Aspirin action

The hydrophobic domains of some integral membrane proteins penetrate only one leaflet of the bilayer. Cyclooxygenase, the target of aspirin action, is an example its hydrophobic helices do not span the whole membrane but interact strongly with the acyl groups on one side of the bilayer (see Box 21-2, Fig. la). 

Aspirin covalently modifies COX-1 and COX-2, irreversibly inhibiting COX activity. This is an important distinction from all the NSAIDs because the duration of aspirin s effects is related to the turnover rate of COX in different target tissues. The duration of effect of nonaspirin NSAIDs, which competitively inhibit the active sites of the COX enzymes, relates more directly to the time course of drug disposition. The importance of enzyme turnover in relief from aspirin action is most notable in platelets, which, being anucleate, have a markedly limited capacity for protein synthesis. Thus, the consequences of inhibition of platelet COX (COX-1) last for the lifetime of the platelet. Inhibition of platelet COX-1-dependent TXA formation, therefore, is cumulative with repeated doses of aspirin (at least as low as 30 mg/day) and takes roughly 8-12 days (the platelet turnover time) to recover once therapy has been stopped. 

Although aspirin and sallcyclic acid exhibit half-lives in man of only 13 to 19 min. and 3.5 to 4.5 hrs., respectively,31 the effect of aspirin on platelets Iji vivo has a duration which approximately parallels platelet survival time of 2-7 days. The currently accepted hypothesis to explain this action holds that aspirin Irreversibly alters platelet function by acetylation of a protein component of platelet membrane. A substantial amount of experimental evidence consistent with this hypothesis has accumulated.1 32 Although aspirin does not inhibit ADP-induced aggregation its effect on the release reaction decreases platelet response and abolishes the "second wave" of aggregation in the presence of ADP. It appears that another component of aspirin action is an effect on a plasma cofactor of ADP-induced aggregation.33,34 Evidence has been... 

Standards for dmg chemicals are pubUshed ia USP—NE. Dmg substances are chemicals that have therapeutic or diagnostic uses, whereas pharmaceutical iagredients provide preservative action, fiavoiing, or hilfillment of a function ia the formulation of dosage-form dmgs. Examples of dmg substances are acetaminophen [103-90-2] ampicillin [69-53-4] aspirin [50-78-2] powdered ipecac, riboflavin [83-88-5] staimous fluoride [7783-47-3] and thyroid. Examples of pharmaceutical iagredients are ethylparaben [120-47-8] lactose [63-42-3] magnesium stearate [557-04-0] sodium hydroxide [1310-73-2] starch [9005-25-8] and vanillin [121-33-5],... 

These actions of aspirin are thought to result from its abiHty to reduce the production of prostaglandin formed by platelet cells without appreciably... 

The understanding of these actions of aspirin started in 1971 (45) and resulted in the recommendations of the medical community that small doses of aspirin, used under the care of the doctor, may be a prevention measure for heart attack, and stroke for those considered at risk in the population. Further reported work may expand health benefits to prevention of certain kinds of cancer (46). 

Some of these indazoles showed analgesic activity greater than that of aspirin and several possessed significant antiinflammatory action. Both properties were the most striking and characteristic ones of the series. In a few cases the authors isolated the corresponding indazolones (705) which were less active than (704) in terms of analgesic and antiinflammatory properties. 

There are thought to be at least four different mechanisms of action for NSAIDs. Aspirin (and also bromoaspirin) covalently... 

The popularity of aspirin has led to the preparation of a liost of relatively simple derivatives in the hope of finding a ilrug that would be either superior in action or better tolerated. i alicylamide (5), for example, is sometimes prescribed for pa-I Lents allergic to aspirin. It should be noted, however, that I his agent is not as active as the parent compound as an antiinflammatory or analgesic agent. This may be related to the fact I hat salicylamide does not undergo conversion to salicylic acid i 11 the body. 

The action of polyethylenimine on the hydrolyses of 43 (aspirin) was characteristic95 the reaction was substantially increased, passing through a maximum at pH = 7.8, where the rate constant was 1300 times greater than in the absence of the polyelectrolyte. 

Aspirin is the brand name of acetylsalicylic acid. It is the most widely used analgesic, antipyretic and antiinflammatory diug. Its main mode of action is iireversible acetylation of cyclooxygenases. 

Vane JR (1971) Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nat New Biol 231 232-235... 

There are several hundred reported NF-kB inhibitors (see www.nf-kb.org for a complete and updated list). These inhibitors include natural products, chemicals, metabolites, and synthetic compounds. A large majority of these products, in particular commonly used antiinflammatory drugs such as corticosteroids and the nonsteroidal antiinflammatory drugs (NSADDs) aspirin, sulindac, ibuprofen and sulphasalazine, have the ability to partially inhibit NF-kB activity in cell culture. However, the precise mechanism of action and the specific molecular targets of most of these inhibitors remain unclear. 

Kashfi, K. Rigas, B. The mechanism of action of nitric oxide-donating aspirin. Biochem. Biophys. Res. Commun. 2007, 358, 1096-1101. 

Aspirin, non-acetylated salicylates, and other NSAIDs have analgesic, antipyretic, and anti-inflammatory actions. These agents inhibit cyclooxygenase (COX-1 and COX-2) enzymes, thereby preventing prostaglandin synthesis, which results in reduced nociceptor sensitization and an increased pain threshold. NSAIDs are the preferred agents for mild to moderate pain in situations that are mediated by prostaglandins (e.g., rheumatoid... 

Aspirin desensitization is useful in diseases where low-level antiplatelet action is needed and in the care of patients with aspirin sensitivity and intractable nasal polyps. Lysine aspirin availability in Europe allows desensitization by inhalation at... 

Probenecid is a uricosuric agent that blocks the tubular reabsorption of uric acid, increasing its excretion. Because of its mechanism of action, probenecid is contraindicated in patients with a history of uric acid stones or nephropathy. Probenecid loses its effectiveness as renal function declines and should be avoided when the creatinine clearance is 50 mL/minute or less. Its uricosuric effect is counteracted by low aspirin doses, which many patients receive for prophylaxis of coronary heart disease. 

Each Alka-Seltzer tablet contains 1916 mg of sodium bicarbonate, 1000 mg of citric acid (Fig. 9.1.2), and 325 mg of aspirin or acetylsalicylic acid (Fig. 9.1.3). Bromo Seltzer also contains sodium bicarbonate and citric acid as well as acetaminophen (Fig. 9.1.4). Several equilibria describe the action of bicarbonate-based antacid tablets. First of all, sodium bicarbonate dissolves completely in aqueous solution to generate sodium ions and bicarbonate ions ... 

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