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).
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.
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.
Aspirin allows for pain relief through its ability to decrease inflammation. It also may inhibit pain stimuli in the central nervous system.
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.
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.
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
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
Chheng Tang, Pharm. D. Candidate, Temple University, August 2002
A. Muller, S. Sheen
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