Acetylsalicylic acid
(ASA, Aspirin)

Acetylsalicylic acid (ah-SEE-till-sal-ih-SILL-ick AH-sid)

ASA

Aspirin

Classification: Nonnarcotic analgesic, antipyretic, anti-inflammatory agent

Action/Kinetics: Exhibits antipyretic, anti-inflammatory, and analgesic effects. The antipyretic effect is due to an action on the hypothalamus, resulting in heat loss by vasodilation of peripheral blood vessels and promoting sweating. Prostaglandins have been implicated in the inflammatory process, as well as in mediation of pain. Thus, if levels are decreased, the inflammatory reaction may subside. The anti-inflammatory effects are probably mediated through inhibition of cyclo-oxygenase, which results in a decrease in prostaglandin synthesis and other mediators of the pain response. The mechanism of action for the analgesic effects of aspirin is not known fully but is partly attributable to improvement of the inflammatory condition. Aspirin also produces inhibition of platelet aggregation by decreasing the synthesis of endoperoxides and thromboxanes--substances that mediate platelet aggregation.  Large doses of aspirin (5 g/day or more) increase uric acid secretion, while low doses (2 g/day or less) decrease uric acid secretion. However, aspirin antagonizes drugs used to treat gout.

Rapidly absorbed after PO administration. Is hydrolyzed to the active salicylic acid, which is 70%-90% protein bound. For arthritis and rheumatic disease, blood levels of 150-300 mcg/mL should be maintained. For analgesic and antipyretic, achieve blood levels of 25-50 mcg/mL. For acute rheumatic fever, achieve blood levels of 150-300 mcg/mL. Therapeutic salicylic acid serum levels: 150-300 mcg/mL, although tinnitus occurs at serum levels above 200 mcg/mL and serious toxicity above 400 mcg/mL. t1/2: aspirin, 15-20 min; salicylic acid, 2-20 hr, depending on the dose. Salicylic acid and metabolites are excreted by the kidney. The bioavailability of enteric-coated salicylate products may be poor. The addition of antacids (buffered aspirin) may decrease GI irritation and increase the dissolution and absorption of such products.

Uses: Analgesic: Pain arising from integumental structures, myalgias, neuralgias, arthralgias, headache, dysmenorrhea, and similar types of pain. Antipyretic. Anti-Inflammatory: Arthritis, osteoarthritis, SLE, acute rheumatic fever, gout, and many other conditions. Mucocutaneous lymph node syndrome (Kawasaki disease). Cardiovascular: Reduce risk of death and nonfatal stroke in those who have had an ischemic stroke or TIA; also combined with dipyridamole for this purpose. Reduce risk of vascular mortality with suspected acute MI. Reduce the combined risk of recurrent MI and death after an MI or unstable angina. Reduce risk of MI and sudden death in chronic stable angina. Pre-existing need for aspirin following coronary artery bypass grafting, percutaneous transluminal coronary angioplasty, or carotid endarterectomy. Gout. May be effective in less severe postoperative and postpartum pain; pain secondary to trauma and cancer. Investigational: Chronic use to prevent cataract formation; low doses to prevent toxemia of pregnancy; in pregnant women with inadequate uteroplacental blood flow. Reduce colon cancer mortality (low doses). Low doses of aspirin and warfarin to reduce the risk of a second heart attack.

Contraindications: Hypersensitivity to salicylates. Clients with asthma, hay fever, or nasal polyps have a higher incidence of hypersensitivity reactions. Severe anemia, history of blood coagulation defects, in conjunction with anticoagulant therapy. Salicylates can cause congestive failure when taken in the large doses used for rheumatic diseases. Vitamin K deficiency; 1 week before and after surgery. In pregnancy, especially the last trimester as the drug may cause problems in the newborn child or complications during delivery. In children or teenagers with chicken-pox or flu due to possibility of development of Reye's syndrome.
Controlled-release aspirin is not recommended for use as an antipyretic or short-term analgesic because adequate blood levels may not be reached. Also, controlled-release products are not recommended for children less than 12 years of age and in children with fever accompanied by dehydration.

Special Concerns: Use with caution during lactation and in the presence of gastric or peptic ulcers, in mild diabetes, erosive gastritis, bleeding tendencies, in cardiac disease, and in liver or kidney disease. Aspirin products now carry the following labeling: ``It is especially important not to use aspirin during the last three months of pregnancy unless specifically directed to do so by a doctor because it may cause problems in the newborn child or complications during delivery.''

Side Effects: The toxic effects of the salicylates are dose-related. GI: Dyspepsia, heartburn, anorexia, nausea, occult blood loss, epigastric discomfort, massive GI bleeding, potentiation of peptic ulcer. Possible stomach bleeding in those who ingest three or more alcoholic drinks/day. Allergic: Bronchospasm, asthma-like symptoms, anaphylaxis skin rashes, angioedema, urticaria, rhinitis, and nasal polyps. Hematologic: Prolongation of bleeding time, thrombocytopenia, leukopenia, purpura, shortened erythrocyte survival time, decreased plasma iron levels. Miscellaneous: Thirst, fever, dimness of vision.
NOTE: Use of aspirin in children and teenagers with flu or chickenpox may result in the development of Reye's syndrome. Also, dehydrated, febrile children are more prone to salicylate intoxication.

Laboratory Test Alterations: False + or increase: Amylase, AST, ALT, uric acid, PBI, urinary VMA (most tests), catecholamines, urinary glucose (Benedict's, Clinitest), and urinary uric acid (at high doses) values. False ñ or decreased: CO₂ content, glucose (fasting), potassium, urinary VMA (Pisano method), and thrombocyte values.

Overdose Management: Symptoms of Mild Salicylate Toxicity (Salicylism): At serum levels between 150 and 200 mcg/mL. GI: N&V, diarrhea, thirst. CNS: Tinnitus (most common), dizziness, difficulty in hearing, mental confusion, lassitude. Miscellaneous: Flushing, sweating, tachycardia. Symptoms of salicylism may be observed with doses used for inflammatory disease or rheumatic fever. Symptoms of Severe Salicylate Poisoning: At serum levels over 400 mcg/mL. CNS: Excitement, confusion, disorientation, irritability, hallucinations, lethargy, stupor, coma, respiratory failure, seizures. Metabolic: Respiratory alkalosis (initially), respiratory acidosis and metabolic acidosis, dehydration. GI: N&V. Hematologic: Platelet dysfunction, hypoprothrombinemia, increased capillary fragility. Miscellaneous: Hyperthermia, hemorrhage, CV collapse, renal failure hyperventilation, pulmonary edema, tetany, hypoglycemia (late). Treatment (Toxicity):

1. If the client has had repeated administration of large doses of salicylates, document and report evidence of hyperventilation or complaints of auditory or visual disturbances (symptoms of salicylism).

2. Severe salicylate poisoning, whether due to overdose or accumulation, will have an exaggerated effect on the CNS and the metabolic system: Clients may develop a salicylate jag characterized by garrulous behavior. They may act as if they were inebriated. Convulsions and coma may follow.

3. When working with febrile children or the elderly who have been treated with aspirin, maintain adequate fluid intake. These clients are more susceptible to salicylate intoxication if they are dehydrated.

4. The following treatment approaches may be considered for treatment of acute salicylate toxicity: Initially induce vomiting or perform gastric lavage followed by activated charcoal (most effective if given within 2 hr of ingestion). Monitor salicylate levels and acid-base and fluid and electrolyte balance. If required, administer IV solutions of dextrose, saline, potassium, and sodium bicarbonate as well as vitamin K. Seizures may be treated with diazepam. Treat hyperthermia if present. Alkaline diuresis will enhance renal excretion. Hemodialysis is effective but should be reserved for severe poisonings. If necessary, administer oxygen and artificial ventilation

Drug Interactions: Acetazolamide / ↑ CNS toxicity of salicylates; also, ↑ excretion of salicylic acid if urine kept alkaline Alcohol, ethyl /Ý ↑ Chance of GI bleeding caused by salicylates Alteplase, recombinant / ↑Ý Risk of bleeding PAS / Possible ↑ effect of PAS due to ↓ excretion by kidney or ↓ plasma protein binding Ammonium chloride / ↑Ý Effect of salicylates by ↑Ý renal tubular reabsorption ACE inhibitors / Ý↓ Effect of ACE inhibitors possibly due to prostaglandin inhibition Antacids / Ý↓ Salicylate levels in plasma due toÝ ↑ rate of renal excretion Anticoagulants, oral / ↑Ý Effect of anticoagulant by Ý↓ plasma protein binding and plasma prothrombin Antirheumatics / Both are ulcerogenic and may cause Ý↓ GI bleeding Ascorbic acid / ↑Ý Effect of salicylates by ↑ renal tubular reabsorption Beta-adrenergic blocking agents / Salicylates Ý↓ action of beta-blockers, possibly due to prostaglandin inhibition Charcoal, activated / Ý↓ Absorption of salicylates from GI tract Corticosteroids / Both are ulcerogenic; also, corticosteroids may Ý↓ blood salicylate levels by ↑ breakdown by liver and ↑ excretion Dipyridamole / Additive anticoagulant effects Feverfew / Potential for ↑ antiplatelet effect Furosemide / ↑ Chance of salicylate toxicity due to Ý↓ renal excretion; also, salicylates may Ý↓ effect of furosemide in clients with impaired renal function or cirrhosis with ascites Garlic / Potential for ↑ antiplatelet effect Ginkgo biloba / Potential forÝ ↑ effect on platelet aggregation Ginseng / Potential for Ý↓ effect on platelet aggregation Heparin / Inhibition of platelet adhesiveness by aspirin may result in bleeding tendencies Hypoglycemics, oral / ↑ Hypoglycemia R/T Ý↓ plasma protein binding and Ý↓ excretion Indomethacin / Both are ulcerogenic and may causeÝ ↑ GI bleeding Insulin / Salicylates ↑ hypoglycemic effect of insulin Methionine / ↑ Effect of salicylates by Ý↓ renal tubular reabsorption Methotrexate / ↑ Methotrexate effect by Ý↓ plasma protein binding; also, salicylates block drugs' renal excretion Nitroglycerin / Combination may result in unexpected hypotension Nizatidine / ↑ Serum levels of salicylates NSAIDs / Additive ulcerogenic effects; also, aspirin may Ý↓ serum levels of NSAIDs Phenylbutazone / Combination may produce hyperuricemia Phenytoin /Ý ↑ Phenytoin effect by Ý↓ plasma protein binding Probenecid / Salicylates inhibit uricosuric activity of probenecid Sodium bicarbonate / Ý↓ Effect of salicylates by ↑ rate of excretion Spironolactone / Aspirin Ý↓ diuretic drug effect Sulfinpyrazone / Salicylates inhibit uricosuric drug activity Sulfonamides / ↑ Sulfonamides effect by ↑ salicylate blood levels Valproic acid /Ý ↑ Valproic effect R/T Ý↓ plasma protein binding

How Supplied: Chew tablet: 80 mg, 81 mg; Enteric coated tablet: 81 mg, 162 mg, 324 mg, 325 mg, 500 mg, 650 mg, 975 mg; Gum: 227 mg; Suppository: 60 mg, 120 mg, 125 mg, 200 mg, 300 mg, 325 mg, 600 mg, 650 mg; Tablet: 81 mg, 324 mg, 325 mg, 486 mg, 500 mg, 650 mg; Tablet, Extended Release: 650 mg, 800 mg

Dosage
ïGum, Chewable Tablets, Coated Tablets, Effervescent Tablets, Enteric-Coated Tablets, Suppositories, Tablets, Timed (Controlled) Release Tablets Analgesic, antipyretic.
Adults: 325-500 mg q 3 hr, 325-600 mg q 4 hr, or 650-1,000 mg q 6 hr. As an alternative, the adult chewable tablet (81 mg each) may be used in doses of 4-8 tablets q 4 hr as needed. Pediatric: 65 mg/kg/day (alternate dose: 1.5 g/m²/day) in divided doses q 4-6 hr, not to exceed 3.6 g/day. Alternatively, the following dosage regimen can be used: Pediatric, 2-3 years: 162 mg q 4 hr as needed; 4-5 years: 243 mg q 4 hr as needed; 6-8 years: 320-325 mg q 4 hr as needed; 9-10 years: 405 mg q 4 hr as needed; 11 years: 486 mg q 4 hr as needed; 12-14 years: 648 mg q 4 hr.
Arthritis, rheumatic diseases.
Adults: 3.2-6 g/day in divided doses.
Juvenile rheumatoid arthritis.
60-110 mg/kg/day (alternate dose: 3 g/m²) in divided doses q 6-8 hr. When initiating therapy at 60 mg/kg/day, dose may be increased by 20 mg/kg/day after 5-7 days and by 10 mg/kg/day after another 5-7 days.
Acute rheumatic fever.
Adults, initial: 5-8 g/day. Pediatric, initial: 100 mg/kg/day (3 g/m²/day) for 2 weeks; then, decrease to 75 mg/kg/day for 4-6 weeks.
Reduce risk of death and nonfatal stroke following ischemic stroke or TIA
50-325 mg/day.
Reduce risk of vascular mortality in suspected acute MI.
160-162.5 mg immediately and then daily for 30 days. Consider subsequent prophylactic therapy.
Reduce combined risk of recurrent MI and death in those with a previous MI or unstable angina or to reduce risk of MI and sudden death in those with chronic stable angina.
75-325 mg/day.
Pre-existing need for aspirin following coronary artery bypass grafting, percutaneous transluminal coronary angioplasty, carotid endarterectomy.
Dosage varies by procedure.
Kawasaki disease.
Adults: 80-180 mg/kg/day during the febrile period. After the fever resolves, the dose may be adjusted to 10 mg/kg/day.
NOTE: Aspirin Regimen Bayer 81 mg with Calcium contains 250 mg calcium carbonate (10% of RDA) and 81 mg of acetylsalicylic acid for individuals who require aspirin to prevent recurrent heart attacks and strokes.