Editing Aspirin (section)

===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 may be used in manufacturing to prevent release of aspirin into the stomach to reduce gastric harm, but enteric coating does not reduce gastrointestinal bleeding risk.<ref name="Sorensen 2000" /><ref name="Kedir 2021">{{cite journal | vauthors = Kedir HM, Sisay EA, Abiye AA | title = Enteric-Coated Aspirin and the Risk of Gastrointestinal Side Effects: A Systematic Review | journal = International Journal of General Medicine | volume = 14 | pages = 4757–4763 | year = 2021 | pmid = 34466020 | doi = 10.2147/ijgm.s326929 | pmc = 8403009 | doi-access = free }}</ref> Enteric-coated aspirin may not be as effective at reducing blood clot risk.<ref>{{cite web | vauthors = Torborg L | title=Mayo Clinic Q and A: Coated aspirin may not be as effective at reducing blood clot risk | website=Mayo Clinic News Network | date=4 December 2018 | url=https://newsnetwork.mayoclinic.org/discussion/mayo-clinic-q-and-a-coated-aspirin-may-not-be-as-effective-at-reducing-blood-clot-risk/}}</ref><ref>{{cite journal | vauthors = Cox D, Maree AO, Dooley M, Conroy R, Byrne MF, Fitzgerald DJ | title = Effect of enteric coating on antiplatelet activity of low-dose aspirin in healthy volunteers | journal = Stroke | volume = 37 | issue = 8 | pages = 2153–2158 | date = August 2006 | pmid = 16794200 | doi = 10.1161/01.STR.0000231683.43347.ec | s2cid = 8034371 | doi-access = free }}</ref> Combining aspirin with other [[Nonsteroidal anti-inflammatory drug|NSAIDs]] has been shown to further increase the risk of gastrointestinal bleeding.<ref name="Sorensen 2000" /> Using aspirin in combination with clopidogrel or warfarin also increases the risk of upper gastrointestinal bleeding.<ref>{{cite journal | vauthors = Delaney JA, Opatrny L, Brophy JM, Suissa S | title = Drug drug interactions between antithrombotic medications and the risk of gastrointestinal bleeding | journal = CMAJ | volume = 177 | issue = 4 | pages = 347–351 | date = August 2007 | pmid = 17698822 | pmc = 1942107 | doi = 10.1503/cmaj.070186 }}</ref>

The 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> There is no clear evidence that simultaneous use of a COX-2 inhibitor with aspirin may increase the risk of gastrointestinal injury.<ref name="Rostom-2007">{{cite journal |vauthors = Rostom A, Muir K, Dubé C, Jolicoeur E, Boucher M, Joyce J, Tugwell P, Wells GW |title = Gastrointestinal safety of cyclooxygenase-2 inhibitors: a Cochrane Collaboration systematic review |journal = Clinical Gastroenterology and Hepatology |volume = 5 |issue = 7 |pages = 818–28, 828.e1-5; quiz 768 |date = July 2007 |pmid = 17556027 |doi = 10.1016/j.cgh.2007.03.011 |doi-access = free }}</ref>

"[[Buffer solution|Buffering]]" is an additional method used with the intent to mitigate gastrointestinal bleeding, such as by preventing aspirin from concentrating in the walls of the stomach, although the benefits of buffered aspirin are disputed.<ref name="Clerici_2023">{{cite journal | vauthors = Clerici B, Cattaneo M | title = Pharmacological Efficacy and Gastrointestinal Safety of Different Aspirin Formulations for Cardiovascular Prevention: A Narrative Review | journal = Journal of Cardiovascular Development and Disease | volume = 10 | issue = 4 | date = March 2023 | page = 137 | pmid = 37103016 | pmc = 10145431 | doi = 10.3390/jcdd10040137 | doi-access = free }}</ref> Almost any buffering agent used in antacids can be used; Bufferin, for example, uses [[magnesium oxide]]. Other preparations use [[calcium carbonate]].<ref>{{cite web |url=http://antoine.frostburg.edu/chem/senese/101/acidbase/faq/buffered-aspirin.shtml |title=General chemistry online: FAQ: Acids and bases: What is the buffer system in buffered aspirin? |publisher=Antoine.frostburg.edu |access-date=11 May 2011 |url-status=live |archive-url=https://web.archive.org/web/20110414145143/http://antoine.frostburg.edu/chem/senese/101/acidbase/faq/buffered-aspirin.shtml |archive-date=14 April 2011}}</ref> Gas-forming agents in [[effervescent tablet|effervescent tablet and powder]] formulations can also double as a buffering agent, one example being [[sodium bicarbonate]], used in [[Alka-Seltzer]].<ref>{{cite journal | vauthors = Davison C, Smith BW, Smith PK | title = Effects of buffered and unbuffered acetylsalicylic acid upon the gastric acidity of normal human subjects | journal = Journal of Pharmaceutical Sciences | volume = 51 | issue = 8 | pages = 759–763 | date = August 1962 | pmid = 13883982 | doi = 10.1002/jps.2600510813 }}</ref>

Taking vitamin C with aspirin has been investigated as a method of protecting the stomach lining. In trials, vitamin C-releasing aspirin (ASA-VitC) or a buffered aspirin formulation containing vitamin C was found to cause less stomach damage than aspirin alone.<ref name="Dammann">{{cite journal |vauthors = Dammann HG, Saleki M, Torz M, Schulz HU, Krupp S, Schürer M, Timm J, Gessner U |title = Effects of buffered and plain acetylsalicylic acid formulations with and without ascorbic acid on gastric mucosa in healthy subjects |journal = Alimentary Pharmacology & Therapeutics |volume = 19 |issue = 3 |pages = 367–74 |date = February 2004 |pmid = 14984384 |doi = 10.1111/j.1365-2036.2004.01742.x |s2cid = 22688422 |doi-access = free | title-link = doi }}</ref><ref name="Konturek">{{cite journal |vauthors = Konturek PC, Kania J, Hahn EG, Konturek JW |title = Ascorbic acid attenuates aspirin-induced gastric damage: role of inducible nitric oxide synthase |journal = Journal of Physiology and Pharmacology |volume = 57 |issue = Suppl 5 |pages = 125–36 |date = November 2006 |pmid = 17218764 }}</ref>