Drug/Small Molecule:

aspirin

Overview

Generic Names:	2-Acetoxybenzenecarboxylic acid; 2-Acetoxybenzoic acid; 2-Carboxyphenyl acetate; A.S.A.; ASA; Acetilsalicilico; Acetilum acidulatum; Acetosalic acid; Acetoxybenzoic acid; Acetylsalicylate; Acetylsalicylic acid; Acetylsalicylsaure (GERMAN); Acetysalicylic acid; Acide acetylsalicylique (FRENCH); Acido O-acetil-benzoico; Acido acetilsalicilico; Acidum acetylsalicylicum; Kyselina 2-acetoxybenzoova; Kyselina acetylsalicylova; O-Acetylsalicylic acid; O-accetylsalicylic acid; Salicylic acid acetate; Salicylic acid, acetate; o-Acetoxybenzoic acid; o-Carboxyphenyl acetate
IUPAC Name:	2-acetyloxybenzoic acid
Trade Names:	8-hour Bayer; A.S.A. Empirin; Acenterine; Acesal; Acetal; Aceticyl; Acetisal; Acetol; Acetonyl; Acetophen; Acetosal; Acetosalin; Acetylin; Acetylsal; Acimetten; Acisal; Acylpyrin; Adiro; Asagran; Asatard; Ascoden-30; Aspalon; Aspec; Aspergum; Aspirdrops; Aspirine; Aspro; Asteric; Bayer Extra Strength Aspirin For Migraine Pain; Benaspir; Bi-prin; Bialpirina; Bialpirinia; Bufferin; Caprin; Cemirit; Claradin; Clariprin; Colfarit; Contrheuma retard; Coricidin; Crystar; Decaten; Delgesic; Dolean pH 8; Duramax; ECM; Easprin; Ecolen; Ecotrin; Empirin; Endydol; Entericin; Enterophen; Enterosarein; Enterosarine; Entrophen; Extren; Globentyl; Globoid; Helicon; Idragin; Levius; Measurin; Micristin; Neuronika; Novid; Nu-seals; Nu-seals aspirin; Persistin; Pharmacin; Pirseal; Polopiryna; Premaspin; Rheumintabletten; Rhodine; Rhonal; Salacetin; Salcetogen; Saletin; Solfrin; Solprin; Solprin acid; Solpyron; Spira-Dine; St. Joseph; St. Joseph Aspirin for Adults; Supac; Tasprin; Temperal; Triaminicin; Triple-sal; Vanquish; Xaxa; Yasta
Brand Mixtures:	Aspirin Plus Stomach Guard (Acetylsalicylic Acid + Calcium Carbonate + Magnesium Carbonate + Magnesium Oxide); Aspirin Plus Stomach Guard Ext.Stgth.Caplet (Acetylsalicylic Acid + Calcium Carbonate + Magnesium Carbonate + Magnesium Oxide); Aspirin Plus Stomach Guard Extra Strength (Acetylsalicylic Acid + Calcium Carbonate + Magnesium Carbonate + Magnesium Oxide); Aspirin Plus Stomach Guard Tab (Acetylsalicylic Acid + Calcium Carbonate + Magnesium Carbonate + Magnesium Oxide); Aspirin with Stomach Guard (Acetylsalicylic Acid + Calcium Carbonate + Magnesium Carbonate + Magnesium Oxide); Aspirin with Stomach Guard Extra Strength - Tab (Acetylsalicylic Acid + Calcium Carbonate + Magnesium Carbonate + Magnesium Oxide); Extra Strength Aspirin Backache (Acetylsalicylic Acid + Methocarbamol)
PharmGKB Accession Id:	PA448497

Description

The prototypical analgesic used in the treatment of mild to moderate pain. It has anti-inflammatory and antipyretic properties and acts as an inhibitor of cyclooxygenase which results in the inhibition of the biosynthesis of prostaglandins. Aspirin also inhibits platelet aggregation and is used in the prevention of arterial and venous thrombosis. (From Martindale, The Extra Pharmacopoeia, 30th ed, p5)

Indication

For use in the temporary relief of various forms of pain, inflammation associated with various conditions (including rheumatoid arthritis, juvenile rheumatoid arthritis, systemic lupus erythematosus, osteoarthritis, and ankylosing spondylitis), and is also used to reduce the risk of death and/or nonfatal myocardial infarction in patients with a previous infarction or unstable angina pectoris.

ATC Therapeutic Categories

• A01AD:Other agents for local oral treatment
• B01AC:Platelet aggregation inhibitors excl. heparin
• N02BA:Salicylic acid and derivatives

Pharmacology and Interactions

Mechanism Of Action

The analgesic, antipyretic, and anti-inflammatory effects of aspirin are due to actions by both the acetyl and the salicylate portions of the intact molecule as well as by the active salicylate metabolite. Aspirin directly and irreversibly inhibits the activity of both types of cyclo-oxygenase (COX-1 and COX-2) to decrease the formation of precursors of prostaglandins and thromboxanes from arachidonic acid. This makes aspirin different from other NSAIDS (such as diclofenac and ibuprofen) which are reversible inhibitors. Salicylate may competitively inhibit prostaglandin formation. Aspirin's antirheumatic (nonsteroidal anti-inflammatory) actions are a result of its analgesic and anti-inflammatory mechanisms; the therapeutic effects are not due to pituitary-adrenal stimulation. The platelet aggregation–inhibiting effect of aspirin specifically involves the compound's ability to act as an acetyl donor to the platelet membrane; the nonacetylated salicylates have no clinically significant effect on platelet aggregation. Aspirin affects platelet function by inhibiting the enzyme prostaglandin cyclooxygenase in platelets, thereby preventing the formation of the aggregating agent thromboxane A2. This action is irreversible; the effects persist for the life of the platelets exposed. Aspirin may also inhibit formation of the platelet aggregation inhibitor prostacyclin (prostaglandin I2) in blood vessels; however, this action is reversible.

Pharmacology

Aspirin (acetylsalicylic acid) is an analgesic, antipyretic, antirheumatic, and anti-inflammatory agent. Aspirin's mode of action as an antiinflammatory and antirheumatic agent may be due to inhibition of synthesis and release of prostaglandins. Aspirin appears to produce analgesia by virtue of both a peripheral and CNS effect. Peripherally, Aspirin acts by inhibiting the synthesis and release of prostaglandins. Acting centrally, it would appear to produce analgesia at a hypothalamic site in the brain, although the mode of action is not known. Aspirin also acts on the hypothalamus to produce antipyresis; heat dissipation is increased as a result of vasodilation and increased peripheral blood flow. Aspirin's antipyretic activity may also be related to inhibition of synthesis and release of prostaglandins.

Food Interactions

Avoid alcohol, alcohol appears to cause a 50 to 100% increases in ASA serum levels. Avoid drastic changes in dietary habit. Consult your doctor before taking large amounts of Vitamin K (Green leafy vegetables). Take with a full glass of water. Take with food to reduce irritation.

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Aspirin is rapidly hydrolyzed primarily in the liver to salicylic acid, which is conjugated with glycine (forming salicyluric acid) and glucuronic acid and excreted largely in the urine.

Protein Binding

High (99.5%) to albumin. Decreases as plasma salicylate concentration increases, with reduced plasma albumin concentration or renal dysfunction, and during pregnancy.

Absorption

Absorption is generally rapid and complete following oral administration but may vary according to specific salicylate used, dosage form, and other factors such as tablet dissolution rate and gastric or intraluminal pH.

Half Life

The plasma half-life is approximately 15 minutes; that for salicylate lengthens as the dose increases: doses of 300 to 650 mg have a half-life of 3.1 to 3.2 hours; with doses of 1 gram, the half-life is increased to 5 hours and with 2 grams it is increased to about 9 hours.

Toxicity

Oral, mouse: LD₅₀ = 250 mg/kg; Oral, rabbit: LD₅₀ = 1010 mg/kg; Oral, rat: LD₅₀ = 200 mg/kg. Effects of overdose include: tinnitus, abdominal pain, hypokalemia, hypoglycemia, pyrexia, hyperventilation, dysrhythmia, hypotension, hallucination, renal failure, confusion, seizure, coma, and death.

Chemical Properties

Chemical Formula:

C₉H₈O₄

SMILES Code:

CC(=O)Oc1ccccc1C(=O)O

(Format: OpenEye Isomeric)

Molecular Weight ( average / monoisotopic )

180.1574 / 180.0423

Curated Annotations ()

1. rs2768759 at chr1:155119087 in NTRK1
   This variant is associated with enhanced agonist-induced platelet aggragation and response to aspirin in both whites and african americans. The C allele was associated with increased aggregation of native platelets to collagen, epinephrine. The C allele was also associated with reduced platelet responsiveness to aspirin. (N=1486)

   Related Drugs:

   aspirin

   Evidence:

   PMID:18511696
   

2. rs2046934 at chr3:152540332 in MED12L, P2RY12
   This is one of four SNPs that comprise H1/H2 haplotypes. The four SNPs (C139T, T744C, ins801A, G52T(=G50T) are in perfect LD, and T744C is frequently used as the tagging SNP. H1 is 139C/744T/no ins at 801A/52G. H2(minor haplotype) is 139T/744C/ins801A//52T. H2 haplotype has been found to be associated with enhanced platelet reactivity, peripheral artery disease, coronary artery disease(particularly in non-smokers)and with poor response to clopidogrel. In other studies, no association was found between haplotype and response to clopidogrel or aspirin or with cardiovascular events.

   Variant Name:

   P2RY12:T744C,P2RY12:i-T744C

   Related Drugs:

   aspirin, clopidogrel

   Related Diseases:

   Coronary Artery Disease, Peripheral Vascular Diseases

   Evidence:

   PMID:12912815
   PMID:14662702
   PMID:15795539
   PMID:16181985
   PMID:16405973
   PMID:16581111
   PMID:16769602
   PMID:16961627
   PMID:17337040
   PMID:17803810
   

3. rs730012 at chr5:179153244 in LTC4S
   A two-family study indicates that aspirin-induced urticaria aggregates in families in which the C allele of this SNP is present.

   Variant Name:

   LTC4S:-444C

   Related Drugs:

   aspirin

   Related Diseases:

   Urticaria

   Evidence:

   PMID:16433794
   

4. rs730012 at chr5:179153244 in LTC4S
   Risk or phenotype-associated allele: C. Phenotype: A-444C was associated with aspirin-induced urticaria (AIU). The C allele was more frequent in patients with the cutaneous pattern of AIU and in patients with low skin reactivity to histamine. Study size: 110 patients with AIU and 165 nonallergic controls .

   Variant Name:

   LTC4S: A-444C

   Related Drugs:

   aspirin

   Related Diseases:

   Urticaria

   Evidence:

   PMID:19862937
   

5. rs5918 at chr17:42715729 in ITGB3
   Risk or phenotype-associated allele: C. Phenotype: In a study of clotting times of microvascular injury, the P1A2 allele (C variant) was associated with shorter bleeding time and less response to aspirin. Study size: 24. Study population/ethnicity: Healthy males 21-24 years. Significance metric(s): p = 0.003. Type of association: PD.

   Variant Name:

   ITGB3:1565T>C, ITGB3:Leu33Pro, P1A2, PIA1/PIA2, Leu33Pro polymorphism of ß3 integrins, GP3A PIA2, GP IIIa HPA-1, HPA-1b

   Related Drugs:

   aspirin

   Evidence:

   PMID:11723016
   

Curated Information

The following genes are in curated knowledge about this drug.

Non-Curated Information

A list of non-curated publications that mention this drug along with other genes is available.

Drug Targets

• PTGS2
• PTGS1

PharmGKB Curated Pathways

• Celecoxib Pathway
• Platelet Aggregation Pathway (PD)

BioCarta Pathways†

• aspirin blocks signaling pathway involved in platelet activation - (BioCarta via Pathway Interaction Database)

Curated Information

The following drugs are in curated knowledge about this drug.

	Drug	Relationship	Evidence
	Proton pump inhibitors	CO	Publications
	warfarin	CO PD	Publications

Non-Curated Information

A list of non-curated publications that mention this drug along with other drugs is available.

Drug Interactions

Curated Information

The following diseases are in curated knowledge about this drug.

Non-Curated Information

A list of non-curated publications that mention this drug along with other diseases is available.

Curated Phenotype Datasets

These datasets are sorted alphabetically by title.

1. IWPC Warfarin Data Set (NEJM 2009)

   • 
   • 
   • 
   • 
   • PD
   • PK
   • GN

   Submitted by Warfarin Consortium involving CYP2C9, VKORC1, amiodarone, aspirin, simvastatin, warfarin, and Atrial Fibrillation
2. Use of Pharmacogenetic and Clinical Factors to Predict the Therapeutic Dose of Warfarin

   • 
   • 
   • 
   • 
   • PD
   • PK
   • GN

   Submitted by Brian Gage, MD involving CYP2C9, VKORC1, amiodarone, aspirin, simvastatin, warfarin, , Atrial Fibrillation, post-orthopedic, Pulmonary Embolism, Stroke and Venous Thrombosis

Additional Datasets

These datasets are minimally curated and are sorted alphabetically by title.

1. IWPC Pharmacogenetic Dosing Algorithm
2. Physicochemical determinants of human renal clearance

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Non-Curated Publications

A list of non-curated publications that mention this drug is available.