Brand Name: Damason
Generic Name: Aspirin

ASA interferes with the production of prostaglandins in various organs and tissues through acetylation of the enzyme cyclo-oxygenase. Prostaglandins are themselves powerful irritants and produce headaches and pain on injection in man. Prostaglandins also appear to sensitize pain receptors to other noxious substances such as histamine and bradykinin. By preventing the synthesis and release of prostaglandins in inflammation, ASA may avert the sensitization of pain receptors.

The antipyretic activity of ASA is due to its ability to interfere with the production of prostaglandin E₁ in the brain. Prostaglandin E₁ is one of the most powerful pyretic agents known.

The inhibition of platelet aggregation by ASA is due to its ability to interfere with the production of thromboxane A₂ within the platelet. Thromboxane A₂ is largely responsible for the aggregating properties of platelets.

When ASA is taken orally, it is rapidly absorbed from the stomach and proximal small intestine. The gastric mucosa is permeable to the nonionized form of ASA, which passes through the stomach wall by a passive diffusion process.

Optimum absorption of salicylate in the human stomach occurs in the pH range of 2.15 to 4.10. Absorption in the small intestine occurs at a significantly faster rate than in the stomach. After an oral dose of 650 mg Aspirin, the plasma acetylsalicylate concentration in man usually reaches a level between 0.6 and 1.0 mg% in 20 minutes after ingestion and drops to 0.2 mg% within an hour. Within the same period of time, half or more of the ingested dose is hydrolyzed to salicylic acid by esterases in the gastrointestinal mucosa and the liver, the total plasma salicylate concentration reaching a peak between 1 or 2 hours after ingestion, averaging between 3 and 7 mg%. Many factors influence the speed of absorption of ASA in a particular individual at a given time; tablet disintegration, solubility, particle size, gastric emptying time, psychological state, physical condition, nature and quantity of gastric contents, etc., all affect absorption.

Distribution of salicylate throughout most body fluids and tissues proceeds at a rapid rate after absorption. Aside from the plasma itself, fluids which have been found to contain substantial amounts of salicylate after oral ingestion include spinal, peritoneal and synovial fluids, saliva and milk. Tissues containing high concentrations of the drug are the kidney, liver, heart and lungs. Concentrations in the brain are usually low, and are minimal in feces, bile and sweat.

The drug readily crosses the placental barrier. At clinical concentrations, from 50% to 90% of the salicylate is bound to plasma proteins especially albumin, while ASA itself is bound to only a very limited extent. However, ASA has the capacity of acetylating various proteins, hormones, DNA, platelets and hemoglobin, which at least partly explains its wide-ranging pharmacological actions.

The liver appears to be the principal site for salicylate metabolism, although other tissues may also be involved. The three chief metabolic products of salicylic acid are salicyluric acid, the ether or phenolic glucuronide and the ester or acyl glucuronide. A small fraction is also converted to gentisic acid and other hydroxybenzoic acids. The half-life of ASA in the circulation is from 13 to 19 minutes so that the blood level drops quickly after absorption is complete. However, the half-life of the salicylate ranges between 3.5 and 4.5 hours, which means that 50% of the ingested dose leaves the circulation within that time.

Excretion of salicylates occurs principally via the kidney, through a combination of glomerular filtration and tubular excretion, in the form of free salicylic acid, salicyluric acid, as well as phenolic and acyl glucuronides. Salicylate can be detected in the urine shortly after its ingestion but the full dose requires up to 48 hours for complete elimination. The rate of excretion of free salicylate is extremely variable, reported recovery rates in human urine ranging from 10% to 85%, depending largely on urinary pH. In general, it can be stated that acid urine facilitates reabsorption of salicylate by renal tubules, while alkaline urine promotes excretion of the drug.