Aspirin

Aspirin
INN: acetylsalicylic acid
Aspirin-skeletal.svg
Aspirin-B-3D-balls.png
Clinical data
Pronunciationacetylsalicylic acid k/
Trade namesBayer Aspirin, many others
Synonyms2-acetoxybenzoic acid
acetylsalicylate
acetylsalicylic acid
O-acetylsalicylic acid, Aspirin (BAN UK), Aspirin (USAN US)
AHFS/Monograph
a682878
License data
Pregnancy
category
  • AU: C
  • US: C (Risk not ruled out) D in the 3rd trimester
Routes of
administration
by mouth, rectal, lysine acetylsalicylate may be given intravenously or intramuscularly
ATC code
Legal status
Legal status
  • AU: S2 (Pharmacy only) except when given intravenously (in which case it is schedule 4), used in animal medicine (schedule 5/6) or when the dose is higher than usual.
  • UK: General sales list (GSL, OTC)
  • US: OTC
Pharmacokinetic data
Bioavailability80–100%[2]
Protein binding80–90%[1]
MetabolismLiver, (CYP2C19 and possibly CYP3A), some is also hydrolysed to salicylate in the gut wall.[1]
half-lifeDose-dependent; 2 h to 3 h for low doses (100 mg or less), 15 h to 30 h for large doses.[1]
ExcretionUrine (80–100%), sweat, saliva, feces[2]
Identifiers
50-78-2 ☑Y
2244
4139
DB00945 ☑Y
2157 ☑Y
R16CO5Y76E
D00109 ☑Y
CHEBI:15365 ☑Y
CHEMBL25 ☑Y
PDB RCSB PDB)
100.000.059 Edit this at Wikidata
Chemical and physical data
FormulaC9H8O4
Molar mass180.158 g/mol[3]
3D model (Interactive image
Density1.40 g/cm3
Melting point136 °C (277 °F) [3]
Boiling point140 °C (284 °F) (decomposes)
Solubility in water3 mg/mL (20 °C)
  (verify)

Aspirin, also known as acetylsalicylic acid (ASA), is a medication used to treat pain, fever, or inflammation.[4] Specific inflammatory conditions in which aspirin is used include Kawasaki disease, pericarditis, and rheumatic fever.[4] Aspirin given shortly after a heart attack decreases the risk of death.[4] Aspirin is also used long-term to help prevent further heart attacks, ischaemic strokes, and blood clots in people at high risk.[4] It may also decrease the risk of certain types of cancer, particularly colorectal cancer.[5] For pain or fever, effects typically begin within 30 minutes.[4] Aspirin is a nonsteroidal anti-inflammatory drug (NSAID) and works similar to other NSAIDs but also suppresses the normal functioning of platelets.[4]

One common adverse effect is an upset stomach.[4] More significant side effects include stomach ulcers, stomach bleeding, and worsening asthma.[4] Bleeding risk is greater among those who are older, drink alcohol, take other NSAIDs, or are on other blood thinners.[4] Aspirin is not recommended in the last part of pregnancy.[4] It is not generally recommended in children with infections because of the risk of Reye syndrome.[4] High doses may result in ringing in the ears.[4]

A precursor to aspirin found in leaves from the willow tree has been used for its health effects for at least 2,400 years.[6][7] In 1853, chemist Charles Frédéric Gerhardt treated the medicine sodium salicylate with acetyl chloride to produce acetylsalicylic acid for the first time.[8] For the next fifty years, other chemists established the chemical structure and came up with more efficient methods to make it.[8]:69–75 In 1897, scientists at the Bayer company began studying acetylsalicylic acid as a less-irritating replacement medication for common salicylate medicines.[8]:69–75[9] By 1899, Bayer had named it "Aspirin" and sold it around the world.[10] Aspirin's popularity grew over the first half of the twentieth century leading to competition between many brands and formulations.[11] The word Aspirin was Bayer's brand name; however, their rights to the trademark were lost or sold in many countries.[11]

Aspirin is one of the most widely used medications globally, with an estimated 40,000 tonnes (44,000 tons) (50 to 120 billion pills) consumed each year.[6][12] It is on the World Health Organization's (WHO's) List of Essential Medicines, the safest and most effective medicines needed in a health system.[13] As of 2014 the wholesale cost in the developing world is $0.002 to $0.025 USD per dose.[14] As of 2015 the cost for a typical month of medication in the United States is less than $25.00 USD.[15] It is available as a generic medication.[4]

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.[16] Lower doses of aspirin have also been shown to reduce the risk of death from a 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.[17][18][19][20][21] There is some evidence that aspirin is effective at preventing colorectal cancer, though the mechanisms of this effect are unclear.[22] In the United States, low dose aspirin is deemed reasonable in those between 50 and 70 years old who have a more than 10% risk of cardiovascular disease, and are not at an increased risk of bleeding, and who are otherwise healthy.[23]

Pain

Aspirin 325 mg / 5 grains for pain
Uncoated aspirin tablets, consisting of about 90% acetylsalicylic acid, along with a minor amount of inert fillers and binders

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.[24] Aspirin is generally ineffective for those pains caused by muscle cramps, bloating, gastric distension, or acute skin irritation.[25] As with other NSAIDs, combinations of aspirin and caffeine provide slightly greater pain relief than aspirin alone.[26] Effervescent formulations of aspirin relieve pain faster than aspirin in tablets,[27] which makes them useful for the treatment of migraines.[28] Topical aspirin may be effective for treating some types of neuropathic pain.[29]

Headache

Aspirin, either by itself or in a combined formulation, effectively treats certain types of a 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.[30]

Aspirin, especially as a component of an aspirin/paracetamol/caffeine combination, 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.[31]

Fever

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.[32] 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.[33][34][35] 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.[36]

Inflammation

Aspirin is used as an anti-inflammatory agent for both acute and long-term inflammation,[37] as well as for treatment of inflammatory diseases, such as rheumatoid arthritis.[16]

Heart attacks and strokes

Aspirin is an important part of the treatment of those who have had a myocardial infarction (heart attack).[38]

High risk

For people who have already had a heart attack or stroke, taking aspirin daily for two years prevented 1 in 50 from having a cardiovascular problem (heart attack, stroke, or death), but also caused non-fatal bleeding problems to occur in 1 of 400 people.[39][40][41] Low dose aspirin appears useful for people less than 70 kg while higher dose aspirin is required to benefit those over 70 kg.[42]

Lower risk

In those with no previous history of heart disease, aspirin has been thought to decrease the risk of a non-fatal myocardial infarction but not to change the overall risk of death.[43] One study found that among those who have never had a heart attack or stroke, taking aspirin daily for 1 year prevents 1 in 1,667 from having a non-fatal heart attack or stroke, but caused 1 in 3,333 to have a non-fatal bleeding event. However, the study population were at relatively higher risk than those who had never had a heart attack or stroke.[44] A large trial from 2018 in healthy people who were at least 70 years old, found no difference in preventing cardiovascular events, but a higher risk of serious bleeding.[21]

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,[45][46] while others have suggested the risks of other events, such as gastrointestinal bleeding, were enough to outweigh any potential benefit, and recommended against using aspirin for primary prevention entirely.[47] Aspirin has also been suggested as a component of a polypill for prevention of cardiovascular disease.[48][49]

Complicating the use of aspirin for prevention is the phenomenon of aspirin resistance.[50][51] For people who are resistant, aspirin's efficacy is reduced.[52] Some authors have suggested testing regimens to identify people who are resistant to aspirin.[53]

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.[54] 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.[55] However, they agree that aspirin be continued indefinitely after DAPT is complete.

Cancer prevention

Aspirin is thought to reduce the overall risk of both getting cancer and dying from cancer.[56] This effect is particularly beneficial for colorectal cancer (CRC)[22][57][58][59] but must be taken for at least 10–20 years to see this benefit.[60] It may also slightly reduce the risk of endometrial cancer,[61] breast cancer, and prostate cancer.[62]

Some conclude the benefits are greater than the risks due to bleeding in those at average risk.[56] Others are unclear if the benefits are greater than the risk.[63][64] 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.[65] Nine years later however, the USPSTF issued a grade B recommendation for the use of low-dose aspirin (75 to 100 mg/day) “for the primary prevention of CVD [cardiovascular disease] and CRC in adults 50 to 59 years of age who have a 10% or greater 10-year CVD risk, are not at increased risk for bleeding, have a life expectancy of at least 10 years, and are willing to take low-dose aspirin daily for at least 10 years”.[66]

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.[67][68] 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.[67][69]

Along with rheumatic fever, Kawasaki disease remains one of the few indications for aspirin use in children[70] in spite of a lack of high quality evidence for its effectiveness.[71]

Low-dose aspirin supplementation has moderate benefits when used for prevention of pre-eclampsia.[72][73] This benefit is greater when started in early pregnancy.[74] There is no evidence that aspirin prevents dementia.[75]

Resistance

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,[76] and a different, aggregate study of 2,930 people found 28% were resistant.[77] A study in 100 Italian people, though, found, of the apparent 31% aspirin-resistant subjects, only 5% were truly resistant, and the others were noncompliant.[78] Another study of 400 healthy volunteers found no subjects who were truly resistant, but some had "pseudoresistance, reflecting delayed and reduced drug absorption".[79]

Dosage

Coated 325 mg (5-grain) aspirin tablets
The 5-grain aspirin. The usage guidance label on a bottle of aspirin indicates that the dosage is "325 mg (5 gr)".

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 (1​14-grain) tablets are commonly called "baby aspirin" or "baby-strength", because they were originally—but no longer—intended to be administered to infants and children.[80] No medical significance occurs due to the slight difference in dosage between the 75 mg and the 81 mg tablets. The dose required for benefit appears to depend on a person's weight.[81] For those less than 70 kg low dose is effective for preventing cardiovascular disease while in those who weight more than 70 kg higher doses are required.[81]

In general, for adults, doses are taken four times a day for fever or arthritis,[82] with doses near the maximal daily dose used historically for the treatment of rheumatic fever.[83] For the prevention of myocardial infarction (MI) in someone with documented or suspected coronary artery disease, much lower doses are taken once daily.[82]

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 hemorrhage.[84] 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.[84] 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 people requiring aspirin for long-term prevention.[84]

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.[85]

Other Languages
Afrikaans: Aspirien
Alemannisch: Acetylsalicylsäure
العربية: أسبرين
asturianu: Aspirina
azərbaycanca: Asetilsalisilli turşu
Bân-lâm-gú: Aspirin
bosanski: Aspirin
Cymraeg: Aspirin
ދިވެހިބަސް: އެސްޕިރިން
eesti: Aspiriin
Ελληνικά: Ασπιρίνη
Esperanto: Aspirino
Gaeilge: Aspairín
galego: Aspirina
한국어: 아스피린
հայերեն: Ասպիրին
हिन्दी: एस्पिरिन
Bahasa Indonesia: Aspirin
עברית: אספירין
Kreyòl ayisyen: Aspirin
kurdî: Aspîrîn
lietuvių: Aspirinas
македонски: Аспирин
മലയാളം: ആസ്പിരിൻ
مازِرونی: آسپرین
Bahasa Melayu: Aspirin
Nederlands: Acetylsalicylzuur
नेपाल भाषा: एस्पिरिन
norsk nynorsk: Acetylsalisylsyre
occitan: Aspirina
ଓଡ଼ିଆ: ଆସ୍ପିରିନ
oʻzbekcha/ўзбекча: Atsetilsalitsil kislota
română: Aspirină
Scots: Aspirin
shqip: Aspirina
Simple English: Aspirin
کوردی: ئەسپیرین
српски / srpski: Аспирин
srpskohrvatski / српскохрватски: Aspirin
Tagalog: Aspirin
తెలుగు: ఆస్పిరిన్
Tsetsêhestâhese: Vonomóhtâhestôtse
Türkçe: Aspirin
اردو: ایسپرین
ئۇيغۇرچە / Uyghurche: ئاسپىرىن
Tiếng Việt: Aspirin
walon: Aspirene
文言: 阿司匹靈
Winaray: Aspirin
吴语: 阿司匹林
ייִדיש: אספירין
粵語: 阿士匹靈
žemaitėška: Eksperins
中文: 阿司匹林