| Drug ID: | D018 |
| Drug Name: | Aspirin |
| Synonyms: |
2-Acetoxybenzenecarboxylic acid; 2-Acetoxybenzoic acid; Acetylsalicylate; ASA; Aspirin; o-acetoxybenzoic acid; O-acetylsalicylic acid; o-carboxyphenyl acetate; Salicylic acid acetate
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| Type: | Chemical drug |
| DrugBank ID: |
DB00945
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| DrugBank Description: |
Also known as _Aspirin_, acetylsalicylic acid (ASA) is a commonly used drug for the treatment of pain and fever due to various causes. Acetylsalicylic acid has both anti-inflammatory and antipyretic effects. This drug also inhibits platelet aggregation and is used in the prevention of blood clots stroke, and myocardial infarction (MI) .
Interestingly, the results of various studies have demonstrated that long-term use of acetylsalicylic acid may decrease the risk of various cancers, including colorectal, esophageal, breast, lung, prostate, liver and skin cancer . Aspirin is classified as a _non-selective cyclooxygenase (COX) inhibitor_ and is available in many doses and forms, including chewable tablets, suppositories, extended release formulations, and others .
Acetylsalicylic acid is a very common cause of accidental poisoning in young children. It should be kept out of reach from young children, toddlers, and infants .
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| PubChem ID: |
2244
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| CasNo: |
50-78-2
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| Repositioning for NAFLD: |
Yes
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| SMILES: |
C(=O)(O)c1c(OC(=O)C)cccc1
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| Structure: |
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| InChiKey: |
BSYNRYMUTXBXSQ-UHFFFAOYSA-N
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| Molecular Weight: |
180.159
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| DrugBank Targets: |
Prostaglandin G/H synthase 1 inhibitor; Prostaglandin G/H synthase 2 inhibitor; Aldo-keto reductase family 1 member C1 inhibitor; 5'-AMP-activated protein kinase activator; Endothelin-1 receptor inhibitor; Cellular tumor antigen p53 inducer; 78 kDa glucos
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| DrugBank MoA: |
Acetylsalicylic acid (ASA) blocks prostaglandin synthesis. It is non-selective for COX-1 and COX-2 enzymes . Inhibition of COX-1 results in the inhibition of platelet aggregation for about 7-10 days (average platelet lifespan). The acetyl group of acetylsalicylic acid binds with a serine residue of the cyclooxygenase-1 (COX-1) enzyme, leading to irreversible inhibition. This prevents the production of pain-causing prostaglandins. This process also stops the conversion of arachidonic acid to thromboxane A2 (TXA2), which is a potent inducer of platelet aggregation . Platelet aggregation can result in clots and harmful venous and arterial thromboembolism, leading to conditions such as pulmonary embolism and stroke.
It is important to note that there is 60% homology between the protein structures of COX-1 and COX-2. ASA binds to serine 516 residue on the active site of COX-2 in the same fashion as its binding to the serine 530 residue located on the active site of COX-1. The active site of COX-2 is, however, slightly larger than the active site of COX-1, so that arachidonic acid (which later becomes prostaglandins) manages to bypass the aspirin molecule inactivating COX-2 . ASA, therefore, exerts more action on the COX-1 receptor rather than on the COX-2 receptor . A higher dose of acetylsalicylic acid is required for COX-2 inhibition .
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| DrugBank Pharmacology: |
**Effects on pain and fever**
Acetylsalicylic acid disrupts the production of prostaglandins throughout the body by targeting cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) . Prostaglandins are potent, irritating substances that have been shown to cause headaches and pain upon injection into humans. Prostaglandins increase the sensitivity of pain receptors and substances such as histamine and bradykinin. Through the disruption of the production and prevention of release of prostaglandins in inflammation, this drug may stop their action at pain receptors, preventing symptoms of pain. Acetylsalicylic acid is considered an antipyretic agent because of its ability to interfere with the production of brain prostaglandin E1. Prostaglandin E1 is known to be an extremely powerful fever-inducing agent .
**Effects on platelet aggregation**
The inhibition of platelet aggregation by ASA occurs because of its interference with thromboxane A2 in platelets, caused by COX-1 inhibition. Thromboxane A2 is an important lipid responsible for platelet aggregation, which can lead to clot formation and future risk of heart attack or stroke .
**A note on cancer prevention**
ASA has been studied in recent years to determine its effect on the prevention of various malignancies . In general, acetylsalicylic acid is involved in the interference of various cancer signaling pathways, sometimes inducing or upregulating tumor suppressor genes . Results of various studies suggest that there are beneficial effects of long-term ASA use in the prevention of several types of cancer, including stomach, colorectal, pancreatic, and liver cancers . Research is ongoing.
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| DrugBank Indication: |
**Pain, fever, and inflammation**
Acetylsalicylic acid (ASA), in the regular tablet form (immediate-release), is indicated to relieve pain, fever, and inflammation associated with many conditions, including the flu, the common cold, neck and back pain, dysmenorrhea, headache, tooth pain, sprains, fractures, myositis, neuralgia, synovitis, arthritis, bursitis, burns, and various injuries. It is also used for symptomatic pain relief after surgical and dental procedures .
The _extra strength_ formulation of acetylsalicylic acid is also indicated for the management migraine pain with photophobia (sensitivity to light) and phonophobia (sensitivity to sound).
**Other indications**
ASA is also indicated for various other purposes, due to its ability to inhibit platelet aggregation. These include:
Reducing the risk of cardiovascular death in suspected cases of myocardial infarction (MI) .
Reducing the risk of a first non-fatal myocardial infarction in patients, and for reducing the risk of morbidity and mortality in cases of unstable angina and in those who have had a prior myocardial infarction .
For reducing the risk of transient ischemic attacks (TIA) and to prevent atherothrombotic cerebral infarction (in conjunction with other treatments) .
For the prevention of thromboembolism after hip replacement surgery .
For decreasing platelet to platelet adhesion following carotid endarterectomy, aiding in the prevention of transient ischemic attacks (TIA) .
Used for patients undergoing hemodialysis with a silicone rubber arteriovenous cannula inserted to prevent thrombosis at the insertion site .
**Important note regarding use of the extended-release formulation **
In the setting of acute myocardial infarction, or before percutaneous interventions, the extended-release form of acetylsalicylic acid should not be used. Use immediate-release formulations in scenarios requiring rapid onset of action . The extended-release form is taken to decrease the incidence of mortality and myocardial infarction (MI) for individuals diagnosed with chronic coronary artery disease (CAD), including patients with previous myocardial infarction (MI) or unstable angina or with chronic stable angina. Additionally, the extended-release form is used to decrease the risk of death and recurrent episodes of stroke in patients with a history of stroke or TIA .
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| Targets: |
AKR1C1 inhibitor; PCNA downregulator
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| Therapeutic Category: |
Enhance lipid metabolism
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| Clinical Trial Progress: |
Phase 1&2 on-going (NCT04031729)
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| Latest Progress: |
Under clinical trials
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