What is the pharmacokinetics of aspirin?
Pharmacology/Pharmacokinetics Aspirin is rapidly absorbed in the upper gastrointestinal (GI) tract and results in a measurable inhibition of platelet function within 60 minutes. This antiplatelet effect is associated with prolongation of the bleeding time and inhibition of TXA2-dependent platelet aggregation.
What could impact the pharmacokinetics of aspirin?
Clinical implications Concomitant disease, patient age and gender may influence the metabolism of aspirin, and should be considered before determining the dosage regimen. Aspirin should be used cautiously in patients with hepatic impairment because salicylate is essentially metabolized in the liver.
What is the mechanism of action pharmacodynamics of aspirin?
Aspirin causes several different effects in the body, mainly the reduction of inflammation, analgesia (relief of pain), the prevention of clotting, and the reduction of fever. Much of this is believed to be due to decreased production of prostaglandins and TXA2.
How is aspirin metabolized?
Inside the body, aspirin is converted into its active metabolite salicylate. This happens mostly in the liver. Peak concentration of salicylate in the plasma occurs approximately 1-2 hours after ingestion. Excretion from the body is mainly through the kidney.
What is the bioavailability of aspirin?
Oral bioavailability of acetylsalicylic acid is approximately 50% because a fraction of the administered and absorbed dose of the drug is inactivated, that is, deacetylated, by the carboxylesterases in plasma and liver before entering the systemic circulation (first-pass effect).
What is the mechanism of action of aspirin in preventing clotting?
The primary established effect of aspirin on hemostasis is to impair platelet aggregation via inhibition of platelet thromboxane A2 synthesis, thus reducing thrombus formation on the surface of the damaged arterial wall.
What metabolizes aspirin?
Aspirin is metabolized by three key enzymes, UDP-glucuronosyltransferase 1A6 (UGT1A6), cytochrome P450 2C9 (CYP2C9), and N-acetyl transferase 2 (NAT2). Each of these enzymes is known to have genetic polymorphisms.
What is COX-1 and COX-2?
COX-1 is thought to be responsible for the production of prostaglandins associated with normal physiologic function and is found in such tissues as the stomach, kidney, and platelets. COX-2 was thought to be induced as the result of inflammation and responsible for producing prostaglandins such as prostaglandin E2.
Why aspirin is absorbed in the stomach?
Aspirin is readily soluble in basic medium; as a result, it is quickly digested in the small intestine by inactively intermingling with the body fluid and bio transformed to salicylate in the liver and intestine [6; 10].
What happens to aspirin in the liver?
Aspirin can cause several forms of liver injury: in high doses, aspirin can cause moderate to marked serum aminotransferase elevations occasionally with jaundice or signs of liver dysfunction, and in lower doses in susceptible children with a febrile illness aspirin can lead to Reye syndrome.
What is the half-life of aspirin?
The plasma half-life of aspirin is only 20 min in circulating blood. It is rapidly deacetylated and converted to salicylate in vivo. Salicylate does not affect COX-1 or COX-2 activity . Because platelets cannot generate new COX, the effects of aspirin last for the duration of the life of the platelet [10 days].
Why aspirin is used as prodrug?
Aspirin was originally considered a prodrug to salicylic acid since it was at that time thought to have the same pharmacodynamic effects as salicylic acid and is rapidly transformed to it in vivo. Later aspirin was also found to be effective in its own right.
Clinical pharmacokinetics of aspirin Aspirin is very rapidly absorbed from the gastrointestinal tract when administered as a solution, and somewhat more slowly when administered in tablets. It is rapidly hydrolyzed in the body to salicylic acid; the plasma concentration of the latter must be maintained within a relatively narrow range …
The half-life of aspirin is only 15 to 20 minutes. Half-life is the amount of time it takes to decrease the concentration of the drug in your body by half. Once the aspirin is broken down into salicylic acid, the salicylic acid has a half-life of six hours. In higher doses, the half-life increases,…
Therefore, aspirin has a very short half-life. Salicylate, in turn, is mainly metabolized by the liver. This metabolism occurs primarily by hepatic conjugation with glycin or glucuronic acid, each involving different metabolic pathways. The predominant pathway is the conjugation with glycin, which is saturable.
What does aspirin inhibit?
Aspirin inhibits the action of enzymes in the body to achieve these results. Aspirin inhibits prostaglandin synthesis, which results in its analgesic effects. Prostaglandins are a substance similar to hormones that affect different body functions.