Aspirin¿¡ ´ëÇÑ Mechanism_Of_Action Á¤º¸ 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¿¡ ´ëÇÑ Pharmacology Á¤º¸ 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.
Protein Binding
Aspirin¿¡ ´ëÇÑ ´Ü¹é°áÇÕ Á¤º¸ High (99.5%) to albumin. Decreases as plasma salicylate concentration increases, with reduced plasma albumin concentration or renal dysfunction, and during pregnancy.
Half-life
Aspirin¿¡ ´ëÇÑ ¹Ý°¨±â Á¤º¸ 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.
Absorption
Aspirin¿¡ ´ëÇÑ Absorption Á¤º¸ 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.
Biotransformation
Aspirin¿¡ ´ëÇÑ Biotransformation Á¤º¸ 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.
Aspirin¿¡ ´ëÇÑ Drug_Interactions Á¤º¸ Acetazolamide The salicylate at high dose increases the effect of the carbonic anyhydraseAcetohexamide The salicylate increases the effect of sulfonylureaMethotrexate The salicylate increases the effect and toxicity of methotrexateAnisindione The salicylate increases effect of anticoagulantBetamethasone The corticosteroid decreases the effect of salicylatesChlorpropamide The salicylate increases the effect of sulfonylureaDexamethasone The corticosteroid decreases the effect of salicylatesDichlorphenamide The salicylate at high dose increases the effect of the carbonic anyhydrase inhibitorsDicumarol The salicylate increases effect of anticoagulantValproic Acid The salicylate increases the effect of valproic acidFludrocortisone The corticosteroid decreases the effect of salicylatesGliclazide The salicylate increases the effect of sulfonylureaGlipizide The salicylate increases the effect of sulfonylureaGlisoxepide The salicylate increases the effect of sulfonylureaGlibenclamide The salicylate increases the effect of sulfonylureaTolazamide The salicylate increases the effect of sulfonylureaTolbutamide The salicylate increases the effect of sulfonylureaGriseofulvin Anticipate decrease of ASA efficiency in presence of griseofulvinHeparin Association of ASA/heparin increases risk of bleedingHydrocortisone The corticosteroid decreases the effect of salicylatesPrednisolone The corticosteroid decreases the effect of salicylatesPrednisone The corticosteroid decreases the effect of salicylatesTriamcinolone The corticosteroid decreases the effect of salicylatesWarfarin The salicylate increases the effect of anticoagulantAcenocoumarol The salicylate increases the effect of anticoagulantMethylprednisolone The corticosteroid decreases the effect of salicylatesIbuprofen Ibuprofen reduces ASA cardioprotective effectsInsulin-aspart The salicylate increases the effect of insulinInsulin-detemir The salicylate increases the effect of insulinInsulin-glargine The salicylate increases the effect of insulinInsulin-glulisine The salicylate increases the effect of insulinInsulin-lispro The salicylate increases the effect of insulinKetorolac ASA increases toxicity of ketorolacMethazolamide The salicylate at high dose increases the effect of the carbonic anhydrase inhibitorsProbenecid The salicylate decreases the uricosuric effect of probenecidSulfinpyrazone The salicylate antagonizes the uricosuric effect of sulfinpyrazoneTiclopidine Increased effect of ticlopidineCortisone acetate The corticosteroid decreases the effect of salicylatesGinkgo biloba Association of ASA/ginkgo increases risk of bleedingGlycodiazine The salicylate increases the effect of sulfonylureaInsulin The salicylate increases the effect of insulinParamethasone The corticosteroid decreases the effect of salicylates
Aspirin¿¡ ´ëÇÑ Food Interaction Á¤º¸ 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.
Aspirin¿¡ ´ëÇÑ Description Á¤º¸ 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)