Acylpyrin - General Information
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. Acylpyrin also inhibits platelet aggregation and is used in the prevention of arterial and venous thrombosis. (From Martindale, The Extra Pharmacopoeia, 30th ed, p5)
Pharmacology of Acylpyrin
Acylpyrin (acetylsalicylic acid) is an analgesic, antipyretic, antirheumatic, and anti-inflammatory agent. Acylpyrin's mode of action as an antiinflammatory and antirheumatic agent may be due to inhibition of synthesis and release of prostaglandins. Acylpyrin appears to produce analgesia by virtue of both a peripheral and CNS effect. Peripherally, Acylpyrin 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. Acylpyrin also acts on the hypothalamus to produce antipyresis; heat dissipation is increased as a result of vasodilation and increased peripheral blood flow. Acylpyrin's antipyretic activity may also be related to inhibition of synthesis and release of prostaglandins.
Acylpyrin for patients
New Prescribed Uses of Aspirin: Questions and Answers
October 20, 1998 - U.S. Food and Drug Administration
Q. What professional uses of aspirin are now indicated?
2) HEART ATTACKS:
- reduces the risk of death in patients with suspected acute heart attacks (myocardial infarctions)
- prevents recurrent heart attacks and
- reduces the risk of heart attacks or sudden death in patients with unstable and chronic stable angina pectoris (chest pain).
3) OTHER CORONARY CONDITIONS: Aspirin can be used to treat patients who have had certain revascularization procedures such as angioplasty, and coronary bypass operations -- if they have a vascular condition for which aspirin is already indicated.
4) RHEUMATOLOGIC DISEASES -- Aspirin is indicated for relief of the signs and symptoms of rheumatoid arthritis, juvenile rheumatoid arthritis, osteoarthritis, spondylarthropathies, and arthritis and pleurisy associated with systemic lupus erythematosus.
Q. What does this mean for doctors and medical practice?
A. Doctors and health care professionals will be provided with full prescribing information about the use of aspirin in both men and women who have had a heart attack, stroke, certain other cardiovascular conditions and rheumatologic diseases. For stroke and cardiovascular conditions, lower doses are recommended than those previously prescribed by physicians in practice. Information on the use of aspirin for rheumatologic diseases has also been expanded to include specific dosing information as well as information about side effects and toxicity. Thus, doctors will have full prescribing information on aspirin and the assurance that aspirin is a safe and effective treatment for heart attacks, strokes, certain other vascular conditions and rheumatologic diseases.
Q. What is the basis for the new prescribing information?
A. The new information on the uses of aspirin is based on scientific studies that support treatment with aspirin for heart attacks, strokes, and some related conditions. Convincing data support these uses in lower doses than previously believed to be effective in treating heart attacks and strokes in both men and women.
Q. What does this mean for patients?
A. Physicians will be better able to prescribe the proper doses for these uses for male and female patients with these medical conditions. Dose-related adverse events for patients with stroke and cardiovascular conditions should be minimized because lower dosages are recommended. The full prescribing information now provided for physicians who treat rheumatologic diseases will enhance the safe and effective prescribing of aspirin to these patients as well.
Q. Is FDA concerned that some patients may self-treat?
A. FDA emphasizes that consumers should not self-medicate for these serious conditions because it is very important to make sure that aspirin is their best treatment. In these conditions, the risk and benefit of each available treatment for each patient must be carefully weighed. Patients with these conditions should be under the care and supervision of a doctor.
Q. If a consumer is interested in using aspirin to prevent or treat symptoms of heart problems, what should he or she do?
A. Consumers should always first ask their doctor. In fact, aspirin products are labeled this way: "Important: See your doctor before taking this product for other new uses of aspirin because serious side effects could occur with self treatment."
Q. Do the data on treatment or prevention of cardiovascular effects pertain only to aspirin?
A. Yes. Although acetaminophen, ibuprofen, naproxyn sodium and ketoprofen are good drugs for pain and fever, as is aspirin, only aspirin has demonstrated a beneficial effect for heart attack and stroke.
Q. What should consumers be made aware of?
A. Consumers should be informed that these new professional uses of aspirin may be lifesaving when used upon the recommendation and under the supervision of a doctor. However, they must also be informed that even familiar and readily available products like aspirin may have important risks when used in new ways. For example, because aspirin can cause bleeding; in rare cases bleeding in the brain may occur in people who are using aspirin to prevent stroke. Therefore these new uses should be recommended and monitored by a physician.
Q. What should consumers who are taking low dose aspirin for disease maintenance or prevention know about alcohol use?
A. Patients who consume 3 or more alcoholic drinks every day should be counseled about the bleeding risks involved with chronic, heavy alcohol use while taking aspirin.
Q. Can consumers safely use aspirin to treat suspected acute heart attacks?
A. If consumers suspect they are having a heart attack, their most important action must be to seek emergency medical care immediately. The advise and supervision of a doctor should direct this use of aspirin and patients are encouraged to speak with their doctor about this use.
Q. What do we know about how aspirin works for heart conditions and stroke?
A. The mechanism by which aspirin works in the treatment of heart attack and stroke is not completely understood. However, as an antiplatelet drug, we do know that aspirin help reduce platelet clumping which helps cause blockage in blood vessels.
Q. Who should NOT take aspirin?
A. Generally, people who have:
- allergy to aspirin or other salicylates
- uncontrolled high blood pressure
- severe liver or kidney disease
- bleeding disorders
Always check first with your doctor to determine whether the benefit of these professional uses of aspirin is greater than the risks to you.
Q. What other side effects are associated with aspirin?
A. There is a wide range of adverse reactions that may result from aspirin use including effects on the body as a whole, or on specific body systems and functions.
High doses can cause hearing loss or tinnitus -- ringing in the ears. (Note that this usually only occurs with large doses as prescribed in rheumatologic diseases and is rare in treatment with low doses used for cardiovascular purposes.)
Q. What is key message for Consumers?
A. The results of studies of people with a history of coronary artery disease and those in the immediate phases of a heart attack have proven to be of tremendous importance in the prevention and treatment of cardiovascular and cerebrovascular diseases.
Studies showed that aspirin substantially reduces the risk of death and/ or non-fatal heart attacks in patients with a previous MI or unstable angina pectoris which often occur before a heart attack. Patients with these conditions should be under the care and supervision of a doctor.
Aspirin has potential risks as well as benefits, like any drug. Patients should be careful to ask their doctor or health care professional before deciding whether aspirin is right for them and how much aspirin they should take.
Q. What were the major studies used to verify the effectiveness of aspirin for these indications?
A. Numerous studies both in the United States and abroad were evaluated to establish the safety and efficacy of aspirin for the cardiovascular and cerebrovascular indications and dosing information.
Major studies included:
ISIS - 2 (Second International Study of Infarct Survival) (Ref 7)
SALT (Swedish Aspirin Low-Dose Trial (Ref 22)
ESPS-2 (European Stroke Prevention Study (Ref 23)
UK-TIA (United Kingdom Transient Ischaemic Attack) Aspirin Trial (Ref 11)
SAPAT (Stable Angina Pectoris Aspirin Trial) (Ref. 27)
Canadian Cooperative Study Group (Ref. 8)
W.S. Fields et al., Controlled Trial of Aspirin in Cerebral Ischemia (Ref 10)
* Note the reference numbers refer to the citations in the Final Rule. (Food and Drug Administration. Internal analgesic, antipyretic, and antirheumatic drug products for over the counter human use; final rule for professional labeling of aspirin, buffered aspirin, and aspirin in combination with antacid drug products. Federal Register. October 23, 1998; 63:56802-56819.)
Uricosuric Agents: Aspirin may decrease the effects of probenecid, sulfinpyrazone, and phenylbutazone.
Alcohol: Has a synergistic effect with aspirin in causing gastrointestinal bleeding.
Corticosteroids: Concomitant administration with aspirin may increase the risk of gastrointestinal ulceration and may reduce serum salicylate levels.
Pyrazolone Derivatives (phenylbutazone, oxyphenbutazone, and possibly dipyrone): Concomitant administration with aspirin may increase the risk of gastrointestinal ulceration.
Nonsteroidal Antiinflammatory Agents: Aspirin is contraindicated in patients who are hypersensitive to nonsteroidal anti-inflammatory agents.
Urinary Alkalinizers: Decrease aspirin effectiveness by increasing the rate of salicylate renal excretion.
Phenobarbital: Decreases aspirin effectiveness by enzyme induction.
Phenytoin: Serum phenytoin levels may be increased by aspirin.
Propranolol: May decrease aspirin's anti-inflammatory action by competing for the same receptors. Antacids: Enteric Coated Aspirin should not be given concurrently with antacids, since an increase in the pH of the stomach may effect the enteric coating of the tablets.
Aspirin should not be used in patients who have previously exhibited hypersensitivity to aspirin and/or nonsteroidal antiinflammatory agents. Aspirin should not be given to patients with a recent history of gastrointestinal bleeding or in patients with bleeding disorders (e.g., hemophilia).
Additional information about Acylpyrin
Acylpyrin 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.
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. Acylpyrin 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. Acylpyrin'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. Acylpyrin 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. Acylpyrin may also inhibit formation of the platelet aggregation inhibitor prostacyclin (prostaglandin I2) in blood vessels; however, this action is reversible.
Drug Interactions: Acetazolamide The salicylate at high dose increases the effect of the carbonic anyhydrase
Acetohexamide The salicylate increases the effect of sulfonylurea
Methotrexate The salicylate increases the effect and toxicity of methotrexate
Anisindione The salicylate increases effect of anticoagulant
Betamethasone The corticosteroid decreases the effect of salicylates
Chlorpropamide The salicylate increases the effect of sulfonylurea
Dexamethasone The corticosteroid decreases the effect of salicylates
Dichlorphenamide The salicylate at high dose increases the effect of the carbonic anyhydrase inhibitors
Dicumarol The salicylate increases effect of anticoagulant
Valproic Acid The salicylate increases the effect of valproic acid
Fludrocortisone The corticosteroid decreases the effect of salicylates
Gliclazide The salicylate increases the effect of sulfonylurea
Glipizide The salicylate increases the effect of sulfonylurea
Glisoxepide The salicylate increases the effect of sulfonylurea
Glibenclamide The salicylate increases the effect of sulfonylurea
Tolazamide The salicylate increases the effect of sulfonylurea
Tolbutamide The salicylate increases the effect of sulfonylurea
Griseofulvin Anticipate decrease of ASA efficiency in presence of griseofulvin
Heparin Association of ASA/heparin increases risk of bleeding
Hydrocortisone The corticosteroid decreases the effect of salicylates
Prednisolone The corticosteroid decreases the effect of salicylates
Prednisone The corticosteroid decreases the effect of salicylates
Triamcinolone The corticosteroid decreases the effect of salicylates
Warfarin The salicylate increases the effect of anticoagulant
Acenocoumarol The salicylate increases the effect of anticoagulant
Methylprednisolone The corticosteroid decreases the effect of salicylates
Ibuprofen Ibuprofen reduces ASA cardioprotective effects
Insulin-aspart The salicylate increases the effect of insulin
Insulin-detemir The salicylate increases the effect of insulin
Insulin-glargine The salicylate increases the effect of insulin
Insulin-glulisine The salicylate increases the effect of insulin
Insulin-lispro The salicylate increases the effect of insulin
Ketorolac ASA increases toxicity of ketorolac
Methazolamide The salicylate at high dose increases the effect of the carbonic anhydrase inhibitors
Probenecid The salicylate decreases the uricosuric effect of probenecid
Sulfinpyrazone The salicylate antagonizes the uricosuric effect of sulfinpyrazone
Ticlopidine Increased effect of ticlopidine
Cortisone acetate The corticosteroid decreases the effect of salicylates
Ginkgo biloba Association of ASA/ginkgo increases risk of bleeding
Glycodiazine The salicylate increases the effect of sulfonylurea
Insulin The salicylate increases the effect of insulin
Paramethasone The corticosteroid decreases the effect of salicylates
Food Interactions: Avoid drastic changes in dietary habit.
Consult your doctor before taking large amounts of Vitamin K (Green leafy vegetables).
Avoid alcohol, alcohol appears to cause a 50 to 100% increases in ASA serum levels.
Take with food to reduce irritation.
Take with a full glass of water.
Generic Name: Aspirin
Synonyms: 2-Acetoxybenzenecarboxylic acid; 2-Acetoxybenzoic acid; 2-Carboxyphenyl acetate; A.S.A.; Acetosalic acid; Acetoxybenzoic acid; Acetylsalicylsaure (GERMAN); Acetylsalicylic acid; Acetylsalicylate; Acetysalicylic acid; Acide acetylsalicylique (FRENCH); Acido acetilsalicilico; Acido O-acetil-benzoico; Acidum acetylsalicylicum; Acetilum acidulatum; Acetilsalicilico; ASA; O-accetylsalicylic acid; o-Acetoxybenzoic acid; O-Acetylsalicylic acid; o-Carboxyphenyl acetate; Salicylic acid acetate; Salicylic acid, acetate; Kyselina 2-acetoxybenzoova; Kyselina acetylsalicylova
Drug Category: Anti-Inflammatory Agents, Non-Steroidal; Cyclooxygenase Inhibitors; Fibrinolytic Agents; Anticoagulants; Salicylates
Drug Type: Small Molecule; Approved
Other Brand Names containing Aspirin: 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; 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;
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.
Toxicity (Overdose): 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.
Protein Binding: High (99.5%) to albumin. Decreases as plasma salicylate concentration increases, with reduced plasma albumin concentration or renal dysfunction, and during pregnancy.
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.
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.
Dosage Forms of Acylpyrin: Solution / drops Oral
Tablet, chewable Oral
Tablet, coated Oral
Tablet, delayed release Oral
Chemical IUPAC Name: 2-acetyloxybenzoic acid
Chemical Formula: C9H8O4
Aspirin on Wikipedia: http://en.wikipedia.org/wiki/Aspirin
Organisms Affected: Humans and other mammals