Salicylic Acid – Indications, Contraindications

Salicylates have been available since the early 1900s. This activity outlines the indications, mechanism of action, methods of administration, important adverse effects, contraindications, and monitoring, of salicylic acid, so providers can direct patient therapy in treating indicated conditions as part of the interprofessional team.

Salicylates have been derived from the willow tree bark. The Sumerians were noted to have used remedies derived from the willow tree for pain management as far back as 4000 years ago. Hippocrates used it for managing pain and fever. He even utilized tea brewed from it for pain management during childbirth.

In a 1763 clinical trial, the first of its kind, Reverend Edward Stone studied the effects of willow bark powder for treating fever. About a 100 years later the effects of the willow bark powder were studied for acute rheumatism.

In 1828, Professor Johann Buchner used salicin, the Latin word for willow. Henri Leroux used it to treat rheumatism after isolating it in a crystalline form in 1829. In the 1800s, the Heyden Chemical Company was the first to mass-produce salicylic acid commercially. It was not until 1899 when a modified version by the name of acetylsalicylic acid was registered and marketed by Bayer under the trade name aspirin.

Even though it has been available since the early 1900s, its real mode of action was not known until the late 1970s.

Indications

Some of the indications for aspirin use are as follows

• Key additive in many skin-care products for the treatment of acne, psoriasis, calluses, corns, keratosis pilaris, and warts.
• Angina pectoris
• Angina pectoris prophylaxis
• Ankylosing spondylitis
• Cardiovascular risk reduction
• Colorectal cancer
• Fever
• Ischemic stroke
• Ischemic stroke: Prophylaxis
• Myocardial infarction
• Myocardial infarction: Prophylaxis
• Osteoarthritis
• Pain
• Revascularization procedures: Prophylaxis
• Rheumatoid arthritis
• Systemic lupus erythematosus

Contraindications

• People who are allergic to ibuprofen should not take aspirin as there is cross-reactivity. Patients who have asthma should be cautious if they have asthma or known bronchospasm associated with NSAIDs.
• Aspirin increases the risk of GI bleeding in patients who already suffer from peptic ulcer disease or gastritis. The risk of bleeding is still present even without these conditions if there is concomitant consumption of alcohol or if the patient is on warfarin. Patients who have inborn coagulopathies such as hemophilia should avoid all salicylates. Acquired diathesis as in the setting of dengue or yellow hemorrhagic fever should avoid the use of aspirin.
• Patients who have glucose-6-phosphate dehydrogenase deficiency are at risk of acute intravascular hemolytic anemia. Many factors can precipitate these hemolytic episodes. Aspirin is one such know cause.
• Avoid using aspirin in children who are suffering from a viral infection to avoid Reye syndrome.

Dosage

Therapeutic Index and Toxic Doses 

• Therapeutic drug levels for aspirin are 150 to 300 mcg/mL (salicylate).
• Toxic Levels: Greater than 300 mcg/mL
• Timing: 1 to 3 hours after the dose
• Time to Steady State: 5 to 7 days
• Plasma levels of aspirin can range from 3 to 10 mg/dL for therapeutic doses to as high as 70 to 140 mg/dL for acute toxicity. Due to delayed absorption of certain preparations, levels should be checked 4 hours after consumption and every 2 hours after that until maximum levels are reached.

Treatment needs to be individualized based on symptomatology as well as levels. Aspirin levels do not need to be monitored in most cases. For certain diseases, serum creatinine at baseline, along with serum drug levels if patients have adult or juvenile rheumatoid arthritis, Kawasaki disease, or arthritis/pleurisy.

Aspirin can be administered via the oral, rectal, and intravenous (IV) route.

It is available in different doses, the lowest being 81 mg also called a baby aspirin.

• Tablet: 325 mg, 500 mg
• Delayed-release tablet: 81 mg, 325 mg, 500 mg, 650 mg
• Chewable: 81 mg
• Suppository: 60 mg, 120 mg, 200 mg, 300 mg, 600 mg
• Intravenous: 250 mg, 500 mg

Pharmacokinetics

Aspirin absorption from the gastrointestinal (GI) tract depends on the formulation state. When consumed as a liquid preparation, it is rapidly absorbed as opposed to tablets. Its hydrolysis yields salicylic acid. Salicylic acid has a narrow therapeutic window. If maintained within that narrow range, it provides the appropriate anti-inflammatory effect.

Aspirins absorption is pH sensitive at the level of the small intestine. Absorption is higher through the small intestine than the stomach for the same pH range. At pH 3.5 or 6.5, aspirin’s intestinal absorption is greater than the gastric absorption of the compound. The stomach does not absorb aspirin at pH 6.5.

Salicylate elimination occurs through two pathways via the creation of salicylic acid and salicyl phenolic glucuronide. Salicylic acid is really cleared which can be increased by raising the urinary pH. Medications like antacids can increase renal clearance as they raise urinary pH. It can cross the blood-placental barrier. It is also expressed in breast milk.

Pharmacodynamics

Almost 90% of COX inhibition can be achieved with the administration of 160 to 325 mg of aspirin. These effects last for about 7 to 10 days which usually correspond with the lifespan of a platelet. Prostacyclin inhibition can be achieved with the use of higher doses. This inhibition occurs in the endothelial cells of blood vessels.

Pregnancy and lactation

• No information is available on the clinical use of salicylic acid on the skin during breastfeeding. Because it is unlikely to be appreciably absorbed or appear in breastmilk, it is considered safe to use during breastfeeding. Avoid application to areas of the body that might come in direct contact with the infant’s skin or where the drug might be ingested by the infant via licking.

Toxicity

Patients who have aspirin toxicity can have a myriad of symptoms. Symptoms of mild toxicity can be but are not limited to tinnitus, dizziness, lethargy, nausea, and vomiting. For more severe toxicity the signs and symptoms include hyperthermia, tachypnea leading to respiratory alkalosis, high anion gap metabolic acidosis, hypokalemia, hypoglycemia, seizures, coma, and cerebral edema. Death commonly occurs due to cardiopulmonary edema secondary to pulmonary edema.[rx][rx][rx]