Acetominophen

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Acetaminophen is a popular an powerful analgesic worldwide but is not widely used everywhere in the world. (1) . Acetaminophen can also be used to reduce fever. It has analgesic and antipyretic effects that are very similar to that of aspirin but it lacks the anti-inflammatory effects. The following will explain the pharmacokinetics, pharmamcodynamics, and molecular toxicity of acetamenophen. Pharmacokinectics is the study of how a drug is processed in the body by examining absorption, distrbution, metabolism and excretion. Pharmacodynamics is the mechanism of the drug at physiological, biochemical and meolecular levels in the body. Recommended dosing For an adult the recommended oral dose is 325-1000mg, for a rectal dose it is 650mg, and the total daily dose should not exceed 4000mg.(1) For children, depending on their age and weight, the recommended dose is 40-480mg with no more than 5 doses being administered in one day. (2) Administration and absorption Acetaminophen can be administered orally, rectally, or intravenously. Orally acetaminophen is available in tablets/capsules (extended release and regular), chewable tablets, oral granules, and liquid suspensions. Rectally it is administered by suppositories and intravenously by IV. Absorption of acetaminophen is rapid and is almost completely absorbed by the gastrointestinal tract.(2) The 10-25% of the drug binds to the serum protein after a normal therapeutic dose. (2) The peak plasma concentration, which is the highest level of drug that can be obtained in the blood, is usually obtained within 30 minutes to 2 hours and may be slightly higher with suspensions. The half life in the plasma is 2 hours after a therapeutic dose. (2) The first pass effect (the loss of drug from metabolism by the liver) reduces the concentration by approximately 25% and about 85% of the dose is found in the urine with 24 hours of the oral administration. (2) Distribution Acetaminophen is uniformly distributed throughout most of the body’s fluids.(2) The drug should bind to plasma proteins, but it only does this at 20-50% during acute intoxication.(2) Metabolism At normal therapeutic doses approximately 85-90% of the compound is metabolized by the liver into sulfate and glucuronide metabolites, the remaining 10-15% undergoes oxidative metabolism which produces the heptotoxic metabolite. Clearance Adults and children will clear the drug differently. (1) In neonates and children ages three to nine primarily excrete acetaminophen as a sulfate conjugate, possibly because of a deficiency glucuronide formation in the children. (2) Formation of the acetaminophen glucuronide conjugate measured by high-performance liquid chromatography was quantified by the ratio of the area under the plasma concentration-time curve (AUC).

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