Analgesic – Anti-inflammatory –
Antipyretic – Platelet Aggregation Inhibitor
Action And Clinical Pharmacology: 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 non-ionized 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 Aspirin 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.
Indications And Clinical Uses: The relief of pain, fever and inflammation of a variety of conditions such as influenza, common cold, low back and neck pain, dysmenorrhea, headache, toothache, sprains and strains, myositis, neuralgia, synovitis, arthritis, bursitis, burns, injuries, following surgical and dental procedures.
ASA is also indicated for the following uses, based on its platelet aggregation inhibitory properties:
For reducing the risk of morbidity and death in patients with unstable angina and in those with previous myocardial infarction.
For reducing the risk of transient ischemic attacks (TIA) and for secondary prevention of atherothrombotic cerebral infarction.
Prophylaxis of venous thromboembolism after total hip replacement in men.
Reduction in the adhesive properties of the platelets in patients following carotid endarterectomy to prevent recurrence of TIA and in hemodialysis patients with a silicone rubber arteriovenous cannula.
Contra-Indications: Salicylate sensitivity, active peptic ulcer.
Manufacturers’ Warnings In Clinical States: ASA is one of the most frequent causes of accidental poisonings in toddlers and infants. Tablets should be kept well out of the reach of children.
A possible association between Reye’s syndrome and the use of salicylates has been suggested but not established. Reye’s syndrome has also occurred in many patients not exposed to salicylates. However, caution is advised when prescribing salicylate-containing medications for children and teenagers with influenza or chickenpox.
Precautions: Salicylates should be administered cautiously to patients with asthma and other allergic conditions, a history of gastrointestinal ulcerations, bleeding tendencies, significant anemia or hypoprothrombinemia.
Patients taking ASA daily are at an increased risk of developing gastrointestinal bleeding following the ingestion of alcohol.
Caution is necessary when salicylates and anticoagulants are prescribed concurrently, as salicylates can depress the concentration of prothrombin in the plasma.
Diabetics receiving concurrent salicylate-hypoglycemic therapy should be monitored closely: reduction of the sulfonylurea hypoglycemic drug dosage may be necessary; insulin requirements may change.
Pregnancy: High doses (3 g daily) of ASA during pregnancy may lengthen the gestation and parturition time.
Salicylates can produce changes in thyroid function tests.
Sodium excretion produced by spironolactone may be decreased by salicylate administration.
Salicylates in large doses are uricosuric agents, smaller amounts may depress uric acid clearance and thus decrease the uricosuric effects of other drugs.
Salicylates also retard the renal elimination of methotrexate.
Adverse Reactions: Gastrointestinal: (the frequency and severity of these adverse effects are dose related) nausea, vomiting, diarrhea, gastrointestinal bleeding and/or ulceration, dyspepsia, heartburn.
Ear: tinnitus, vertigo, hearing loss.
Hematologic: leukopenia, thrombocytopenia, purpura, anemia.
Dermatologic and hypersensitivity: urticaria, angioedema, pruritus, skin eruptions, asthma, anaphylaxis.
Miscellaneous: mental confusion, drowsiness, sweating, thirst.
Symptoms And Treatment Of Overdose: Symptoms: In mild overdosage these may include rapid and deep breathing, nausea, vomiting, vertigo, tinnitus, flushing, sweating, thirst and tachycardia. In more severe cases, acid-base disturbances including respiratory alkalosis and metabolic acidosis can occur. Severe cases may show fever, hemorrhage, excitement, confusion, convulsions or coma and respiratory failure.
Treatment: Treatment consists of prevention and management of acid-base and fluid and electrolyte disturbances. Renal clearance is increased by increasing urine flow and by alkaline diuresis but care must be taken in this approach to not further aggravate metabolic acidosis and hypokalemia. Acidemia should be prevented by administration of adequate sodium containing fluids and sodium bicarbonate. Hypoglycemia is an occasional accompaniment of salicylate overdosage and can be managed by glucose solutions. If a hemorrhagic diathesis is evident, give vitamin K. Hemodialysis may be useful in complex acid base disturbances particularly in the presence of abnormal renal function.
Dosage And Administration: Analgesic and Antipyretic: Adults: 1 to 2 tablets (325 to 650 mg) orally every 4 hours. Children under 12: 10 to 15 mg/kg every 6 hours, not to exceed total daily dose of 2.4 g.
Anti-inflammatory: Adults: 3 tablets (975 mg) 4 to 6 times a day, up to 30 tablets daily, may be required for optimal anti-inflammatory effect. A blood level between 15 and 30 mg/100 mL is in the desirable therapeutic range.
Children: 60 to 125 mg/kg daily in 4 to 6 divided doses.
For reducing the risk of morbidity and death in patients with unstable angina and in those with previous myocardial infarction: 80 to 325 mg daily according to the individual needs of the patient, as determined by the physician. Coated Aspirin Daily Low Dose is specifically indicated for these uses.
For reducing the risk of transient ischemic attacks (TIA) and for secondary prevention of atherothrombotic cerebral infarction: 80 to 325 mg daily according to the individual needs of the patient, as determined by the physician. Coated Aspirin Daily Low Dose is specifically indicated for these uses.
For prophylaxis of venous thromboembolism after total hip replacement: 650 mg twice a day (1 300 mg daily), started 1 day before surgery and continued for 14 days.
For other platelet aggregation inhibitory uses: 325 to 1 300 mg daily according to individual needs and generally accepted standards of care for each indication.
Availability And Storage: Tablets: 325 mg: Each white tablet with the Bayer Cross on both sides contains: ASA 325 mg USP. Nonmedicinal ingredients: cornstarch, FD&C Blue #2, hydroxypropyl methylcellulose, potassium sorbate, titanium dioxide, triacetin and xanthan gum. Energy: 1.4 kJ (0.336 kcal). Alcohol-, lactose-, paraben-, sodium-, sulfite- and tartrazine-free. Packages of 12, 24, 50, 100 and 200.
Extra Strength, 500 mg: Each white tablet with the Bayer Cross in red ink on one side contains: ASA 500 mg USP. Nonmedicinal ingredients: cornstarch, D&C Red #7, FD&C Blue #2, FD&C Red #40, hydroxypropyl methylcellulose, titanium dioxide and triacetin. Energy: 2.18 kJ (0.52 kcal). Alcohol-, lactose-, paraben-, sodium-, sulfite- and tartrazine-free. Packages of 30, 60 and 100.
Caplets: Each white capsule-shaped tablet (caplet) with Bayer on one side and score on the other, contains: ASA 325 mg. Nonmedicinal ingredients: cornstarch, FD&C Blue #2, hydroxypropyl methylcellulose, potassium sorbate, titanium dioxide, triacetin and xanthan gum. Alcohol-, lactose-, parabens-, sodium-, sulfite- and tartrazine-free. Packages of 50 and 100.
Children’s Size Aspirin Tablets: Each peach colored tablet, with a pleasant orange taste, with Bayer Cross on one side and Aspirin on the other, contains: ASA 80 mg USP. Nonmedicinal ingredients: cornstarch, dextrose, FD&C Yellow #6, orange juice flavor and sodium cyclamate. Energy: 2.24 kJ (0.537 kcal).
Coated Aspirin Daily Low Dose: Each pale blue colored enteric coated tablet, with 81 in dark blue ink on one side, contains: ASA 81 mg. Alcohol-, paraben-, sulfite- and tartrazine-free. Bottles of 24 and 120.
ASPIRINÂ® Bayer Consumer ASA Analgesic – Anti-inflammatory – Antipyretic – Platelet Aggregation Inhibitor