Aspirin
Prescription aspirin is used to relieve the symptoms of rheumatoid arthritis (arthritis caused by swelling of the lining of the joints), osteoarthritis (arthritis caused by breakdown of the lining of the joints), systemic lupus erythematosus (condition in which the immune system attacks the joints and organs and causes pain and swelling) and certain other rheumatologic conditions (conditions in which the immune system attacks parts of the body). Nonprescription aspirin is used to reduce fever and to relieve mild to moderate pain from headaches, menstrual periods, arthritis, toothaches, and muscle aches. Nonprescription aspirin is also used to prevent heart attacks in people who have had a heart attack in the past or who have angina (chest pain that occurs when the heart does not get enough oxygen). Nonprescription aspirin is also used to reduce the risk of death in people who are experiencing or who have recently experienced a heart attack. Nonprescription aspirin is also used to prevent ischemic strokes (strokes that occur when a blood clot blocks the flow of blood to the brain) or mini-strokes (strokes that occur when the flow of blood to the brain is blocked for a short time) in people who have had this type of stroke or mini-stroke in the past. Aspirin will not prevent hemorrhagic strokes (strokes caused by bleeding in the brain). Aspirin is in a group of medications called salicylates. It works by stopping the production of certain natural substances that cause fever, pain, swelling, and blood clots.
aspirin
Aspirin is also available in combination with other medications such as antacids, pain relievers, and cough and cold medications. This monograph only includes information about the use of aspirin alone. If you are taking a combination product, read the information on the package or prescription label or ask your doctor or pharmacist for more information.
Prescription aspirin comes as an extended-release (long-acting) tablet. Nonprescription aspirin comes as a regular tablet, a delayed-release (releases the medication in the intestine to prevent damage to the stomach) tablet, a chewable tablet, powder, and a gum to take by mouth. Prescription aspirin is usually taken two or more times a day. Nonprescription aspirin is usually taken once a day to lower the risk of a heart attack or stroke. Nonprescription aspirin is usually taken every 4 to 6 hours as needed to treat fever or pain. Follow the directions on the package or prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take aspirin exactly as directed. Do not take more or less of it or take it more often than directed by the package label or prescribed by your doctor.
Ask a doctor before you give aspirin to your child or teenager. Aspirin may cause Reye's syndrome (a serious condition in which fat builds up on the brain, liver, and other body organs) in children and teenagers, especially if they have a virus such as chicken pox or the flu.
Stop taking aspirin and call your doctor if your fever lasts longer than 3 days, if your pain lasts longer than 10 days, or if the part of your body that was painful becomes red or swollen. You may have a condition that must be treated by a doctor.
If your doctor has told you to take aspirin on a regular basis and you miss a dose, take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.
Aspirin, also known as acetylsalicylic acid (ASA), is a nonsteroidal anti-inflammatory drug (NSAID) used to reduce pain, fever, and/or inflammation, and as an antithrombotic.[8] Specific inflammatory conditions which aspirin is used to treat include Kawasaki disease, pericarditis, and rheumatic fever.[8]
Like flour mills, factories producing aspirin tablets must control the amount of the powder that becomes airborne inside the building, because 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 mg/m3 (time-weighted average).[20] In 1989, the Occupational Safety and Health Administration (OSHA) set a legal permissible exposure limit for aspirin of 5 mg/m3, but this was vacated by the AFL-CIO v. OSHA decision in 1993.[21]
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.[23]
Polymorphism, or the ability of a substance to form more than one crystal structure, is important in the development of pharmaceutical ingredients. Many drugs receive regulatory approval for only a single crystal form or polymorph. For a long time, only one crystal structure for aspirin was known. That aspirin might have a second crystalline form was suspected since the 1960s. The elusive second polymorph was first discovered by Vishweshwar and coworkers in 2005,[28] and fine structural details were given by Bond et al.[29] A new crystal type was found during experiments after co-crystallization of aspirin and levetiracetam from hot acetonitrile. The form II is only stable at 100 K and reverts to form I at ambient temperature. In the (unambiguous) form I, two salicylic molecules form centrosymmetric dimers through the acetyl groups with the (acidic) methyl proton to carbonyl hydrogen bonds, and in the newly claimed form II, each salicylic molecule forms the same hydrogen bonds with two neighboring molecules instead of one. With respect to the hydrogen bonds formed by the carboxylic acid groups, both polymorphs form identical dimer structures.[28]
In 1971, British pharmacologist John Robert Vane, then employed by the Royal College of Surgeons in London, showed aspirin suppressed the production of prostaglandins and thromboxanes.[30][31] For this discovery he was awarded the 1982 Nobel Prize in Physiology or Medicine, jointly with Sune Bergström and Bengt Ingemar Samuelsson.[32]
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 PTGS enzyme (Suicide inhibition). This makes aspirin different from other NSAIDs (such as diclofenac and ibuprofen), which are reversible inhibitors.
Prostaglandins, local hormones produced in the body, have diverse effects, including the transmission of pain information to the brain, modulation of the hypothalamic thermostat, and inflammation. Thromboxanes are responsible for the aggregation of platelets that form 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.[35]
At least two different types of cyclooxygenases, 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 prostanoids, most of which are proinflammatory. Aspirin-modified PTGS2 (prostaglandin-endoperoxide synthase 2) produces lipoxins, most of which are anti-inflammatory.[36][verification needed] Newer NSAID drugs, COX-2 inhibitors (coxibs), have been developed to inhibit only PTGS2, with the intent to reduce the incidence of gastrointestinal side effects.[12]
Several COX-2 inhibitors, such as rofecoxib (Vioxx), have been withdrawn from the market, after evidence emerged that PTGS2 inhibitors increase the risk of heart attack and stroke.[37][38] Endothelial cells lining the microvasculature in the body are proposed to express PTGS2, and, by selectively inhibiting PTGS2, prostaglandin production (specifically, PGI2; prostacyclin) is downregulated with respect to thromboxane levels, as PTGS1 in platelets is unaffected. Thus, the protective anticoagulative effect of PGI2 is removed, increasing the risk of thrombus and associated heart attacks and other circulatory problems. Since platelets have no DNA, they are unable to synthesize new PTGS once aspirin has irreversibly inhibited the enzyme, an important difference as compared with reversible inhibitors.
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 lipoxins, aspirin-triggered resolvins, and aspirin-triggered maresins. 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.[39][40][41]
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.[42] Aspirin buffers and transports the protons. When high doses are given, it may actually cause fever, owing to the heat released from the electron transport chain, as opposed to the antipyretic action of aspirin seen with lower doses. In addition, aspirin induces the formation of NO-radicals in the body, which have been shown in mice to have an independent mechanism of reducing inflammation. This reduced leukocyte adhesion is an important step in the immune response to infection; however, evidence is insufficient to show aspirin helps to fight infection.[43] More recent data also suggest salicylic acid and its derivatives modulate signalling through NF-κB.[44] NF-κB, a transcription factor complex, plays a central role in many biological processes, including inflammation.[45][46][47] 041b061a72