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{{for|the Persian-language TV series|Aspirin (TV series){{!}}''Aspirin'' (TV series)}}
{{distinguish|Robert Asprin}}
{{Use dmy dates|date=
{{Good article}}
{{Infobox drug
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<!-- Clinical data -->
| pronounce =
| tradename = [[Bayer#Aspirin|Bayer Aspirin]], others
| Drugs.com = {{drugs.com|monograph|aspirin}}
| MedlinePlus = a682878
| DailyMedID = Acetylsalicylic acid
| pregnancy_AU = C
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| pregnancy_category =
| routes_of_administration = [[Oral administration|Oral]], [[rectal administration|rectal]]
| class = [[Nonsteroidal anti-inflammatory drug
| ATC_prefix = A01
| ATC_suffix = AD05
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<!-- Legal status -->
| legal_AU = OTC
| legal_AU_comment = / Schedule 2, 4, 5, 6<ref>{{cite web | title=OTC medicine monograph: Aspirin tablets for oral use | website=Therapeutic Goods Administration (TGA) | date=21 June 2022 | url=https://www.tga.gov.au/resources/publication/publications/otc-medicine-monograph-aspirin-tablets-oral-use | access-date=4 April 2023}}</ref><ref>{{cite web | title=Poisons Standard October 2022 | website=Australian Government Federal Register of Legislation | date=26 September 2022 | url=https://www.legislation.gov.au/Series/F2022L01257 | access-date=9 January 2023}}</ref>
| legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F-->
| legal_BR_comment =
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| NIAID_ChemDB =
| PDB_ligand = AIN
| synonyms = {{ubl|2-acetoxybenzoic acid|''o''-acetylsalicylic acid|acetylsalicylic acid|acetyl salicylate|monoacetic acid ester of salicylic acid<ref>{{cite journal|journal=Bulletin of the History of Medicine|title=What's in a Name? Aspirin and the American Medical Association|first=Jan|last=McTavish|volume=61|number=3|date=Fall 1987|url=https://www.jstor.org/stable/44442097}}</ref>}}
<!-- Chemical and physical data -->
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One common [[adverse effect]] is an [[upset stomach]].<ref name=AHFS/> More significant side effects include [[stomach ulcer]]s, [[stomach bleeding]], and worsening [[asthma]].<ref name=AHFS/> Bleeding risk is greater among those who are older, drink [[Alcohol (drug)|alcohol]], take other NSAIDs, or are on other [[anticoagulant|blood thinners]].<ref name=AHFS/> Aspirin is not recommended in the last part of [[pregnancy]].<ref name=AHFS/> It is not generally recommended in children with [[infection]]s because of the risk of [[Reye syndrome]].<ref name=AHFS/> High doses may result in [[tinnitus|ringing in the ears]].<ref name=AHFS/>
A [[Precursor (chemistry)|precursor]] to aspirin found in the bark of the [[willow tree]] (genus ''Salix'') has been used for its health effects for at least 2,400 years.<ref name=Jon2015>{{cite book |vauthors = Jones A |title=Chemistry: An Introduction for Medical and Health Sciences|date=2015|publisher=John Wiley & Sons|isbn=978-0-470-09290-3|pages=5–6|url=https://books.google.com/books?id=ubE0ILq_aDQC&pg=PA6}}</ref><ref>{{cite book |vauthors = Ravina E |title=The Evolution of Drug Discovery: From Traditional Medicines to Modern Drugs |date=2011 |publisher=John Wiley & Sons |isbn=978-3-527-32669-3 |page=24 |url=https://books.google.com/books?id=iDNy0XxGqT8C&pg=PA24}}</ref> In 1853, chemist [[Charles Frédéric Gerhardt]] treated the medicine [[sodium salicylate]] with [[acetyl chloride]] to produce acetylsalicylic acid for the first time.<ref name="Jeffreys2008">{{cite book |url=https://books.google.com/books?id=a9gkBwAAQBAJ |title=Aspirin the remarkable story of a wonder drug. |vauthors=Jeffreys D |date=2008 |publisher=Bloomsbury Publishing USA |isbn=978-1-59691-816-0 |archive-url=https://web.archive.org/web/20170908213430/https://books.google.com/books?id=a9gkBwAAQBAJ |archive-date=8 September 2017 |url-status=}}{{rp|46–48}}</ref> Over the next 50 years, other chemists, mostly of the German company [[Bayer]], established the chemical structure and devised more efficient production methods.<ref name=Jeffreys2008/>{{rp|69–75}}
Aspirin is available [[Over-the-counter drug|without medical prescription]] as a proprietary or [[generic medication]]<ref name=AHFS/> in most jurisdictions. It is one of the most widely used medications globally, with an estimated {{convert|40000|tonne}} (50 to 120 billion [[Tablet (pharmacy)|pills]]){{Clarify|date=October 2022|reason=300mg? 75mg? Both common sizes}} consumed each year,<ref name="Jon2015" /><ref name="COX2002">{{cite journal|vauthors=Warner TD, Mitchell JA|date=October 2002|title=Cyclooxygenase-3 (COX-3): filling in the gaps toward a COX continuum?|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=99|issue=21|pages=13371–3|bibcode=2002PNAS...9913371W|doi=10.1073/pnas.222543099 |pmc=129677|pmid=12374850|doi-access=free | title-link = doi }}</ref> and is on the [[WHO Model List of Essential Medicines|World Health Organization's List of Essential Medicines]].<ref name="
==Brand vs. generic name==
In 1897, scientists at the [[Bayer]] company began studying acetylsalicylic acid as a less-irritating replacement medication for common salicylate medicines.<ref name=Jeffreys2008/>{{rp|69–75}}<ref name="Distillations">{{cite magazine | vauthors = Dick B |title=Hard Work and Happenstance |url=https://www.sciencehistory.org/distillations/magazine/hard-work-and-happenstance |magazine=Distillations |publisher=[[Science History Institute]] |date=2018 |volume=4 |issue=1 |pages=44–45 }}</ref> By 1899, Bayer had named it "Aspirin" and
Aspirin's popularity grew over the first half of the 20th century, leading to competition between many brands and formulations.<ref name="ACS">{{cite magazine |title=Aspirin |magazine=Chemical & Engineering News |date=20 June 2005 |volume=83 |issue=25 |url=https://pubsapp.acs.org/cen/coverstory/83/8325/8325aspirin.html }}</ref> The word ''Aspirin'' was Bayer's brand name; however, their rights to the [[trademark]] were [[Generic trademark|lost or sold in many countries]].<ref name=ACS/> The name is ultimately a blend of the prefix '''a'''(cetyl) + '''spir''' ''[[Spiraea]]'', the meadowsweet plant genus from which the acetylsalicylic acid was originally derived at Bayer + '''-in''', the common chemical suffix.{{Citation needed|date=April 2024}}
==Chemical properties==
Aspirin decomposes rapidly in solutions of [[ammonium acetate]] or the [[acetate]]s, [[carbonate]]s, [[citrate]]s, or [[hydroxide]]s of the [[alkali metals]]. It is stable in dry air, but gradually [[hydrolyses]] in contact with moisture to [[acetic acid|acetic]] and [[salicylic acid]]s. In solution with alkalis, the hydrolysis proceeds rapidly and the clear solutions formed may consist entirely of acetate and salicylate.<ref>{{cite encyclopedia |veditors = Reynolds EF |encyclopedia=Martindale: the extra pharmacopoeia|edition=28th|year=1982|pages=[https://archive.org/details/extrapharmacopoe28mart/page/234 234–82]|title=Aspirin and similar analgesic and anti-inflammatory agents|publisher=Rittenhouse Book Distributors|isbn=978-0-85369-160-0 |url=https://archive.org/details/extrapharmacopoe28mart/page/234}}</ref>
Like [[flour mill]]s, factories producing aspirin tablets must control the amount of the powder that becomes airborne inside the building, because [[dust explosion|the powder-air mixture can be explosive]]. The [[National Institute for Occupational Safety and Health]] (NIOSH) has set a [[recommended exposure limit]] in the United States of 5{{nbsp}}mg/m<sup>3</sup> (time-weighted average).<ref>{{
===Synthesis===
The synthesis of aspirin is classified as an [[ester]]ification 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-OCOCH<sub>3</sub>). 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 demonstrated in undergraduate teaching labs.<ref>{{
[[File:Aspirin synthesis.svg|thumb|Aspirin synthesis|center|490px]]Reaction between acetic acid and salicylic acid can also form aspirin but this esterification reaction is reversible and the presence of water can lead to hydrolysis of the aspirin. So, an anhydrous reagent is preferred.<ref>{{
;Reaction mechanism
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There was only one proven polymorph '''Form I''' of aspirin, though the existence of another polymorph was debated since the 1960s, and one report from 1981 reported that when crystallized in the presence of aspirin ''anhydride'', the [[diffractogram]] of aspirin has weak additional peaks. Though at the time it was dismissed as mere impurity, it was, in retrospect, '''Form II''' aspirin.<ref name="Bučar-2015">{{cite journal | vauthors = Bučar DK, Lancaster RW, Bernstein J | title = Disappearing polymorphs revisited | journal = Angewandte Chemie | volume = 54 | issue = 24 | pages = 6972–6993 | date = June 2015 | pmid = 26031248 | pmc = 4479028 | doi = 10.1002/anie.201410356 }}</ref>
'''Form II''' was reported in 2005,<ref>{{cite journal | vauthors = Vishweshwar P, McMahon JA, Oliveira M, Peterson ML, Zaworotko MJ | title = The predictably elusive form II of aspirin | journal = Journal of the American Chemical Society | volume = 127 | issue = 48 | pages = 16802–16803 | date = December 2005 | pmid = 16316223 | doi = 10.1021/ja056455b
In form I, pairs of aspirin molecules form centrosymmetric [[Dimer (chemistry)|dimers]] through the [[acetyl]] groups with the (acidic) [[methyl]] proton to [[carbonyl]] [[hydrogen bond]]s. In form II, each aspirin molecule forms the same hydrogen bonds, but with two neighbouring molecules instead of one. With respect to the hydrogen bonds formed by the [[carboxylic acid]] groups, both polymorphs form identical dimer structures. The aspirin polymorphs contain identical 2-dimensional sections and are therefore more precisely described as polytypes.<ref>{{cite web |title=Polytypism - Online Dictionary of Crystallography |url=http://reference.iucr.org/dictionary/Polytypism |website=reference.iucr.org}}</ref>
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===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
Low-dose aspirin use irreversibly blocks the formation of [[thromboxane A2|thromboxane A<sub>2</sub>]] 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 in people who have had a heart attack, unstable angina, ischemic stroke or transient ischemic attack.<ref>{{cite web |url=http://www.americanheart.org/presenter.jhtml?identifier=4456 |title=Aspirin in heart attack and stroke prevention |access-date=8 May 2008 |publisher=American Heart Association |archive-url=https://web.archive.org/web/20080331031146/http://www.americanheart.org/presenter.jhtml?identifier=4456 |archive-date=31 March 2008 }}</ref> 40{{nbsp}}mg of aspirin a day is able to inhibit a large proportion of maximum thromboxane A<sub>2</sub> release provoked acutely, with the prostaglandin
Prostaglandins, local [[hormone]]s produced in the body, have diverse effects, including the transmission of pain information to the brain, modulation of the [[hypothalamus|hypothalamic]] thermostat, and inflammation. Thromboxanes are responsible for the aggregation of platelets that form [[clot|blood clots]]. Heart attacks are caused primarily by blood clots, and low doses of aspirin are seen as an effective medical intervention to prevent a second acute myocardial infarction.<ref name="pmid19482214">{{cite journal
===COX-1 and COX-2 inhibition===
At least two different types of [[cyclooxygenase]]s, [[COX-1]] and [[COX-2]], are acted on by aspirin. Aspirin irreversibly inhibits COX-1 and modifies the enzymatic activity of COX-2. COX-2 normally produces [[prostanoid]]s, most of which are proinflammatory. Aspirin-modified
Several COX-2 inhibitors, such as [[rofecoxib]] (Vioxx), have been withdrawn from the market, after evidence emerged that
Furthermore, aspirin, while inhibiting the ability of COX-2 to form pro-inflammatory products such as the [[prostaglandins]], converts this enzyme's activity from a prostaglandin-forming cyclooxygenase to a [[lipoxygenase]]-like enzyme: aspirin-treated COX-2 metabolizes a variety of [[polyunsaturated fatty acids]] to hydroperoxy products which are then further metabolized to [[specialized proresolving mediators]] such as the aspirin-triggered [[lipoxin]]s, aspirin-triggered [[resolvins]], and aspirin-triggered [[maresin]]s. These mediators possess potent anti-inflammatory activity. It is proposed that this aspirin-triggered transition of COX-2 from cyclooxygenase to lipoxygenase activity and the consequential formation of specialized proresolving mediators contributes to the anti-inflammatory effects of aspirin.<ref name="pmid25895638">{{cite journal | vauthors = Romano M, Cianci E, Simiele F, Recchiuti A | title = Lipoxins and aspirin-triggered lipoxins in resolution of inflammation | journal = European Journal of Pharmacology | volume = 760 | pages = 49–63 | date = August 2015 | pmid = 25895638 | doi = 10.1016/j.ejphar.2015.03.083 }}</ref><ref name="pmid23747022">{{cite journal | vauthors = Serhan CN, Chiang N | title = Resolution phase lipid mediators of inflammation: agonists of resolution | journal = Current Opinion in Pharmacology | volume = 13 | issue = 4 | pages = 632–40 | date = August 2013 | pmid = 23747022 | pmc = 3732499 | doi = 10.1016/j.coph.2013.05.012 }}</ref><ref name="pmid26546723">{{cite journal | vauthors = Weylandt KH | title = Docosapentaenoic acid derived metabolites and mediators - The new world of lipid mediator medicine in a nutshell | journal = European Journal of Pharmacology | volume = 785 | pages = 108–115 | date = August 2016 | pmid = 26546723 | doi = 10.1016/j.ejphar.2015.11.002 }}</ref>
===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.<ref name="SomasundaramS">{{cite journal | vauthors = Somasundaram S, Sigthorsson G, Simpson RJ, Watts J, Jacob M, Tavares IA, Rafi S, Roseth A, Foster R, Price AB, Wrigglesworth JM, Bjarnason I
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.<ref>{{cite journal | vauthors = Hawley SA, Fullerton MD, Ross FA, Schertzer JD, Chevtzoff C, Walker KJ, Peggie MW, Zibrova D, Green KA, Mustard KJ, Kemp BE, Sakamoto K, Steinberg GR, Hardie DG
==Formulations==
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*Buffered formulations containing aspirin with one of many buffering agents.
*Formulations of aspirin with vitamin C (ASA-VitC)
*A phospholipid-aspirin complex liquid formulation, PL-ASA. {{As of|2023}} the phospholipid coating was being trialled to determine if it caused less gastrointestinal damage.<ref name=franchi>{{cite journal | vauthors = Franchi F, Schneider D, Prats J, Fan W, Rollini F, Been L, Taatjes-Sommer H, Deliargyris E, Angiolillo D
==Pharmacokinetics==
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As much as 80% of therapeutic doses of salicylic acid is [[metabolism|metabolized]] in the [[liver]]. [[Conjugated system|Conjugation]] with [[glycine]] forms [[salicyluric acid]], and with [[glucuronic acid]] to form two different glucuronide esters. The conjugate with the acetyl group intact is referred to as the ''acyl glucuronide''; the deacetylated conjugate is the ''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 pathway]]s become saturated and [[kidney|renal]] excretion becomes increasingly important.<ref name="G Levy"/>
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|2,3-dihydroxybenzoic acid]].<ref name="pmid3342084">{{cite journal | vauthors = Grootveld M, Halliwell B | title = 2,3-Dihydroxybenzoic acid is a product of human aspirin metabolism | journal = Biochemical Pharmacology | volume = 37 | issue = 2 | pages = 271–80 | date = January 1988 | pmid = 3342084 | doi = 10.1016/0006-2952(88)90729-0 }}</ref> When small doses (less than 250{{nbsp}}mg in an adult) are ingested, all pathways proceed by first-order kinetics, with an elimination half-life of about 2.0 h to 4.5 h.<ref name="O Hartwig">{{cite journal | vauthors = Hartwig-Otto H | title = Pharmacokinetic considerations of common analgesics and antipyretics | journal = The American Journal of Medicine | volume = 75 | issue = 5A | pages = 30–7 | date = November 1983 | pmid = 6606362 | doi = 10.1016/0002-9343(83)90230-9 }}</ref><ref name="AK Done">{{cite journal | vauthors = Done AK | title = Salicylate intoxication. Significance of measurements of salicylate in blood in cases of acute ingestion | journal = Pediatrics | volume = 26 | pages = 800–7 | date = November 1960 | doi = 10.1542/peds.26.5.800 | pmid = 13723722 | s2cid = 245036862 }}</ref> When higher doses of salicylate are ingested (more than 4 g), the half-life becomes much longer (15 h to 30 h),<ref name="Chyka2007">{{cite journal | vauthors = 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
==History==
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In 1853, chemist [[Charles Frédéric Gerhardt]] treated [[sodium salicylate]] with [[acetyl chloride]] to produce acetylsalicylic acid for the first time;<ref name=Jeffreys2008/>{{rp|46–48}} in the second half of the 19th century, other academic chemists established the compound's chemical structure and devised more efficient methods of synthesis. In 1897, scientists at the drug and dye firm [[Bayer]] began investigating acetylsalicylic acid as a less-irritating replacement for standard common salicylate medicines, and identified a new way to synthesize it.<ref name=Jeffreys2008/>{{rp|69–75}} By 1899, Bayer had dubbed this drug Aspirin and was selling it globally.<ref name=MannPlummer1991/>{{rp|27}} The word ''Aspirin'' was Bayer's brand name, rather than the generic name of the drug; however, Bayer's rights to the trademark were lost or sold in many countries. Aspirin's popularity grew over the first half of the 20th century leading to fierce competition with the proliferation of aspirin brands and products.<ref name=ACS/>
Aspirin's popularity declined after the development of [[paracetamol|acetaminophen/paracetamol]] in 1956 and [[ibuprofen]] in 1962. In the 1960s and 1970s, [[John Vane]] and others discovered the basic mechanism of aspirin's effects,<ref name=Jeffreys2008/>{{rp|226–231}} 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.<ref name=Jeffreys2008/>{{rp|247–257}} The initial large studies on the use of low-dose aspirin to prevent heart attacks that were published in the 1970s and 1980s helped spur reform in [[clinical research ethics]] and [[guidelines for human subject research]] and US federal law, and are often cited as examples of clinical trials that included only men, but from which people drew general conclusions that did not hold true for women.<ref>{{cite journal | vauthors = Schiebinger L | title = Women's health and clinical trials | journal = The Journal of Clinical Investigation | volume = 112 | issue = 7 | pages = 973–7 | date = October 2003 | pmid = 14523031 | pmc = 198535 | doi = 10.1172/JCI19993 }}</ref><ref>{{cite journal | vauthors = | title = Regular aspirin intake and acute myocardial infarction | journal = British Medical Journal | volume = 1 | issue = 5905 | pages = 440–3 | date = March 1974 | pmid = 4816857 | pmc = 1633212 | doi = 10.1136/bmj.1.5905.440 }}</ref><ref>{{cite journal | vauthors = Elwood PC, Cochrane AL, Burr ML, Sweetnam PM, Williams G, Welsby E, Hughes SJ, Renton R
Aspirin sales revived considerably in the last decades of the 20th century, and remain strong in the 21st century with widespread use as a preventive treatment for [[heart attack]]s and [[stroke]]s.<ref name=Jeffreys2008/>{{rp|267–269}}
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| caption2 = In the US., "aspirin" is a generic name.
}}
Bayer lost its trademark for Aspirin in the United States and some other countries in actions taken between 1918 and 1921 because it had failed to use the name for its own product correctly and had for years allowed the use of "Aspirin" by other manufacturers without defending the intellectual property rights.<ref>{{cite court |litigants=Bayer Co. v. United Drug Co. |vol=272 |reporter=F. |opinion=505 |pinpoint=p.512 |court=S.D.N.Y |date=1921 |url=https://cyber.law.harvard.edu/metaschool/fisher/domain/tmcases/bayer.htm }}</ref> Today, aspirin is a [[generic trademark]] in many countries.<ref>{{cite web |url= https://www.genericides.org/trademark/aspirin |title= Has aspirin become a generic trademark? |access-date= 17 February 2021 |website= genericides.org |date= 25 March 2020 |archive-date= 5 March 2021 |archive-url= https://web.archive.org/web/20210305221908/https://genericides.org/trademark/aspirin |url-status= dead }}</ref><ref>{{
===Compendial status===
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==Medical use==
Aspirin is used in the treatment of a number of conditions, including fever, pain, [[rheumatic fever]], and inflammatory conditions, such as [[rheumatoid arthritis]], [[pericarditis]], and [[Kawasaki disease]].<ref name=AHFS/> Lower doses of aspirin have also been shown to reduce the risk of death from a [[myocardial infarction|heart attack]], or the risk of [[stroke]] in people who are at high risk or who have cardiovascular disease, but not in elderly people who are otherwise healthy.<ref name="USFDA-patient-guideline">{{citation-attribution|1={{cite web |title=Aspirin for reducing your risk of heart attack and stroke: know the facts |url=https://www.fda.gov/drugs/safe-daily-use-aspirin/aspirin-reducing-your-risk-heart-attack-and-stroke-know-facts |publisher=U.S. [[Food and Drug Administration]] (FDA) |access-date=26 July 2012 |url-status=live |archive-url=https://web.archive.org/web/20120814182151/https://www.fda.gov/Drugs/ResourcesForYou/Consumers/BuyingUsingMedicineSafely/UnderstandingOver-the-CounterMedicines/SafeDailyUseofAspirin/ucm291433.htm |archive-date=14 August 2012}} }}</ref><ref name="USPSTF-CV">{{citation-attribution|1={{cite web |title=Aspirin for the prevention of cardiovascular disease |url=http://www.uspreventiveservicestaskforce.org/uspstf/uspsasmi.htm |publisher=[[U.S. Preventive Services Task Force]] |access-date=26 July 2012 |url-status=dead |archive-url=https://web.archive.org/web/20120711031337/http://www.uspreventiveservicestaskforce.org/uspstf/uspsasmi.htm |archive-date=11 July 2012}} }}</ref><ref>{{cite journal | vauthors = Seshasai SR, Wijesuriya S, Sivakumaran R, Nethercott S, Erqou S, Sattar N, Ray KK
===Pain===
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===Inflammation===
Aspirin is used as an [[anti-inflammatory agent]] for both acute and long-term [[inflammation]],<ref name="pmid19597002">{{cite journal | vauthors = Morris T, Stables M, Hobbs A, de Souza P, Colville-Nash P, Warner T, Newson J, Bellingan G, Gilroy DW
===Heart attacks and strokes===
Aspirin is an important part of the treatment of those who have had a [[myocardial infarction|heart attack]].<ref>{{cite book | title = Myocardial infarction with ST-segment elevation: the acute management of myocardial infarction with ST-segment elevation [Internet] | series = NICE Clinical Guidelines | issue = 167 | date = July 2013 | pmid = 25340241 | chapter-url = https://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0071000/ | url-status = live | archive-url = https://web.archive.org/web/20151231192814/http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0071000/ | archive-date = 31 December 2015 | at = 17.2 Aspirin | author1 = National Clinical Guideline Centre (UK) | chapter = Adjunctive pharmacotherapy and associated NICE guidance | publisher = Royal College of Physicians (UK) }}</ref> It is generally not recommended for routine use by people with no other health problems, including those over the age of 70.<ref name="Arnett-2019">{{cite journal | vauthors = Arnett DK, Blumenthal RS, Albert MA, Buroker AB, Goldberger ZD, Hahn EJ, Himmelfarb CD, Khera A, Lloyd-Jones D, McEvoy JW, Michos ED, Miedema MD, Muñoz D, Smith SC, Virani SS, Williams KA, Yeboah J, Ziaeian B
The 2009 Antithrombotic Trialists' Collaboration published in Lancet evaluated the efficacy and safety of low dose aspirin in secondary prevention. In those with prior ischaemic stroke or acute myocardial infarction, daily low dose aspirin was associated with a 19% relative risk reduction of serious cardiovascular events (non-fatal myocardial infarction, non-fatal stroke, or vascular death). This did come at the expense of a 0.19% absolute risk increase in gastrointestinal bleeding; however, the benefits outweigh the hazard risk in this case.{{citation needed|date=April 2023}} Data from previous trials have suggested that weight-based dosing of aspirin has greater benefits in primary prevention of cardiovascular outcomes.<ref name="Lancet2018Dose"/> However, more recent trials were not able to replicate similar outcomes using low dose aspirin in low body weight (<70 kg) in specific subset of population studied i.e. elderly and diabetic population, and more evidence is required to study the effect of high dose aspirin in high body weight (≥70 kg).<ref>{{cite journal | vauthors = Bowman L, Mafham M, Wallendszus K, Stevens W, Buck G, Barton J, Murphy K, Aung T, Haynes R, Cox J, Murawska A, Young A, Lay M, Chen F, Sammons E, Waters E, Adler A, Bodansky J, Farmer A, McPherson R, Neil A, Simpson D, Peto R, Baigent C, Collins R, Parish S, Armitage J
After [[percutaneous coronary intervention]]s (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.<ref>{{cite web | author = National Guideline Clearinghouse (NGC) |title=2011 ACCF/AHA/SCAI guideline for percutaneous coronary artery intervention. A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions |url=http://www.guideline.gov/content.aspx?id=34980 |url-status=dead |archive-url=https://web.archive.org/web/20120813064712/http://www.guideline.gov/content.aspx?id=34980 |archive-date=13 August 2012 |access-date=28 August 2012 |publisher=United States [[Agency for Healthcare Research and Quality]] (AHRQ)}}</ref> Frequently, aspirin is combined with an [[ADP receptor inhibitor]], such as [[clopidogrel]], [[prasugrel]], or [[ticagrelor]] to prevent [[Thrombosis|blood clots]]. This is called dual antiplatelet therapy (DAPT). Duration of DAPT was advised in the United States and European Union guidelines after the CURE<ref>{{cite journal |vauthors=Yusuf S, Zhao F, Mehta SR, Chrolavicius S, Tognoni G, Fox KK |date=August 2001 |title=Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation |url=http://real.mtak.hu/12922/1/1277670.pdf |journal=The New England Journal of Medicine |volume=345 |issue=7 |pages=494–502 |doi=10.1056/nejmoa010746 |pmid=11519503|s2cid=15459216 }}</ref> and PRODIGY<ref>{{cite journal
The status of the use of aspirin for the primary prevention in cardiovascular disease is conflicting and inconsistent, with recent changes from previously recommending it widely decades ago, and that some referenced newer trials in clinical guidelines show less of benefit of adding aspirin alongside other anti-hypertensive and cholesterol lowering therapies.<ref name="Arnett-2019" /><ref name="Visseren-2021">{{cite journal | vauthors = Visseren FL, Mach F, Smulders YM, Carballo D, Koskinas KC, Bäck M, Benetos A, Biffi A, Boavida JM, Capodanno D, Cosyns B, Crawford C, Davos CH, Desormais I, Di Angelantonio E, Franco OH, Halvorsen S, Hobbs FD, Hollander M, Jankowska EA, Michal M, Sacco S, Sattar N, Tokgozoglu L, Tonstad S, Tsioufis KP, van Dis I, van Gelder IC, Wanner C, Williams B
As of {{as of|2022|April|lc=n|alt=|bare=yes}}, the [[United States Preventive Services Task Force]] (USPSTF) determined that there was a "small net benefit" for patients aged 40–59 with a 10% or greater 10-year cardiovascular disease (CVD) risk, and "no net benefit" for patients aged over 60.<ref>{{citation-attribution|{{cite web | title=Recommendation: Aspirin Use to Prevent Cardiovascular Disease: Preventive Medication | website=United States Preventive Services Taskforce | date=23 November 2020 | url=https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/aspirin-to-prevent-cardiovascular-disease-preventive-medication | access-date=5 May 2022}}}}</ref><ref>{{cite journal | vauthors = Davidson KW, Barry MJ, Mangione CM, Cabana M, Chelmow D, Coker TR, Davis EM, Donahue KE, Jaén CR, Krist AH, Kubik M, Li L, Ogedegbe G, Pbert L, Ruiz JM, Stevermer J, Tseng CW, Wong JB
===Cancer prevention===
Aspirin may reduce the overall risk of both getting cancer and dying from cancer.<ref name=Cuz2014>{{cite journal | vauthors = Cuzick J, Thorat MA, Bosetti C, Brown PH, Burn J, Cook NR, Ford LG, Jacobs EJ, Jankowski JA, La Vecchia C, Law M, Meyskens F, Rothwell PM, Senn HJ, Umar A
Some conclude the benefits are greater than the risks due to bleeding in those at average risk.<ref name=Cuz2014/> Others are unclear if the benefits are greater than the risk.<ref>{{cite journal
* {{lay source|template=cite web|url=https://annals.org/aim/fullarticle/2513180/aspirin-use-primary-prevention-cardiovascular-disease-colorectal-cancer-recommendations-from|title=Who developed these recommendations?|date=21 June 2016|website=Annals of Internal Medicine}}</ref>
A meta-analysis through 2019 said that there was an association between taking aspirin and lower risk of cancer of the colorectum, esophagus, and stomach.<ref>{{cite journal | vauthors = Bosetti C, Santucci C, Gallus S, Martinetti M, La Vecchia C | title = Aspirin and the risk of colorectal and other digestive tract cancers: an updated meta-analysis through 2019 | journal = Annals of Oncology | volume = 31 | issue = 5 | pages = 558–568 | date = May 2020 | pmid = 32272209 | doi = 10.1016/j.annonc.2020.02.012 | quote = The present comprehensive meta-analysis supports and further quantifies the inverse association between regular aspirin use and the risk of colorectal and other digestive tract cancers, including some rare ones. The favorable effect of aspirin increases with longer duration of use, and, for colorectal cancer, with increasing dose. | doi-access = free | title-link = doi | hdl = 2434/730600 | hdl-access = free }}</ref>
In 2021, the U.S. Preventive services Task Force raised questions about the use of aspirin in cancer prevention. It notes the results of the 2018 ASPREE (Aspirin in Reducing Events in the Elderly) Trial, in which the risk of cancer-related death was higher in the aspirin-treated group than in the placebo group.<ref>{{cite journal | vauthors = McNeil JJ, Nelson MR, Woods RL, Lockery JE, Wolfe R, Reid CM, Kirpach B, Shah RC, Ives DG, Storey E, Ryan J, Tonkin AM, Newman AB, Williamson JD, Margolis KL, Ernst ME, Abhayaratna WP, Stocks N, Fitzgerald SM, Orchard SG, Trevaks RE, Beilin LJ, Donnan GA, Gibbs P, Johnston CI, Radziszewska B, Grimm R, Murray AM
===Psychiatry===
====Bipolar disorder====
Aspirin, along with several other agents with anti-inflammatory properties, has been repurposed as an add-on treatment for depressive episodes in subjects with [[bipolar disorder]] in light of the possible role of inflammation in the pathogenesis of severe mental disorders.<ref name="repurposed2021">{{cite journal | vauthors = Bartoli F, Cavaleri D, Bachi B, Moretti F, Riboldi I, Crocamo C, Carrà G | title = Repurposed drugs as adjunctive treatments for mania and bipolar depression: A meta-review and critical appraisal of meta-analyses of randomized placebo-controlled trials | journal = Journal of Psychiatric Research | volume = 143 | pages = 230–238 | date = November 2021 | pmid = 34509090 | doi = 10.1016/j.jpsychires.2021.09.018 | s2cid = 237485915 }}</ref> A 2022 systematic review concluded that aspirin exposure reduced the risk of depression in a pooled cohort of three studies (HR 0.624, 95% CI: 0.0503, 1.198, P=0.033). However, further high-quality, longer-duration, double-blind randomized controlled trials (RCTs) are needed to determine whether aspirin is an effective add-on treatment for bipolar depression.<ref>{{cite journal | vauthors = Dominiak M, Gędek A, Sikorska M, Mierzejewski P, Wojnar M, Antosik-Wójcińska AZ | title = Acetylsalicylic Acid and Mood Disorders: A Systematic Review | journal = Pharmaceuticals | volume = 16 | issue = 1 | pages = 67 | date = December 2022 | pmid = 36678565 | pmc = 9861965 | doi = 10.3390/ph16010067 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Savitz JB, Teague TK, Misaki M, Macaluso M, Wurfel BE, Meyer M, Drevets D, Yates W, Gleason O, Drevets WC, Preskorn SH
====Dementia====
Although cohort and longitudinal studies have shown low-dose aspirin has a greater likelihood of reducing the incidence of dementia, numerous randomized controlled trials have not validated this.<ref>{{cite journal | vauthors = Li H, Li W, Zhang X, Ma XC, Zhang RW | title = Aspirin Use on Incident Dementia and Mild Cognitive Decline: A Systematic Review and Meta-Analysis | journal = Frontiers in Aging Neuroscience | volume = 12 | pages = 578071 | date = 4 February 2021
==== Schizophrenia ====
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===Other uses===
Aspirin is a first-line treatment for the fever and joint-pain symptoms of [[rheumatic fever|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.<ref name=NHFA>{{cite web |url=http://www.racgp.org.au/Content/NavigationMenu/ClinicalResources/RACGPGuidelines/DiagnosisandmanagementofacuterheumaticfeverandrheumaticheartdiseaseinAustralia/NHFA-CSANZ_ARF_RHD_2006.pdf |archive-url=https://web.archive.org/web/20080726052030/http://www.racgp.org.au/Content/NavigationMenu/ClinicalResources/RACGPGuidelines/DiagnosisandmanagementofacuterheumaticfeverandrheumaticheartdiseaseinAustralia/NHFA-CSANZ_ARF_RHD_2006.pdf |archive-date=26 July 2008 |title=Diagnosis and management of acute rheumatic fever and rheumatic heart disease in Australia. An evidence-based review |author=[[National Heart Foundation of Australia]] (RF/RHD guideline development working group) and the Cardiac Society of Australia and New Zealand |year=2006 |publisher=National Heart Foundation of Australia |pages=33–37}}</ref><ref>{{cite journal | vauthors = Saxena A, Kumar RK, Gera RP, Radhakrishnan S, Mishra S, Ahmed Z | title = Consensus guidelines on pediatric acute rheumatic fever and rheumatic heart disease | journal = Indian Pediatrics | volume = 45 | issue = 7 | pages = 565–73 | date = July 2008 | pmid = 18695275 }}</ref> [[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.<ref name=NHFA/><ref>{{cite journal | vauthors = Hashkes PJ, Tauber T, Somekh E, Brik R, Barash J, Mukamel M, Harel L, Lorber A, Berkovitch M, Uziel Y
Along with rheumatic fever, [[Kawasaki disease]] remains one of the few indications for aspirin use in children<ref>{{cite journal | vauthors = Rowley AH, Shulman ST | title = Pathogenesis and management of Kawasaki disease | journal = Expert Review of Anti-Infective Therapy | volume = 8 | issue = 2 | pages = 197–203 | date = February 2010 | pmid = 20109049 | pmc = 2845298 | doi = 10.1586/eri.09.109 }}</ref> in spite of a lack of high quality evidence for its effectiveness.<ref>{{cite journal | vauthors = Baumer JH, Love SJ, Gupta A, Haines LC, Maconochie I, Dua JS | title = Salicylate for the treatment of Kawasaki disease in children | journal = The Cochrane Database of Systematic Reviews | issue = 4 | pages = CD004175 | date = October 2006 | volume = 2010 | pmid = 17054199 | doi = 10.1002/14651858.CD004175.pub2 | pmc = 8765111 }}</ref>
Low-dose aspirin supplementation has moderate benefits when used for prevention of [[pre-eclampsia]].<ref>{{cite journal | vauthors = Duley L, Meher S, Hunter KE, Seidler AL, Askie LM | title = Antiplatelet agents for preventing pre-eclampsia and its complications | journal = The Cochrane Database of Systematic Reviews | volume = 2019 | issue = 10 | date = October 2019 | pmid = 31684684 | pmc = 6820858 | doi = 10.1002/14651858.CD004659.pub3 }}</ref><ref name=Roberge_2012>{{cite journal | vauthors = Roberge S, Villa P, Nicolaides K, Giguère Y, Vainio M, Bakthi A, Ebrashy A, Bujold E
Aspirin has also demonstrated [[Treatment of cancer|anti-tumoral]] effects, via inhibition of the [[PTTG1]] gene, which is often overexpressed in tumors.<ref>{{cite journal|title=Aspirin Mediates Its Antitumoral Effect Through Inhibiting PTTG1 in Pituitary Adenoma|doi=10.1210/clinem/dgac496|doi-access=free|journal=[[The Journal of Clinical Endocrinology and Metabolism]]
===Resistance===
{{see also|Drug tolerance}}
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,<ref>{{cite journal | vauthors = Dorsch MP, Lee JS, Lynch DR, Dunn SP, Rodgers JE, Schwartz T, Colby E, Montague D, Smyth SS
A study in 100 Italian people found, of the apparent 31% aspirin-resistant subjects, only 5% were truly resistant, and the others were [[Compliance (medicine)|noncompliant]].<ref name="pmid18680540">{{cite journal | vauthors = Pignatelli P, Di Santo S, Barillà F, Gaudio C, Violi F | title = Multiple anti-atherosclerotic treatments impair aspirin compliance: effects on aspirin resistance | journal = Journal of Thrombosis and Haemostasis | volume = 6 | issue = 10 | pages = 1832–4 | date = October 2008 | pmid = 18680540 | doi = 10.1111/j.1538-7836.2008.03122.x | s2cid = 1776526 | doi-access = free | title-link = doi }}</ref>
Another study of 400 healthy volunteers found no subjects who were truly resistant, but some had "pseudoresistance, reflecting delayed and reduced drug absorption".
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*{{lay source |template = cite news|vauthors = Thomas K|url= https://www.nytimes.com/2012/12/05/business/coating-on-buffered-aspirin-may-hide-its-heart-protective-effects.html|title = Study Raises Questions on Coating of Aspirin|date = 4 December 2012|website = [[The New York Times]] }}</ref>
Meta-analysis and systematic reviews have concluded that laboratory confirmed aspirin resistance confers increased rates of poorer outcomes in cardiovascular and neurovascular diseases.<ref>{{cite journal | vauthors = Li J, Song M, Jian Z, Guo W, Chen G, Jiang G, Wang J, Wu X, Huang L
== Dosages ==
Adult aspirin tablets are produced in standardised sizes, which vary slightly from country to country, for example 300{{nbsp}}mg in Britain and 325{{nbsp}}mg in the United States. Smaller doses are based on these standards, ''e.g.'', 75{{nbsp}}mg and 81{{nbsp}}mg tablets. The 81 mg tablets are commonly called "baby aspirin" or "baby-strength", because they were originally{{snd}}[[Reye syndrome|but no longer]]{{snd}}intended to be administered to infants and children.<ref>{{
In general, for adults, doses are taken four times a day for fever or arthritis,<ref name=BNF>{{
March 2009 recommendations from the USPSTF 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 bleeding|gastrointestinal hemorrhage]].<ref name="USPSTF 2009">{{cite journal | vauthors = ((US Preventive Services Task Force)) | title = Aspirin for the prevention of cardiovascular disease: U.S. Preventive Services Task Force recommendation statement | journal = Annals of Internal Medicine | volume = 150 | issue = 6 | pages = 396–404 | date = March 2009 | pmid = 19293072 | doi = 10.7326/0003-4819-150-6-200903170-00008 | doi-access = free | title-link = doi }}</ref><ref name=medscape>{{cite news|url=http://cme.medscape.com/viewarticle/589895 |title=Aspirin: more evidence that low dose is all that is needed |newspaper=Medscape |publisher=Medscape CME |access-date=11 May 2011}}</ref>{{update inline|date=October 2019}} The WHI study of postmenopausal women found that aspirin resulted in a 25% lower risk of death from cardiovascular disease and a 14% lower risk of death from any cause, though there was no significant difference between 81{{nbsp}}mg and 325{{nbsp}}mg aspirin doses.<ref>{{cite journal | vauthors = Berger JS, Brown DL, Burke GL, Oberman A, Kostis JB, Langer RD, Wong ND, Wassertheil-Smoller S
Low-dose aspirin use was also associated with a trend toward lower risk of cardiovascular events, and lower aspirin doses (75 or 81{{nbsp}}mg/day) may optimize efficacy and safety for people requiring aspirin for long-term prevention.<ref name="medscape" />
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.<ref>{{
==Adverse effects==
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<!-- Note that Contraindications is spelled correctly! It does not need to be changed. -->
Aspirin should not be taken by people who are allergic to [[ibuprofen]] or [[naproxen]],<ref name="drugs.com" /><ref name="personalmd">{{cite web |url=http://www.personalmd.com/drgdb/3.htm |archive-url=https://web.archive.org/web/20000918231717/http://personalmd.com/drgdb/3.htm |url-status=dead |archive-date=18 September 2000 |title=Oral Aspirin information |access-date=8 May 2008 |publisher=First DataBank }}</ref> or who have [[salicylate intolerance]]<ref name="pmid16247191">{{cite journal | vauthors = Raithel M, Baenkler HW, Naegel A, Buchwald F, Schultis HW, Backhaus B, Kimpel S, Koch H, Mach K, Hahn EG, Konturek PC
===Gastrointestinal===
Aspirin increases the risk of [[upper gastrointestinal bleeding]].<ref name="Sorensen 2000">{{cite journal | vauthors = Sørensen HT, Mellemkjaer L, Blot WJ, Nielsen GL, Steffensen FH, McLaughlin JK, Olsen JH | title = Risk of upper gastrointestinal bleeding associated with use of low-dose aspirin | journal = The American Journal of Gastroenterology | volume = 95 | issue = 9 | pages = 2218–2224 | date = September 2000 | pmid = 11007221 | doi = 10.1016/s0002-9270(00)01040-6 }}</ref> Enteric coating on aspirin
Blockade of COX-1 by aspirin apparently results in the upregulation of COX-2 as part of a gastric defense.<ref>{{cite journal |vauthors = Wallace JL |title = Prostaglandins, NSAIDs, and gastric mucosal protection: why doesn't the stomach digest itself? |journal = Physiological Reviews |volume = 88 |issue = 4 |pages = 1547–65 |date = October 2008 |pmid = 18923189 |doi = 10.1152/physrev.00004.2008 |s2cid = 448875 }}</ref>
"[[Buffer solution|Buffering]]" is an additional method
Taking
===Retinal vein occlusion===
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===Skin===
For a small number of people, taking aspirin can result in symptoms including [[hives]], swelling, and headache.<ref>{{
Aspirin and other NSAIDs, such as ibuprofen, may delay the healing of skin wounds.<ref>{{cite journal |vauthors=Stadelmann WK, Digenis AG, Tobin GR |title=Impediments to wound healing |journal=American Journal of Surgery |volume=176 |issue=2A Suppl |pages=39S–47S |date=August 1998 |pmid=9777971 |doi=10.1016/S0002-9610(98)00184-6}}</ref> Earlier findings from two small, low-quality trials suggested a benefit with aspirin (alongside compression therapy) on venous leg ulcer healing time and leg ulcer size,<ref>{{cite journal |vauthors=Layton AM, Ibbotson SH, Davies JA, Goodfield MJ |title=Randomised trial of oral aspirin for chronic venous leg ulcers |journal=Lancet |volume=344 |issue=8916 |pages=164–5 |date=July 1994 |pmid=7912767 |doi=10.1016/s0140-6736(94)92759-6 |s2cid=912169}}</ref><ref>{{cite journal |vauthors=del Río Solá ML, Antonio J, Fajardo G, Vaquero Puerta C |title=Influence of aspirin therapy in the ulcer associated with chronic venous insufficiency |journal=Annals of Vascular Surgery |volume=26 |issue=5 |pages=620–9 |date=July 2012 |pmid=22437068 |doi=10.1016/j.avsg.2011.02.051 | hdl=10324/2904 |hdl-access=free }}</ref><ref>{{cite journal |vauthors=de Oliveira Carvalho PE, Magolbo NG, De Aquino RF, Weller CD |title=Oral aspirin for treating venous leg ulcers |journal=The Cochrane Database of Systematic Reviews |volume=2016 |pages=CD009432 |date=February 2016 |issue=2 |pmid=26889740 |doi=10.1002/14651858.CD009432.pub2 |pmc=8627253 |collaboration=Cochrane Wounds Group}}</ref> however larger, more recent studies of higher quality have been unable to corroborate these outcomes.<ref>{{cite journal |vauthors=Jull A, Wadham A, Bullen C, Parag V, Kerse N, Waters J |title=Low dose aspirin as adjuvant treatment for venous leg ulceration: pragmatic, randomised, double blind, placebo controlled trial (Aspirin4VLU) |journal=BMJ |volume=359 |pages=j5157 |date=November 2017 |pmid=29175902 |pmc=5701114 |doi=10.1136/bmj.j5157}}</ref><ref>{{cite journal
===Other adverse effects===
Aspirin can induce [[angioedema|swelling of skin tissues]] in some people. In one study, [[angioedema]] appeared one to six hours after ingesting aspirin in some of the people. However, when the aspirin was taken alone, it did not cause angioedema in these people; the aspirin had been taken in combination with another NSAID-induced drug when angioedema appeared.<ref>{{cite journal |vauthors = Berges-Gimeno MP, Stevenson DD |title = Nonsteroidal anti-inflammatory drug-induced reactions and desensitization |journal = The Journal of Asthma |volume = 41 |issue = 4 |pages = 375–84 |date = June 2004 |pmid = 15281324 |doi = 10.1081/JAS-120037650 |s2cid = 29909460 }}</ref>
Aspirin causes an increased risk of cerebral microbleeds, having the appearance on [[MRI]] scans of 5 to 10{{nbsp}}mm or smaller, hypointense (dark holes) patches.<ref>{{cite journal |vauthors = Vernooij MW, Haag MD, van der Lugt A, Hofman A, Krestin GP, Stricker BH, Breteler MM
A study of a group with a mean dosage of aspirin of 270{{nbsp}}mg per day estimated an average absolute risk increase in [[intracerebral hemorrhage]] (ICH) of 12 events per 10,000 persons.<ref name=He1998/> 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.<ref name=He1998>{{cite journal |vauthors = He J, Whelton PK, Vu B, Klag MJ |title = Aspirin and risk of hemorrhagic stroke: a meta-analysis of randomized controlled trials |journal = JAMA |volume = 280 |issue = 22 |pages = 1930–5 |date = December 1998 |pmid = 9851479 |doi = 10.1001/jama.280.22.1930 |s2cid = 22997730 }}</ref> In cases where ICH already has occurred, aspirin use results in higher mortality, with a dose of about 250{{nbsp}}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).<ref name=Saloheimo2006>{{cite journal |vauthors = Saloheimo P, Ahonen M, Juvela S, Pyhtinen J, Savolainen ER, Hillbom M |title = Regular aspirin-use preceding the onset of primary intracerebral hemorrhage is an independent predictor for death |journal = Stroke |volume = 37 |issue = 1 |pages = 129–33 |date = January 2006 |pmid = 16322483 |doi = 10.1161/01.STR.0000196991.03618.31 |doi-access = free | title-link = doi }}</ref>
Aspirin and other NSAIDs can cause [[hyperkalemia|abnormally high blood levels of potassium]] by inducing a [[hyporeninemic hypoaldosteronism|hyporeninemic
Use of low-dose aspirin before a surgical procedure has been associated with an increased risk of bleeding events in some patients, however, ceasing aspirin prior to surgery has also been associated with an increase in major adverse cardiac events. An analysis of multiple studies found a three-fold increase in adverse events such as [[myocardial infarction]] in patients who ceased aspirin prior to surgery. The analysis found that the risk is dependent on the type of surgery being performed and the patient indication for aspirin use.<ref>{{cite journal | vauthors = Biondi-Zoccai GG, Lotrionte M, Agostoni P, Abbate A, Fusaro M, Burzotta F, Testa L, Sheiban I, Sangiorgi G
On 9 July 2015, the US [[Food and Drug Administration]] (FDA) toughened warnings of increased [[heart attack]] and [[stroke]] risk associated with [[nonsteroidal anti-inflammatory drug]]s (NSAID).<ref name="FDA-20150709" /> Aspirin is an NSAID but is not affected by the new warnings.<ref name="FDA-20150709">{{cite web |title=FDA strengthens warning of heart attack and stroke risk for non-steroidal anti-inflammatory drugs |url=https://www.fda.gov/consumers/consumer-updates/fda-strengthens-warning-heart-attack-and-stroke-risk-non-steroidal-anti-inflammatory-drugs |date=9 July 2015 |work=U.S. [[Food and Drug Administration]] (FDA) |access-date=9 July 2015 |url-status=live |archive-url=https://web.archive.org/web/20150711004922/https://www.fda.gov/ForConsumers/ConsumerUpdates/ucm453610.htm |archive-date=11 July 2015}}</ref>
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===Overdose===
{{Main|Aspirin poisoning}}
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%;<ref>{{cite web |vauthors = Kreplick LW |year=2001 |title=Salicylate toxicity in emergency medicine |publisher=[[Medscape]] |url=http://misc.medscape.com/pi/android/medscapeapp/html/A818242-business.html |url-status=live |archive-url=https://web.archive.org/web/20120831184805/http://misc.medscape.com/pi/android/medscapeapp/html/A818242-business.html |archive-date=31 August 2012}}</ref> chronic overdose may be especially severe in children.<ref name="Pediatrics1982-gaudreault">{{cite journal |vauthors = Gaudreault P, Temple AR, Lovejoy FH |title = The relative severity of acute versus chronic salicylate poisoning in children: a clinical comparison |journal = Pediatrics |volume = 70 |issue = 4 |pages = 566–9 |date = October 1982 |doi = 10.1542/peds.70.4.566 |pmid = 7122154 |s2cid = 12738659 }} (primary source)</ref> Toxicity is managed with a number of potential treatments, including [[activated charcoal]], intravenous dextrose and normal saline, [[sodium bicarbonate]], and [[Kidney dialysis|dialysis]].<ref>{{
=== Interactions ===
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==Research==
The ISIS-2 trial demonstrated that aspirin at doses of 160{{nbsp}}mg daily for one month, decreased the mortality by 21% of participants with a suspected myocardial infarction in the first five weeks.<ref name="The Lancet-1988">{{cite journal |date=August 1988 |journal=The Lancet |volume=332 |issue=8607 |pages=349–360 |doi=10.1016/s0140-6736(88)92833-4 |issn=0140-6736|title=Randomised Trial of Intravenous Streptokinase, Oral Aspirin, Both, or Neither Among 17,187 Cases of Suspected Acute Myocardial Infarction: Isis-2 |s2cid=21071664 | pmid = 2899772 }}</ref> A single daily dose of 324{{nbsp}}mg of aspirin for 12 weeks has a highly protective effect against acute myocardial infarction and death in men with unstable angina.<ref name="Lewis-1983">{{cite journal | vauthors = Lewis HD, Davis JW, Archibald DG, Steinke WE, Smitherman TC, Doherty JE, Schnaper HW, LeWinter MM, Linares E, Pouget JM, Sabharwal SC, Chesler E, DeMots H
=== Bipolar disorder ===
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===Infectious diseases===
Several studies investigated the anti-infective properties of aspirin for bacterial, viral and parasitic infections. Aspirin was demonstrated to limit platelet activation induced by ''Staphylococcus aureus'' and ''Enterococcus faecalis'' and to reduce streptococcal adhesion to heart valves. In patients with tuberculous meningitis, the addition of aspirin reduced the risk of new cerebral infarction [RR = 0.52 (0.29-0.92)]. A role of aspirin on bacterial and fungal biofilm is also being supported by growing evidence.<ref>{{cite journal| vauthors = Di Bella S, Luzzati R, Principe L, Zerbato V, Meroni E, Giuffrè M, Crocè LS, Merlo M, Perotto M, Dolso E, Maurel C
===Cancer prevention===
Evidence from observational studies were conflicting on the effect of aspirin in breast cancer prevention,<ref>{{cite journal | vauthors = Cao Y, Tan A | title = Aspirin might reduce the incidence of breast cancer: An updated meta-analysis of 38 observational studies | journal = Medicine | volume = 99 | issue = 38 | pages = e21917 | date = September 2020 | pmid = 32957311 | doi = 10.1097/md.0000000000021917 | pmc = 7505405 }}</ref> a randomized controlled trial showed that aspirin had no significant effect in reducing breast cancer <ref>{{cite journal | vauthors = Cook NR, Lee IM, Gaziano JM, Gordon D, Ridker PM, Manson JE, Hennekens CH, Buring JE
=== In gardening ===
There are
== Veterinary medicine ==
Aspirin is sometimes used in veterinary medicine as an [[anticoagulant]] or to [[analgesic|relieve pain]] associated with musculoskeletal inflammation or [[osteoarthritis]]. Aspirin should only be given to animals under the direct supervision of a [[veterinarian]], as adverse effects—including gastrointestinal issues—are common. An aspirin overdose in any species may result in [[salicylate poisoning]], characterized by hemorrhaging, seizures, coma, and even death.<ref name="Edwards-2016">{{
Dogs are better able to tolerate aspirin than cats are.<ref name="Merck" /> Cats metabolize aspirin slowly because they lack the [[glucuronide]] conjugates that aid in the excretion of aspirin, making it potentially toxic if dosing is not spaced out properly.<ref name="Edwards-2016" /><ref>{{cite book|title=Feline internal medicine secrets|publisher=Hanley & Belfus|year=2001|isbn=978-1-56053-461-7 |veditors = Lappin MR |location=Philadelphia|page=160}}</ref> No clinical signs of toxicosis occurred when cats were given 25{{nbsp}}mg/kg of aspirin every 48 hours for 4 weeks,<ref name="Merck">{{cite web|url=http://www.merckmanuals.com/vet/toxicology/toxicities_from_human_drugs/analgesics_toxicity.html|title=Analgesics (toxicity) |publisher=Merck|archive-url= https://web.archive.org/web/20150411095033/http://www.merckmanuals.com/vet/toxicology/toxicities_from_human_drugs/analgesics_toxicity.html |archive-date=11 April 2015 |url-status=live|access-date=19 January 2018}}</ref> but the recommended dose for relief of pain and fever and for treating [[thrombophilia|blood clotting diseases]] in cats is 10{{nbsp}}mg/kg every 48 hours to allow for metabolization.<ref name="Edwards-2016" /><ref>{{cite web|url=http://www.ansci.cornell.edu/plants/toxcat/toxcat.html|title=Plants poisonous to livestock|publisher=Cornell University Department of Animal Science|archive-url=https://web.archive.org/web/20150816192109/http://www.ansci.cornell.edu/plants/toxcat/toxcat.html|archive-date=16 August 2015|url-status=live|access-date=3 March 2016}}</ref>
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