NON OPIOID ANALGESICS and ANTI-INFLAMMATORY MEDICATIONS

Paracetamol has analgesic and antipyretic e ects that are similar to aspirin, but little or no antiin ammatory activity. It is generally accepted that it has little e ect on extracerebral COX-1 or COX-2, although it inhibits central COX-3. Consequently, it prevents the enhanced synthesis of prostaglandin E2 in the hypothalamus during pyrexia, and thus reduces elevated body temperature. It has similar e ects to aspirin on non-speci c pain. Paracetamol is also synergistic with opioid medications, reducing the overall opioid requirement by 20-30%. At normal therapeutic dosages, primarily hepatic metabolism to sulfate and glucuronide conjugates, while a small amount is metabolized by CYP2E1 to a highly reactive intermediate, N-acetyl-p-benzoquinoneimine (NAPQI), which is conjugated rapidly with glutathione and inactivated to nontoxic cysteine and mercapturic acid conjugates. At toxic doses (as little as 4 g daily) glutathione conjugation becomes insu cient to meet the metabolic demand causing an increase in NAPQI concentrations, which may cause hepatic cell necrosis.