspirin be continued indefinitely after DAPT is complete.
Cancer prevention
Aspirin reduces the overall risk of both getting cancer and dying from cancer.[52] This effect is particularly beneficial for colorectal cancer (CRC).[21][53][54][55]
Some conclude the benefits are greater than the risks due to bleeding in those at average risk.[52] Other are unclear if the benefits are greater than the risk.[56][57] Given this uncertainty, the 2007 United States Preventive Services Task Force guidelines on this topic recommended against the use of aspirin for prevention of CRC in people with average risk.[58]
Other uses
Aspirin is a first-line treatment for the fever and joint-pain symptoms of acute rheumatic fever. The therapy often lasts for one to two weeks, and is rarely indicated for longer periods. After fever and pain have subsided, the aspirin is no longer necessary, since it does not decrease the incidence of heart complications and residual rheumatic heart disease.[59][60] Naproxen has been shown to be as effective as aspirin and less toxic, but due to the limited clinical experience, naproxen is recommended only as a second-line treatment.[59][61]
Along with rheumatic fever, Kawasaki disease remains one of the few indications for aspirin use in children[62] in spite of a lack of high quality evidence for its effectiveness.[63]
Low-dose aspirin supplementation has moderate benefits when used for prevention of pre-eclampsia.[64][65]
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 women are more likely to be resistant than men,[66] and a different, aggregate study of 2,930 patients found 28% were resistant.[67] A study in 100 Italian patients, though, found, of the apparent 31% aspirin-resistant subjects, only 5% were truly resistant, and the others were noncompliant.[68] Another study of 400 healthy volunteers found no subjects who were truly resistant, but some had "pseudoresistance, reflecting delayed and reduced drug absorption".[69]
Adult aspirin tablets are produced in standardised sizes, which vary slightly from country to country, for example 300 mg in Britain and 325 mg (or 5 grains) in the United States. Smaller doses are based on these standards, e.g., 75-mg and 81-mg tablets. The 81-mg (11⁄4-grain) tablets are called "baby-strength", though they are not intended to be administered to infants and children. No medical significance occurs due to the slight difference in dosage between the 75-mg and the 81-mg tablets. Of historic interest, in the United States, a 325-mg dose is equivalent to the historic 5-grain aspirin tablet in use prior to the metric system.[citation needed]
In general, for adults, doses are taken four times a day for fever or arthritis,[70] with doses near the maximal daily dose used historically for the treatment of rheumatic fever.[71] For the prevention of myocardial infarction (MI) in someone with documented or suspected coronary artery disease, much lower doses are taken once daily.[70]
Recommendations from the USPSTF[72] on the use of aspirin for the primary prevention of coronary heart disease encourage men aged 45–79 and women aged 55–79 to use aspirin when the potential benefit of a reduction in MI for men or stroke for women outweighs the potential harm of an increase in gastrointestinal hemorrhage.[73] The WHI study said regular low-dose (75- or 81-mg) aspirin female users had a 25% lower risk of death from cardiovascular disease and a 14% lower risk of death from any cause.[73] Low-dose aspirin use was also associated with a trend toward lower risk of cardiovascular events, and lower aspirin doses (75 or 81 mg/day) may optimize efficacy and safety for patients requiring aspirin for long-term prevention.[73]
In children with Kawasaki disease, aspirin is 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.[74]
Adverse effects
Aspirin should not be taken by people who are allergic to ibuprofen or naproxen,[75][76] or who have salicylate intolerance[77][78] or a more generalized drug intolerance to NSAIDs, and caution should be exercised in those with asthma or NSAID-precipitated bronchospasm. Owing to its effect on the stomach lining, manufacturers recommend people with peptic ulcers, mild diabetes, or gastritis seek medical advice before using aspirin.[75][79] Even if none of these conditions is present, the risk of stomach bleeding is still increased when aspirin is taken with alcohol or warfarin.[75][76] Patients with hemophilia or other bleeding tendencies should not take aspirin or other salicylates.[75][79] Aspirin is known to cause hemolytic anemia in people who have the genetic disease glucose-6-phosphate dehydrogenase deficiency, particularly in large doses and depending on the severity of the disease.[80] Use of aspirin during dengue fever is not recommended owing to increased bleeding tendency.[81] People with kidney disease, hyperuricemia, or gout should not take aspirin because it inhibits the kidneys' ability to excrete uric acid, thus may exacerbate these conditions. Aspirin should not be given to children or adolescents to control cold or influenza symptoms, as this has been linked with Reye's syndrome.[9]
Aspirin use has been shown to increase the risk of gastrointestinal bleeding.[82] 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.[82] Combining aspirin with other NSAIDs has also been shown to further increase this risk.[82] Using aspirin in combination with clopidogrel or warfarin also increases the risk of upper gastrointestinal bleeding.[83]
Blockade of COX-1 by aspirin apparently results in the upregulation of COX-2 as part of a gastric defense[84] and that taking COX-2 inhibitors concurrently with aspirin increases the gastric mucosal erosion.[85] Therefore, caution should be exercised if combining aspirin with any "natural" supplements with COX-2-inhibiting properties, such as garlic extracts, curcumin, bilberry, pine bark, ginkgo, fish oil, resveratrol, genistein, quercetin, resorcinol, and others.
In addition to enteric coating, "buffering" is the other main method companies have used to try to mitigate the problem of gastrointestinal bleeding. Buffering agents are intended to work by preventing the aspirin from concentrating in the walls of the stomach, although the benefits of buffered aspirin are disputed. Almost any buffering agent used in antacids can be used; Bufferin, for example, uses magnesium oxide. Other preparations use calcium carbonate.[86]
Taking it with vitamin C is a more recently investigated method of protecting the stomach lining. Taking equal doses of vitamin C and aspirin may decrease the amount of stomach damage that occurs compared to taking aspirin alone.[87][88]
Central effects
Large doses of salicylate, a metabolite of aspirin, cause temporary tinnitus (ringing in the ears) based on experiments in rats, via the action on arachidonic acid and NMDA receptors cascade.[89]
Reye's syndrome
Reye's syndrome, a rare but severe illness characterized by acute encephalopathy and fatty liver, can occur when children or adolescents are given aspirin for a fever or other illnesses or infections. From 1981 through 1997, 1207 cases of Reye's syndrome in under-18 patients were reported to the U.S. Centers for Disease Control and Prevention. Of these, 93% reported being ill in the three weeks preceding onset of Reye's syndrome, most commonly with a respiratory infection, chickenpox, or diarrhea. Salicylates were detectable in 81.9% of children for whom test results were reported.[90] After the association between Reye's syndrome and aspirin was reported, and safety measures to prevent it (including a Surgeon General's warning, and changes to the labeling of aspirin-containing drugs) were implemented, aspirin taken by children declined considerably in the United States, as did the number of reported cases of Reye's syndrome; a similar decline was found in the United Kingdom after warnings against pediatric aspirin use were issued.[90] The U.S. Food and Drug Administration now recommends aspirin (or aspirin-containing products) should not be given to anyone under the age of 12 who has a fever,[9] and the British Medicines and Healthcare products Regulatory Agency recommends children who are under 16 years of age should not take aspirin, unless it is on the advice of a doctor.[91]
Hives and swelling
For a small number of people, taking aspirin can result in symptoms resembling an allergic reaction, including hives, swelling, and headache. The reaction is caused by salicylate intolerance and is not a true allergy, but rather an inability to metabolize even small amounts of aspirin, resulting in an overdose.
Other adverse effects
Aspirin can induce swelling of skin tissues in some people. In one study, angioedema appeared one to six hours after ingesting aspirin in some of the patients. However, when the aspirin was taken alone, it did not cause angioedema in these patients; the aspirin had been taken in combination with another NSAID-induced drug when angioedema appeared.[92]
Aspirin causes an increased risk of cerebral microbleeds having the appearance on MRI scans of 5 to 10 mm or smaller, hypointense (dark holes) patches.[93][94] Such cerebral microbleeds are important, since they often occur prior to ischemic stroke or intracerebral hemorrhage, Binswanger disease, and Alzheimer's disease.[original research?]
A study of a group with a mean dosage of aspirin of 270 mg per day estimated an average absolute risk increase in intracerebral hemorrhage (ICH) of 12 events per 10,000 persons.[95] In comparison, the estimated absolute risk reduction in myocardial infarction was 137 events per 10,000 persons, and a reduction of 39 events per 10,000 persons in ischemic stroke.[95] In cases where ICH already has occurred, aspirin use results in higher mortality, with a dose of about 250 mg per day resulting in a relative risk of death within three months after the ICH around 2.5 (95% confidence interval 1.3 to 4.6).[96]
Aspirin and other NSAIDs can cause hyperkalemia by inducing a hyporenin hypoaldosteronic state via inhibition of prostaglandin synthesis; however, these agents do not typically cause hyperkalemia by themselves in the setting of normal renal function and euvolemic state.[97]
Aspirin can cause prolonged bleeding after operations for up to 10 days. In one study, 30 of 6499 elective surgical patients required reoperations to control bleeding. Twenty had diffuse bleeding and 10 had bleeding from a site. Diffuse, but not discrete, bleeding was associated with the preoperative use of aspirin alone or in combination with other NSAIDS in 19 of the 20 diffuse bleeding patients.[98]
|Prothrombin time
|Partial thromboplastin time
|Bleeding time
|Platelet count
|Vitamin K deficiency or warfarin
|Normal or mildly prolonged
|Disseminated intravascular coagulation
|Von Willebrand disease
|Prolonged or unaffected
|Liver failure, early
|Liver failure, end-stage
|Congenital afibrinogenemia
|Factor V deficiency
|Factor X deficiency as seen in amyloid purpura
|Glanzmann's thrombasthenia
|Bernard-Soulier syndrome
|Decreased or unaffected
|Factor XII deficiency
|C1INH deficiency
Aspirin overdose can be acute or chronic. In acute poisoning, a single large dose is taken; in chronic poisoning, higher than normal 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%;[99] chronic overdose may be especially severe in children.[100] Toxicity is managed with a number of potential treatments, including activated charcoal, intravenous dextrose and normal saline, sodium bicarbonate, and dialysis.[101] The diagnosis of poisoning usually involves measurement of plasma salicylate, the active metabolite of aspirin, by automated spectrophotometric methods. Plasma salicylate levels in general range from 30–100 mg/l after usual therapeutic doses, 50–300 mg/l in patients taking high doses and 700–1400 mg/l following acute overdose. Salicylate is also produced as a result of exposure to bismuth subsalicylate, methyl salicylate, and sodium salicylate.[102][103]
Aspirin is known to interact with other drugs. For example, acetazolamide and ammonium chloride are known to enhance the intoxicating effect of salicylates, and alcohol also increases the gastrointestinal bleeding associated with these types of drugs.[75][76] Aspirin is known to displace a number of drugs from protein-binding sites in the blood, including the antidiabetic drugs tolbutamide and chlorpropamide, warfarin, methotrexate, phenytoin, probenecid, valproic acid (as well as interfering with beta oxidation, an important part of valproate metabolism), and other NSAIDs. Corticosteroids may also reduce the concentration of aspirin. Ibuprofen can negate the antiplatelet effect of aspirin used for cardioprotection and stroke prevention.[104] The pharmacological activity of spironolactone may be reduced by taking aspirin, and it is known to compete with penicillin G for renal tubular secretion.[105] Aspirin may also inhibit the absorption of vitamin C.[106][107][108]
Chemical properties
Aspirin decomposes rapidly in solutions of ammonium acetate or of the acetates, carbonates, citrates, or hydroxides of the alkali metals. It 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.[109]
Physical properties
Aspirin, an acetyl derivative of salicylic acid, is a white, crystalline, weakly acidic substance, with a melting point of 136 °C (277 °F), and a boiling point of 140 °C (284 °F).[110] Its acid dissociation constant (pKa) is 3.5 at 25 °C (77 °F).[111]
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 turns salicylic acid's hydroxyl group into an ester group (R-OH → R-OCOCH3). This process yields aspirin and acetic acid, which is considered a byproduct of this reaction. Small amounts of sulfuric acid (and occasionally phosphoric acid) are almost always used as a catalyst. This method is commonly employed in undergraduate teaching labs.[112]
- Reaction mechanism
Formulations containing high concentrations of aspirin often smell like vinegar[113] because aspirin can decompose through hydrolysis in moist conditions, yielding salicylic and acetic acids.[114]
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. That aspirin might have a second crystalline form was suspected since the 1960s. The elusive second polymorph was first discovered by Vishweshwar and coworkers in 2005,[115] and fine structural details were given by Bond et al.[116] A new crystal type was found after attempted cocrystallization of aspirin and levetiracetam from hot acetonitrile. The form II is only stable at 100 K and reverts 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.
Mechanism of action
Discovery of the mechanism
In 1971, British pharmacologist John Robert Vane, then employed by the Royal College of Surgeons in London, showed aspirin suppressed the production of prostaglandins and thromboxanes.[117][118] For this discovery he was awarded the 1982 Nobel Prize in Physiology or Medicine, jointly with Sune K. Bergström and Bengt I. Samuelsson.[119] In 1984, he was made a Knight Bachelor.
Suppression of prostaglandins and thromboxanes
Aspirin's ability to suppress the production of prostaglandins and thromboxanes is due to its irreversible inactivation of the cyclooxygenase (COX; officially known as prostaglandin-endoperoxide synthase, PTGS) enzyme 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 PTGS enzyme. This makes aspirin different from other NSAIDs (such as diclofenac and ibuprofen), which are reversible inhibitors.
Low-dose aspirin use irreversibly blocks the formation of thromboxane A2 in platelets, producing an inhibitory effect on platelet aggregation during the lifetime of the affected platelet (8–9 days). This antithrombotic property makes aspirin useful for reducing the incidence of heart attacks.[120] 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.[121]
Prostaglandins, local hormones produced in the body, have diverse effects, 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 caused primarily by blood clots, and low doses of aspirin are seen as an effective medical intervention for acute myocardial infarction.
COX-1 and COX-2 inhibition
At least two different types of cyclooxygenase occur: COX-1 and COX-2. Aspirin irreversibly inhibits COX-1 and modifies the enzymatic activity of COX-2. COX-2 normally produces prostanoids, most of which are proinflammatory. Aspirin-modified PTGS2 produces lipoxins, most of which are anti-inflammatory.[122] Newer NSAID drugs, COX-2 inhibitors (coxibs), have been developed to inhibit only PTGS2, with the intent to reduce the incidence of gastrointestinal side effects.[14]
However, several of the new COX-2 inhibitors, such as rofecoxib (Vioxx), have been withdrawn in the last decade, after evidence emerged that PTGS2 inhibitors increase the risk of heart attack and stroke.[123][124] Endothelial cells lining the microvasculature in the body are proposed to express PTGS2, and, by selectively inhibiting PTGS2, prostaglandin production (specifically, PGI2; prostacyclin) is downregulated with respect to thromboxane levels, as PTGS1 in platelets is unaffected. Thus, the protective anticoagulative effect of PGI2 is removed, increasing the risk of thrombus and associated heart attacks and other circulatory problems. Since platelets have no DNA, they are unable to synthesize new PTGS once aspirin has irreversibly inhibited the enzyme, an important difference with reversible inhibitors.
Additional mechanisms
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.[125] In short, aspirin buffers and transports the protons. When high doses of aspirin are given, it may actually cause fever, owing to the heat 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 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, evidence is insufficient to show aspirin helps to fight infection.[126] More recent data also suggest salicylic acid and its derivatives modulate signaling through NF-κB.[127] NF-κB, a transcription factor complex, plays a central role in many biological processes, including inflammation.
Aspirin is readily broken down in the body to salicylic acid, which 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 of the effects of both salicylic acid and aspirin.[128][129] The acetyl portion of the aspirin molecule is not without its own targets. Acetylation of cellular proteins is a well-established phenomenon in the regulation of protein function at the post-translational level. Aspirin is able to acetylate several other targets in addition to COX isoenzymes.[130][131] These acetylation reactions may explain many hitherto unexplained effects of aspirin.
Hypothalamic-pituitary-adrenal activity
Aspirin, like other medications affecting prostaglandin synthesis, has profound effects on the pituitary gland, which indirectly affects a number of other hormones and physiological functions. Effects on growth hormone, prolactin,[132] and TSH (with relevant effect on T3 and T4) were observed directly.[133] Aspirin reduces the effects of vasopressin[134] and increases those of naloxone[135] upon the secretion of ACTH and cortisol by the hypothalamic-pituitary-adrenal axis (HPA axis), which has been suggested to occur through an interaction with endogenous prostaglandins and their role in regulating the HPA axis.[134]
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 eight to 24 hours. The increased pH and larger surface area of the small intestine causes aspirin to be absorbed rapidly there, which in turn allows more of the salicylate to dissolve. Owing 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.[136][137][138]
About 50–80% of salicylate in the blood is bound to albumin 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.[138]
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 it 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.[138]
Salicylates are excreted mainly by the kidneys as salicyluric acid (75%), free salicylic acid (10%), salicylic phenol (10%), and acyl glucuronides (5%), gentisic acid (< 1%), and 2,3-dihydroxybenzoic acid.[139] 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 2.0 to 4.5 hours.[140][141] When higher doses of salicylate are ingested (more than 4 g), the half-life becomes much longer (15–30 hours),[142] because the biotransformation pathways concerned with the formation of salicyluric acid and salicyl phenolic glucuronide become saturated.[143] Renal excretion of salicylic acid becomes increasingly important as the metabolic pathways become saturated, because it is extremely sensitive to changes in urinary pH. A 10- to 20-fold increase in renal clearance occurs when urine pH is increased from 5 to 8. The use of urinary alkalinization exploits this particular aspect of salicylate elimination.[144]
Plant extracts, including willow bark and spiraea, of which salicylic acid was the active ingredient, had been known to help alleviate headaches, pains, and fevers since antiquity. The father of modern medicine, Hippocrates (circa 460 – 377 BC), left historical records describing the use of powder made from the bark and leaves of the willow tree to help these symptoms.[145]
In 1763, Edward Stone, at Oxford, isolated the active ingredient of aspirin in his discovery of salicylic acid. A French chemist, Charles Frederic Gerhardt, was the first to prepare acetylsalicylic acid 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.[146] 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.
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.[147] In 1869, Schröder, Prinzhorn, and Kraut repeated both Gerhardt's (from sodium salicylate) and von Gilm's (from salicylic acid) syntheses and concluded 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.[148]
In 1897, chemists working at Bayer AG produced a synthetically altered version of salicin, derived from the species Filipendula ulmaria (meadowsweet), which caused less digestive upset than pure salicylic acid. The identity of the lead chemist on this project is a matter of controversy. Bayer states the work was done by Felix Hoffmann, but the Jewish chemist Arthur Eichengrün later claimed he was the lead investigator and records of his contribution were expunged under the Nazi regime.[12][149] The new drug, formally acetylsalicylic acid, was named Aspirin by Bayer AG after the original botanical name for meadowsweet, Spiraea ulmaria, derived from "acetyl" and Spirsäure, an old German name for salicylic acid derived from the Latin Spiraea ulmaria.[150] By 1899, Bayer was selling it around the world.[151] The popularity of aspirin grew over the first half of the 20th century, spurred by its supposed effectiveness in the wake of the Spanish flu pandemic of 1918. However, recent research suggests the high death toll of the 1918 flu was partly due to aspirin, though this is highly controversial and not widely accepted.[152] 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.[153][154]
The popularity of aspirin declined after the market releases of paracetamol (acetaminophen) in 1956 and ibuprofen in 1969.[155] 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 anticlotting agent that reduces the risk of clotting diseases.[156] Aspirin sales revived considerably in the last decades of the 20th century, and remain strong in the 21st century, because of its widespread use as a preventive treatment for heart attacks and strokes.[157]
As part of war reparations specified in the 1919 Treaty of Versailles following Germany's surrender after World War I, Aspirin (along with heroin) lost its status as a registered trademark in France, Russia, the United Kingdom, and the United States, where it became a generic name.[158][159][160] Today, aspirin is a generic word in Australia, France, India, Ireland, New Zealand, Pakistan, Jamaica, Colombia, the Philippines, South Africa, the United Kingdom and the United States.[161] Aspirin, with a capital "A", remains a registered trademark of Bayer in Germany, Canada, Mexico, and in over 80 other countries, where the trademark is owned by Bayer, using acetylsalicylic acid in all markets, but using different packaging and physical aspects for each.[162][163]
Compendial status
- United States Pharmacopeia[164]
- British Pharmacopoeia[165]
Veterinary use
Aspirin is sometimes used for pain relief or as an anticoagulant in veterinary medicine, primarily in dogs and sometimes horses, although newer medications with fewer side effects are generally used, instead.
Both dogs and horses are susceptible to the gastrointestinal side effects associated with salicylates, but it is a convenient treatment for arthritis in older dogs, and has shown some promise in cases of laminitis in horses.[166][167] It is no longer commonly used for cases of laminitis, as it could be counterproductive for treatment. Aspirin should be used in animals only under the direct supervision of a veterinarian; in particular, cats lack the glucuronide conjugates that aid in the excretion of aspirin, making it potentially toxic.[168] No clinical signs of toxicosis occurred when cats were given 25 mg/kg of aspirin every 48 hours for 4 weeks.[169] The dose recommended in cats for relief of pain and fever is 10 mg/kg every 48 hours.[170]
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- ^ Basu TK (1982). "Vitamin C-aspirin interactions". Int J Vitam Nutr Res Suppl 23: 83–90. PMID 6811490.
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- ^ Achhrish goel, Ruchi gupta Anubhav goswami Madhu soodan sharma Yogesh sharma (2011). "Pharmacokinetic Solubility And Dissolution Profile of Non-Steroidal Anti-Inflammatory Drugs" 2 (3).
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- ^ Hawley, S. A.; Fullerton, M. D.; Ross, F. A.; Schertzer, J. D.; Chevtzoff, C.; Walker, K. J.; Peggie, M. W.; Zibrova, D.; Green, K. A.; Mustard, K. J.; Kemp, B. E.; Sakamoto, K.; Steinberg, G. R.; Hardie, D. G. (2012). "The Ancient Drug Salicylate Directly Activates AMP-Activated Protein Kinase". Science 336 (6083): 918–922. doi:10.1126/science.1215327. PMC 3399766. PMID 22517326.
- ^ Raffensperger, Lisa (19 April 2012). "Clues to aspirin's anti-cancer effects revealed". New Scientist 214 (2862): 16. doi:10.1016/S0262-4079(12)61073-2.
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- ^ Caviezel, F.; Cattaneo, A. G.; Tell, A.; Corino, T.; Mascherpa, M. (1983). "The effect of acetylsalicylic acid and diclofenac on stimulated growth hormone and prolactin secretion in humans". International journal of clinical pharmacology, therapy, and toxicology 21 (10): 502–504. PMID 6642786.
- ^ Ramey, JN; Burrow, GN; Spaulding, SW; Donabedian, RK; Speroff, L; Frantz, AG (1976). "The effect of aspirin and indomethacin on the TRH response in man". The Journal of Clinical Endocrinology and Metabolism 43 (1): 107–14. doi:10.1210/jcem-43-1-107. PMID 820703.
- ^ a b Nye EJ, Hockings GI, Grice JE, Torpy DJ, Walters MM, Crosbie GV, Wagenaar M, Cooper M, Jackson RV; Hockings; Grice; Torpy; Walters; Crosbie; Wagenaar; Cooper; Jackson (1997). "Aspirin inhibits vasopressin-induced hypothalamic-pituitary-adrenal activity in normal humans". J. Clin. Endocrinol. Metab. 82 (3): 812–7. doi:10.1210/jc.82.3.812. PMID 9062488.
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- ^ Ferguson, RK; Boutros, AR (17 August 1970). "Death following self-poisoning with aspirin". Journal of the American Medical Association 213 (7): 1186–8. doi:10.1001/jama.213.7.1186. PMID 5468267.
- ^ Kaufman, FL; Dubansky, AS (April 1970). "Darvon poisoning with delayed salicylism: a case report". Pediatrics 49 (4): 610–1. PMID 5013423.
- ^ a b c Levy, G; Tsuchiya, T (31 August 1972). "Salicylate accumulation kinetics in man". New England Journal of Medicine 287 (9): 430–2. doi:10.1056/NEJM197208312870903. PMID 5044917.
- ^ 2,3-Dihydroxybenzoic acid is a product of human aspirin metabolism. Martin Grootveld and Barry Halliwell, Biochemical Pharmacology, Volume 37, Issue 2, 15 January 1988, pages 271–280, doi:10.1016/0006-2952(88)90729-0
- ^ Hartwig, Otto H (14 November 1983). "Pharmacokinetic considerations of common analgesics and antipyretics". American Journal of Medicine 75 (5A): 30–7. doi:10.1016/0002-9343(83)90230-9. PMID 6606362.
- ^ Done, AK (November 1960). "Salicylate intoxication. Significance of measurements of salicylate in blood in cases of acute ingestion". Pediatrics 26: 800–7. PMID 13723722.
- ^ 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.
- ^ Prescott LF, Balali-Mood M, Critchley JA, Johnstone AF, Proudfoot AT; Balali-Mood; Critchley; Johnstone; Proudfoot (1982). "Diuresis or urinary alkalinisation for salicylate poisoning?". Br Med J (Clin Res Ed) 285 (6352): 1383–6. doi:10.1136/bmj.285.6352.1383. PMC 1500395. PMID 6291695.
- ^ Dargan PI, Wallace CI, Jones AL.; Wallace; Jones (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.
- ^ Mary Bellis (16 June 2010). "History of aspirin". Inventors.about.com. Retrieved 11 May 2011.
- ^ Gerhardt, Ch. (1853). "Untersuchungen über die wasserfreien organischen Säuren" [Investigations into anhydrous organic acids]. Annalen der Chemie und Pharmacie (in German) 87: 149–179. doi:10.1002/jlac.18530870107. See especially pages 162-163.
- ^ von Gilm H (1859). "Acetylderivate der Phloretin- und Salicylsäure" [Acetyl derivatives of phloretic and salicylic acids]. Annalen der Chemie und Pharmacie (in German) 112 (2): 180–182. doi:10.1002/jlac.18591120207.
- ^ Schröder, Prinzhorn, Kraut K; Prinzhorn; Kraut (1869). "Ueber Salicylverbindungen" [On compounds of salicylic acid]. Annalen der Chemie und Pharmacie (in German) 150 (1): 1–20. doi:10.1002/jlac.18691500102. See especially pages 9-13; the structural formula of acetylsalicylic acid appears on p. 12.
- ^ Mahdi, JG; Mahdi, AJ, Mahdi, AJ, Bowen, ID (April 2006). "The historical analysis of aspirin discovery, its relation to the willow tree and antiproliferative and anticancer potential". Cell proliferation 39 (2): 147–55. doi:10.1111/j.1365-2184.2006.00377.x. PMID 16542349.
- ^ Singer, H. (1901). "Ueber Aspirin". Pflügers Archiv: European Journal of Physiology 84 (11–12): 527–546. doi:10.1007/BF01769129.
- ^ Jeffreys 2005, pp. 73
- ^ Starko, Karen M. (2009). "Salicylates and Pandemic Influenza Mortality, 1918–1919 Pharmacology, Pathology, and Historic Evidence". Clinical Infectious Diseases 49 (9): 1405–1410. doi:10.1086/606060. PMID 19788357.
- ^ Jeffreys 2005, pp. 136–142, 151–152
- ^ "Bayer patents aspirin – This Day in History – 3/6/1899". History.com. Retrieved 11 May 2011.
- ^ Jeffreys 2005, pp. 212–217
- ^ Jeffreys 2005, pp. 226–231
- ^ Jeffreys 2005, pp. 267–269
- ^ "Treaty of Versailles, Part X, Section IV, Article 298". 28 June 1919. pp. Annex, Paragraph 5. Retrieved 25 October 2008.
- ^ Mehta, Aalok (2005). "Aspirin". Chemical & Engineering News 83 (25). Retrieved 23 October 2008.
- ^ "The Centenary of Aspirin". Ul.ie. 6 March 1999. Retrieved 11 May 2011.
- ^ CBE Style Manual Committee; Huth, Edward J. (1994). Scientific Style and Format: The CBE Manual for Authors, Editors, and Publishers. Cambridge University Press. p. 164. ISBN 978-0-521-47154-1.
- ^ "Aspirin: the versatile drug". CBC News. 28 May 2009.
- ^ Cheng, Tsung O. (2007). "The History of Aspirin". Texas Heart Institute Journal 34 (3): 392–393. PMC 1995051. PMID 17948100.
- ^ Sigma Aldrich. "Aspirin". Retrieved 13 July 2009. [dead link]
- ^ British Pharmacopoeia. "Index BP 2009". Retrieved 13 July 2009.
- ^ Crosby, Janet Tobiassen (2006). "Veterinary Questions and Answers". About.com. Archived from the original on 8 September 2007. Retrieved 5 September 2007.
- ^ Cambridge H, Lees P, Hooke RE, Russell CS; Lees; Hooke; Russell (1991). "Antithrombotic actions of aspirin in the horse". Equine Vet J 23 (2): 123–7. doi:10.1111/j.2042-3306.1991.tb02736.x. PMID 1904347.
- ^ Lappin, Michael R., ed. (2001). Feline internal medicine secrets. Philadelphia: Hanley & Belfus. p. 160. ISBN 1-56053-461-3.
- ^ http://www.merckmanuals.com/vet/toxicology/toxicities_from_human_drugs/analgesics_toxicity.html
- ^ http://www.ansci.cornell.edu/plants/toxcat/toxcat.html
Further reading
- Jeffreys, Diarmuid (11 August 2005). Aspirin: The Remarkable Story of a Wonder Drug. Bloomsbury USA. ISBN 1-58234-600-3.
External links
|Wikimedia Commons has media related to Aspirin.
- NextBio Aspirin Entry
- Aspirin Cuts Cancer Rates
- The History of Aspirin
- Aspirin at The Periodic Table of Videos (University of Nottingham)
- How Aspirin works
- The science behind aspirin
- Take two: Aspirin, New uses and new dangers are still being discovered as aspirin enters its 2nd century. Shauna Roberts, American Chemical Society
- Ling, Greg (2005). "Aspirin". How Products are Made 1. Thomson Gale.
- U.S. National Library of Medicine: Drug Information Portal – Aspirin
- CDC – NIOSH Pocket Guide to Chemical Hazards – Acetylsalicylic Acid
UpToDate Contents
全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.
- 1. アスピリン:リウマチ性疾患における作用機序、主な毒性、および使用 aspirin mechanism of action major toxicities and use in rheumatic diseases
- 2. 心血管疾患および癌の一次予防におけるアスピリン aspirin in the primary prevention of cardiovascular disease and cancer
- 3. 静脈血栓塞栓症の患者における理論的根拠と無期限の抗凝固の適応 rationale and indications for indefinite anticoagulation in patients with venous thromboembolism
- 4. アテローム動脈硬化性心血管疾患の二次予防に使用するアスピリン aspirin for the secondary prevention of atherosclerotic cardiovascular disease
- 5. 成人におけるサリチル酸(アスピリン)中毒 salicylate aspirin poisoning in adults
English Journal
- Pannexin1 Single Nucleotide Polymorphism and Platelet Reactivity in a Cohort of Cardiovascular Patients.
- Stierlin FB1,2,3, Molica F1,2, Reny JL3,4, Kwak BR1,2, Fontana P3,5.
- Cell communication & adhesion.Cell Commun Adhes.2017 Dec;23(1):11-15. doi: 10.1080/15419061.2017.1282469.
- Mechanistic assessment of the analgesic, anti-inflammatory and antipyretic actions of Dalbergia saxatilis in animal models.
- Yemitan OK1, Adeyemi OO2.
- Pharmaceutical biology.Pharm Biol.2017 Dec;55(1):898-905. doi: 10.1080/13880209.2017.1283706.
- Effect of Cichorium intybus L. seed extract on renal parameters in experimentally induced early and late diabetes type 2 in rats.
- Pourfarjam Y1, Rezagholizadeh L1, Nowrouzi A1,2,3, Meysamie A4, Ghaseminejad S1, Ziamajidi N5, Norouzi D6.
- Renal failure.Ren Fail.2017 Nov;39(1):211-221. doi: 10.1080/0886022X.2016.1256317. Epub 2016 Nov 16.
- Antithrombotic regimens in patients with atrial fibrillation and coronary artery disease after percutaneous coronary intervention: A focused review.
- Chang KW1, Arbit B1, Hsu JC2.
- International journal of cardiology.Int J Cardiol.2017 Sep 15;243:263-269. doi: 10.1016/j.ijcard.2017.05.119. Epub 2017 Jun 2.
Japanese Journal
- アスピリンによる小腸粘膜傷害 : カプセル内視鏡による評価 (AYUMI 薬剤起因性消化管傷害Update)
- 遠藤 宏樹,中島 淳
- 医学のあゆみ 243(11・12), 963-967, 2012-12-22
- 低用量アスピリンの上部消化管傷害 : 胃内pH,ヘリコバクター感染症からみた傷害発症機序 (AYUMI 薬剤起因性消化管傷害Update)
- 魚谷 貴洋,杉本 光繁,古田 隆久
- 医学のあゆみ 243(11・12), 947-951, 2012-12-22
- アスピリン・NSAIDs胃粘膜傷害の発症機序 : 動物実験からの推察 (AYUMI 薬剤起因性消化管傷害Update)
- 竹内 孝治
- 医学のあゆみ 243(11・12), 941-946, 2012-12-22
Related Links
- 1897年8月、バイエルの一人の化学者によって開発されたアスピリンは、その後瞬く間に全世界に広がりました。今では、解熱鎮痛薬の代名詞として使用されるほど多くの人に愛用されています。おそらく世界でいちばん知名度の高い薬です。
- 13/10/22 バイエルアスピリンwebキャンペーン 「頭痛顔偉人グランプリ」開催中(-13年12月1日まで) 五十嵐先生の頭痛解説 頭痛はタイプによって原因も対処法も様々。まず頭痛について知ることが症状改善の第一歩。医学博士、五十嵐 ...
- ↓ASPIRIN WebSite↓ PC ENTER myspace ↓ASPIRIN WebSite↓ PC ENTER myspace
Related Pictures
|「アスピリン」「acetylsalicylic acid」
|「aspirin aluminum」「aspirin-induced bronchoconstriction」
- 英
- aspirin
- 商
- アスファネート配合、イスキア配合、サリチゾン、ゼンアスピリン、ニチアスピリン、ニトギス配合、バイアスピリン、バッサミン配合、バファリン配合、ファモター配合
- 関
- アスピリン喘息、アセチルサリチル酸 acetylsalicylic acid ASA、アスピリン中毒
- アセチルサリチル酸の酢酸エステル
- 酸性
- サリチル酸系
- 抗炎症薬
- 抗血栓薬
- ピリン系解熱鎮痛薬ではないので、ピリン過敏症はきたさない。
- 脳の体温調整中枢を抑制して解熱。感覚中枢の興奮を抑制? → 鎮痛 1.5g/day
- 少量で血小板凝集を低下。血栓、塞栓を予防 → 40-100mg/day
- 関節リウマチにおける抗炎症には → 3g/day
- アスピリンは弱酸性。胃でプロトンを放出。大部分は回腸で吸収される。
- アスピリンは組織、血漿、特に肝臓に存在するエステラーゼにより30分以内にサリチル酸塩となり抗炎症作用を呈する。25%は酸性?、抱合されて排出される。25%は未変化のまま排泄される。アルカリ尿で排泄されやすい。Cox抑制作用は不可逆的アセチル化反応による。持続時間は血漿半減期に関係しない。半減期は短いが、作用は持続することに注意する。
- シクロオキシゲナーゼを不可逆的に不活化する。
- ライ症候群との関連に注意。
- バイアスピリン錠100mg
- 1. 本剤の成分又はサリチル酸系製剤に対し過敏症の既往歴のある患者
- 2. 消化性潰瘍のある患者[プロスタグランジン生合成抑制作用により,胃の血流量が減少し,消化性潰瘍を悪化させることがある.(ただし,「慎重投与」の項参照)]
- 3. 出血傾向のある患者[血小板機能異常が起こることがあるため,出血傾向を助長するおそれがある.]
- 4. アスピリン喘息(非ステロイド性消炎鎮痛剤等による喘息発作の誘発)又はその既往歴のある患者[重篤なアスピリン喘息発作を誘発させることがある.]
- 5. 出産予定日12週以内の妊婦[「妊婦,産婦,授乳婦等への投与」の項参照]
- 6. 低出生体重児,新生児又は乳児[「小児等への投与」の項参照]
- 甲状腺クリーゼに対してアスピリンを解熱薬として使うと、サイログロブリンとトリヨードサイロニンの結合を阻害し、free T3の濃度が上昇して病状を悪化させるので使用しない
- バイアスピリン錠100mg
「acetylsalicylic acid」
- 関
- aspirin
- 関
- Aspirin
- 関
- Aspirin


text:
A good while back, I did a post here pontificating about how the question 'Where do you get your ideas from?' was not a particularly good query to fire at a writer.
This is the sequel to that post, in which I answer the question in question. Just thought it'd be fun. Might also help to illustrate my case that ideas are the easy bit, coming as they do from everywhere, all the time, unpredictably.
So, here's where the idea for every piece of fiction I've sold came from, in chronological order of publication.
Farm Animal, my first published story, appeared in the UK's venerable sf magazine Interzone a long, long time ago. It has a unique, and unusually simple, origin in the context of my fiction output: it's loosely based on a dream I had. It was a kind of creepy, not very nice, dream so we won't go into any more details except to say it involved a human-pig hybrid. The hard bit, as ever, was turning that seed into a narrative of some sort, and in the process the story became about the transformation of a human into a pig. (Sidenote: I remember being quite pleased with myself, at that presumptuous age, for coming up with a title that reverses Animal Farm, in which pigs transform into humans, just as my story reverses that transformation. Doesn't seem quite so clever now.)
Gibbons, my second published story, appeared in another UK magazine: The Third Alternative – still going, under the new title Black Static. Its origin is also unique in this list, in that it comes from my own direct, personal experience. In my early twenties I spent three months in Borneo, finding, following and sound-recording gibbons in a remote part of the rainforest. In hindsight, as you might expect, it was a powerful, rather formative experience in various ways (including career-wise, since it would later result in me getting a job that sent me to many other unusual, out of the way bits of the world), though at the time – as with many such experiences – I didn't fully appreciate its significance. What did imprint itself on my mind even then, though, was the potent atmosphere and character of the place. It took years for the story that gave voice to my impressions of the Bornean rainforest to take shape, but Gibbons was the eventual result.
Winterbirth, and the Godless World trilogy of which it is the first part, has a messy kind of idea-origin. I knew I wanted to try writing novels, and I was instinctively interested in the possibility of a fantasy trilogy. I needed an imaginative nudge of some sort to get the process of world, character and story development going, and it came from the TV, in a way. This was way back when the Balkans, and the former Yugoslavia in particular, were in post-Communist meltdown and filling our TV screens and newspapers with stories and images of horrendous and cruel violence. Because I was even then a history nerd, I knew a lot of what was happening was the indirect fruit of bitter rivalries, enmities and events that went back many, many hundreds of years, and I was struck by the thought that it might be interesting to write about a fantasy world similarly torn apart by long-suppressed, half-hidden enmities that were somehow allowed to re-emerge.
Now, that initial idea got considerably complicated and diluted by the aforementioned process of world, character and story development. It provided the impetus for the process, but was itself changed and elaborated by it. Such things happen, once you get into the flow of turning a small spark into a fully fledged fire. But that's what ideas are for really: they start the process, but unlike a chemical catalyst, they don't have to survive that process unchanged.
Beyond the Reach of His Gods is a short story that appeared in the anthology Rage of the Behemoth, from Rogue Blades Entertainment. Much to my delight, it's since been reprinted in the excellent online magazine Lightspeed, so you can read the whole thing for free over there if you like. This was the first time I'd been invited/commissioned to write a story for an anthology, and the brief was highly specific: heroic fantasy involving a giant monster set in one of several specific environments. I had no pre-existing ideas that fitted the bill (hardly surprising!), so the idea for this story had to be kind of 'forced'. Except it came to me very easily, very quickly and very completely. I've no idea how that happens, but now and again it does: I just looked at the brief, thought about it for a bit, and the setting, characters, monster and the basic skeleton of the plot just turned up in my head. Very nice, and forunate really, since I would probably have turned down the invitation had things not bubbled up so easily, and had the story they suggested not struck me as being fun to write.
Flint was another short story for an anthology – Speculative Horizons, from Subterranean Press, edited by Patrick St-Denis. Again, I was asked if I would contribute, but this time there were no prescriptions regarding subject matter or even specific genre. So I pulled out a partially developed idea I'd been keeping on a mental shelf for ages, and used this as the opportunity to turn it into an actual story. That idea had its roots in my non-fiction reading: books like The Golden Bough, After The Ice and Shamanism. In learning and thinking about early magical beliefs, hunter-gatherer societies and the deep, deep past of human society and imagination, it struck me that a Stone-Age shaman would make an interesting central character for some kind of story. I knew very early on that his name would be Flint, but much of the detail of his adventures only got filled in when Patrick asked me if I fancied writing a story for his anthology …
The Edinburgh Dead has a very clear and fairly simple idea-origin. Having grown up in Edinburgh, and living there again now after a good few years away, I know a lot about its history and geography. Mind you, even people who've never been here have heard of Burke & Hare, the infamous baddies who murdered a lot of people so that they could sell their corpses to lecturers for dissection in anatomy classes in the early 19th century. For whatever reason, one day while musing on Edinburgh's rich and complicated history, I just asked myself: 'What if there were other people around back then, who wanted corpses for a different kind of experiment?'. From that question, after a good deal of research and the addition of a good many other influences, the whole novel emerged. And, inevitably, Burke and Hare stayed in the mix as characters in the story.
Rogue Trooper, the comic I'm writing for IDW (first issue in comic shops and on Comixology on Feb 26th!), is a different kettle of fish, idea-wise. This is a pre-existing character and milieu that I was asked to re-imagine. So the ideas required are of a different kind: what games can I play, what details can I add or subtract, what themes can I develop, with this already-established character? Those kind of ideas just come from looking at what's there already, thinking back or re-visiting all the previous Rogue Trooper stories I read as a youth, applying my personal instincts as a writer to the property. To be honest, lots and lots of possibilities presented themselves to me as soon as I became aware of the opportunity, so it wasn't too difficult. When someone else has done the hard work of creating a strong character, setting and framework, riffing on it is pretty straightforward (at least in terms of ideas, if not execution; believe me, I can now say from personal experience that writing comics is not straightforward or effortless!).
The Free will be published this October by Orbit, and it's kind of fitting that it comes last on this list because in one sense it's an extreme example on the original idea front. This book, alone of all the fictions on this list, has shed its originating idea like a snake shedding a skin. Literally no trace of the idea to which it can trace its roots remains in the novel that will be published. Weird, huh? Anyway, one day – or night, I think perhaps I was trying to go to sleep – a scene just popped into my head. In an underground cavern, someone discovers a prisoner, trapped in a huge cage. That was it. This was way back when I was still writing the Godless World trilogy. I had half a notion I might try writing another trilogy after I was finished with that one (a notion I soon thought better of!), and that single, unformed scene became the seed from which I gradually grew the outline of a whole plot, world, magic system, characters – I didn't have a full trilogy worked out in detail, but I had a lot of stuff churning around in my head.
Except, I wrote The Edinburgh Dead instead. But the story-stuff that had sprung from that single imagined scene kept stewing in my thinking parts, and kept changing. In the plot I'd loosely imagined, there were a set of secondary characters – mercenaries – who struck me as interesting. To cut a long story short, I ended up pitching an idea focused upon them to the publisher as a stand-alone novel. The Free. The world in which they operate is not the one I dreamed up for that trilogy; the magic system is utterly different; there's not a single character who has survived from my earlier musings into the text of the The Free; at no point does anyone even go underground, let alone discover a subterranean chamber with a caged prisoner in it. (But who's to say what might happen, should I ever write any more stories about The Free?)
So there you are. I get my ideas from dreams, from personal experiences, from current affairs, from history, from commissions, from non-fiction books, from other people's creations, from random scenes popping into my head. And I could add, in respect of fictions I've thought about or am currently pondering, which may or may not ever see the light of day: I also get them from idle reflections on the under-use of particular mythical creatures in fiction, consciously setting myself the challenge of coming up with an idea for a TV/radio series, writing tasks based on a single word set by tutors on a short course I did many years ago, looking at maps, etc. etc.
All seems clear enough. Question answered.

subset: commoncrawl


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By Zhoujie Zhang
Spider Chair (SQN1-F2C) Stainless Steel | The Stainless Steel Collection, 2011
# 304 Stainless Steel, Super Mirror Finish
60L × 60W × 75H cm
23.62L × 23.62W × 29.53H in
Edition of 12
Price Available Upon Request
The Spider Chair is a perfect example of Zhoujie's philosophy of ACTIONLESS. Like a force of an airplane, polymerizing inward and flowing with natural tendency. The digital generation process only took a few seconds, but the continuous logical deduction behind it took over 3 years. Until natural growth and function perfectly combined, the work is completed. This product demonstrates the natural beauty of digital logic.
With his practice dedicated to the development of a digitalized fabrication system, Zhoujie's goal has been to create a system with an ability to transform digital programs into real objects. In the near future, people will be able to participate in the creation; design a customized chair through the digital system and select different materials of their choice. This brand new, artificial intelligence design concept will fit better into the life and preferences of each individual, and, the interaction between product and human will be deepened. The process of design will evolve from single physical phase to a systematic level. Zhoujie's goal for his future collection of works is to engineer designs that utilize progressive elements such as macromolecular materials and titanium.
Zhoujie's works and design principles are based on spontaneity, taken from the philosophies of Taoism. This philosophy reflects his understanding of ACTIONLESS, which pays respect to the logic of mathematics and the laws of a digital environment.
As an independent designer, Zhoujie Zhang believes that good design is inspired by process. By continuously forming new concepts throughout the course of development and production, the creation is a constant progression of its evolution.
"Through my design I'd like to build new path towards our digital future and eventually create a system that could measure, design, produce, test as well as market these new possibilities. Following on from the first and second industrial revolution, we are now experiencing a third one, a digital revolution. I'm going to dive into it and I'm ready for a long march." —-Zhoujie Zhang


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In The Box
- Lastolite Fabric Grid
- Carrying Case
Product Features
This Lastolite Fabric Grid is designed to control light spread from your small Ezybox II Square Softbox. The grid features a degree spread of 45° with 2 x 2 x 2" cells. It easily attaches to the face of the softbox via hook-and-loop fasteners and has a durable nylon fabric construction. When not being used, it easily stores in the included carrying bag.
Product Specification
|Nylon fabric


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Onetime member of the Yellow Dogs reportedly gunned downed ex-mates early Monday morning
A former member of the Brooklyn-based dance-punk group the Yellow Dogs reportedly killed three of the group's musicians early Monday morning. The man, whom the New York Post identified as Raefe Ahkbar, used a semi-automatic rifle to shoot the men, wound another and kill himself. He carried out the massacre at an apartment in Bushwick, Brooklyn, where some of the band members were believed to have lived. The band had emigrated to the U.S. from Tehran, Iran, in 2011.
SXSW 2010: 27 Tweet-Length Reports, Including the Yellow Dogs
The band reportedly ousted Ahkbar after he stole money and equipment, according to the Post. An anonymous source told the paper that prior to the shooting, "He said something like 'Why did you bring me over here [from Iran] and then throw me out?'" In retaliation, he allegedly killed 27-year-old guitarist Soroush Farazmand in a second-floor bedroom, then ascended to the third floor, where he shot 35-year-old vocalist Ali Eskandarian and drummer Arash Farazmand, whose age is unknown. He also wounded Sasan Sadeghpourosko, who was outside the building and is not believed to be a member of the band. The Yellow Dogs' guitarist Siavash Karampour and bassist Koory Mirz were not injured. A neighbor said he heard 45 gunshots.
"You always see them coming in and out of their house with their musical instruments in cases. They seemed like great kids, never bothered anybody," neighbor Martin Greenman, 63, told the Post. "They resembled each other with the curly black hair and the tight jeans. They looked like typical hipsters."
The group appeared in the 2009 movie No One Knows About Persian Cats, which won a prize at Cannes. The band's song "New Century" appeared on its soundtrack. The group was also featured in a CNN piece on artists in the Middle East. "They think I'm an anarchist," guitarist Karampour told the interviewer. Later he said, "They're like my brothers. They're more close than my brothers." The report said that musicians who play rock music, which is deemed "un-Islamic" in the country, could be jailed and beaten.
The group moved to New York City permanently in 2010. In a Tweet-length review of the band's gig at SXSW that year, Rolling Stone wrote, " Iranian post-punkers ride spidery bass lines, galloping hi-hats & garage-fucked guitar. Small crowd, great sound."
The Yellow Dogs' video for "This City," a track they released last year, is below.


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Posted 7 years ago
(1 item)
I was left these two Antique Japanese Dolls from my late mother. They were given to her by my dad over 50 years ago when he was in the service in occupied japan. They are both in their original mirrored back glass and wooden display cases. The cases measure about 10 1/2" high x 5 3/8" deep x 7 " across the front. The dolls inside have never been out of these cases. They are on a wooden base and there is a small wooden dowl of some kind which somes through the bottom of the case.
I am looking for any information someone can help me with. Such as how old are they? Is there a name for this type of doll? What materials are they likely to be made of? What would the approximate value be for insurance purposes? I would appreciate any help someone could give me that is more knowledgeable than myself.


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'The Hobbit: An Unexpected Journey' (Dec. 21)
Stars: Martin Freeman, Ian McKellen, Andy Serkis Director: Peter Jackson Why we're excited: America can only live on "Lord of the Rings" Blu-ray re-releases for only so long. Jackson's first film in this planned trilogy focuses on Bilbo Baggins (Freeman, so good in BBC's "Sherlock" series) journeying (unexpectedly) to reclaim a treasure stolen by the dragon Smaug. Expect the return of former "Rings" cast members (McKellen, Cate Blanchett, Orlando Bloom, et al.) and enough inspiration to work up the courage to ask for tickets to 2013's badly named follow-up, "The Hobbit: The Desolation of Smaug."
Warner Bros.
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Penwortham Gala - May 2016


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Three electrocutions in July and several reported shocks have caused concern about electrical wiring installed decades ago on boat docks at the Lake of the Ozarks, Mo. Electricians in the lake area are in demand as owners of property around the lake — especially older homes and resort complexes — strive to make their docks safe.
Recently, the Kansas City Star reported fire marshals who inspect the wiring are in demand and hardware stores are running out of electrical supplies, as fire departments and the Missouri State Highway Patrol caution dock owners to secure their docks.
Read the full article at KansasCity.com.
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