Aspirin: The Basics
History
Willow bark was used before aspirin was synthesized in 1853, but aspirin was not used medicinally until 1899 when it was found to be effective for arthritis and well tolerated. “Aspirin” came from the German word for the compound, acetylspirsaure (which means plant’s acid).
Mechanism
Aspirin’s effect is largely due to its capacity to inhibit prostaglandin biosynthesis. It does this by irreversibly blocking the enzyme cyclooxygenase (COX), which catalyzes the conversion of arachidonic acid to endoperoxide compounds. At appropriate doses, the drug lessens the formation of both prostaglandin and thromboxane-A but not the leukotrienes. Aspirin is particularly effective because it irreversibly inactivates COX. Because the platelet lacks the machinery for synthesis of new protein, inhibition by aspirin persists until new platelets are formed (several days). There is no evidence that aspirin is a selective inhibitor of COX II. Most of an anti-inflammatory dose of aspirin is rapidly deacetylated to form salicylate as the active metabolite. Salicylate reversibly inhibits prostaglandin synthesis.
Anti-inflammatory effects
Aspirin interferes with chemical mediators of kallikrein system. This effect allows aspirin to inhibit granulocyte adherence to damaged vasculature, stabilize lysosomes and inhibit the migration of polymorphonuclear leukocytes and macrophages to the site of inflammation. It also reduces the synthesis prostaglandin and leukotriene mediators.
Analgesic effects
Aspirin allows for pain relief through its ability to decrease inflammation. It also may inhibit pain stimuli in the central nervous system.
Antipyretic effects
The fever associated with infection is thought to result from two actions. Aspirin blocks the pyrogen-induced production of prostaglandins, the central nervous system response to COX and the release of interleukin-1. These actions may reset the “temperature control” in the hypothalamus, thereby facilitating heat dissipation by vasodilatation.
Platelet effects
Single doses of aspirin (81 mg daily) produce a slight delay in hemostasis, which increases two-fold if administration is continued for a week. It is the irreversible blockade of platelet thromboxane synthesis that results in the inhibition of platelet aggregation.
Overdose
Serious adverse effects result when the amount ingested exceeds 50-175 mg/kg of body weight.1 Potentially lethal intoxications occur with ingestions exceeding 500 mg/kg.2 The infrequency of pure salicylate overdoses allows its complex nature to be underestimated.
Signs and symptoms of aspirin poisoning include tinnitus, headache, dizziness or vertigo, confusion, tachypnea, hyperpnea, metabolic acidosis, nausea, vomiting, dehydration/thirst and hypoglycemia.1
Specific poisoning issues
Treatment1
Decontamination: Orogastric lavage with saline followed by activated charcoal. Dialysis may be necessary to decrease mortality in severely poisoned patients.
Dehydration: I.V. fluids with KCl (Not D5W only)
Metabolic acidosis: Sodium Bicarbonate
Hyperthermia: Cooling blankets or sponge or both
Coagulopathy/hemorrhage: fresh frozen plasma, possibly vitamin K-phytonadione I.V.
Hypoglycemia: Dextrose 25g I.V. (with coma, seizures,or change in mental status)
Seizures: Diazepam 5-10mg I.V.
Hypokalemia: Potassium to maintain K+ 3.5 or higher
Clinical reviewers' comments
- Decontamination: be aware of gastric lavage’s limitations (i.e., will not clear bezoars, enteric coated tablets may lodge in the tube).
- Changes in mental status can be subtle (i.e., drowsiness), can indicate severe salicylate toxicity and the need for hemodialysis. Consult the poison control center for a toxicology consult if you have any doubts regarding the source of the patient’s change in mental status.
- It is critical to correct hypokalemia in order to successfully alkalinize the urine and enhance excretion of the aspirin.
- It is essential to remember that this is a multi-system poisoning.
- During the process of endotracheal intubation, the patient’s compensatory hyperventilation is lost. This is a critical period as the patient can become increasingly acidotic, increasing the CNS penetration of the aspirin, increasing the risk of seizures and death.
References
- Katzung, B.G. Basic and Clinical Pharmacology. 6th ed. Appleton and Lange; 1995:536-542.
- McEvoy, G.K., ed. AHFS Drug Information: Bethesda; 2001.
Author
Chheng Tang, Pharm. D. Candidate, Temple University, August 2002
Clinical reviewers at The Poison Control Center
A. Muller, S. Sheen