Description<\/h3>\n\n\n\n
Paracetamol (also called acetaminophen) is a widely used analgesic and antipyretic agent.\n<\/p>\n\n\n\n
Paracetamol is well absorbed<\/a> in the gastrointestinal tract. Oral bioavailability<\/a> is dose dependant: with larger doses, the hepatic first pass effect<\/a>\n is reduced due to overwhelming of the liver enzymatic capacity; and \ntherefore, bioavailability is increased. Rectal administration of \nparacetamol is also feasible. In this case, bioavailability is \ninconsistent and in overall reduced, due to incomplete dissolution of \nthe suppository in the rectum. The absorption rate<\/a> through this route of administration is elongated.\n<\/p>\n\n\n\n Paracetamol is distributed<\/a>\n throughout the body fluids in a homogeneous way. The analgesic activity\n is attributable to the small fraction that penetrates into the brain. \nParacetamol given at therapeutic doses binds to plasma proteins<\/a> at less than 20%. In case of intoxication, this proportion may increase to up to 50%.\n<\/p>\n\n\n\n Paracetamol is essentially metabolized<\/a>\n in the liver by conjugation with glucuronic acid (55%) and sulfuric \nacid (35%). Hepatotoxic metabolites are produced in small amounts by the\n cytochrome P450 (isoenzyme CYP2E1). In the therapeutic plasma \nconcentration range, this metabolite is detoxified by conjugation with \nglutathione. In case of intoxication the amount of this toxic metabolite\n increases and outweighs the amount of available glutathion, which can \nlead to hepatic failure and renal tubular necrosis.\n<\/p>\n\n\n\n Metabolites are excreted<\/a>\n through the kidneys in the urine. Only 2-5% of the dose is excreted in \nan unchanged form in the urine. As a consequence of its short \nelimination half-life<\/a> (1-3h), 24 hours after the ingestion of a single dose of paracetamol, 98% of the dose is eliminated.<\/p>\n\n\n\n Since paracetamol is mostly eliminated by hepatic metabolism<\/a>, patients with severe hepatic failure have a considerably longer elimination half-life<\/a>, and therefore, paracetamol must be used cautiously in such patients.\n<\/p>\n\n\n\n Intoxication are not infrequent because paracetamol \nis one of the most widely used over-the-counter drugs. Paracetamol \nintoxication has important clinical implications as it can induce \nlife-threatening hepatic and renal failure. This failure is probably due\n to the accumulation of toxic metabolites, caused by an increase in \ntheir production and a decrease in their detoxification due to depletion\n of glutathione stores. The treatment of intoxication is:<\/p>\n\n\n\n Paracetamol pharmacokinetic parameters Oral bioavailability (F) 70%-90% Rectal bioavailability (F) 30%-70% Clearance (CL) 20 L\/h Volume of Distribution (Vd) 65 L Half-life (t1\/2) 2.5 h Description Paracetamol (also called acetaminophen) is a widely used analgesic and antipyretic agent. Paracetamol is well absorbed in the gastrointestinal tract. Oral bioavailability is dose dependant: with larger doses, the … <\/p>\nClinical implications<\/h3>\n\n\n\n
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