Why paracetamol is bad for liver?
The paracetamol(acetaminophen) is waidly used for fewer,headache,body pain…etc .Paracetamol was first made in 1877. It is the most commonly used medication for pain and fever in both the United States and Europe.It is on the World Health Organization’s List of Essential Medicines, the most effective and safe medicines needed in a health system. Paracetamol is available as a generic medication with trade names including Tylenol and Panadol, among others.The wholesale price in the developing world is less than US$ 0.01 per dose. In the United States, it costs about US$0.04 per dose.
Acute overdoses of paracetamol can cause potentially fatal liver damage. In 2011, the U.S. Food and Drug Administration launched a public-education program to help consumers avoid overdose, warning: “Acetaminophen can cause serious liver damage if more than directed is used.”In a 2011 Safety Warning, the FDA immediately required manufacturers to update labels of all prescription combination acetaminophen products to warn of the potential risk for severe liver injury and required that such combinations contain no more than 325 mg of acetaminophen Overdoses are frequently related to high-dose recreational use of prescription opioids, as these opioids are most often combined with acetaminophen The overdose risk may be heightened by frequent consumption of alcohol.
Paracetamol toxicity is the foremost cause of acute liver failure in the Western world, and accounts for most drug overdoses in the United States, the United Kingdom, Australia, and New Zealand. According to the FDA, in the United States, “56,000 emergency room visits, 26,000 hospitalizations, and 458 deaths per year [were] related to acetaminophen-associated overdoses during the 1990s. Within these estimates, unintentional acetaminophen overdose accounted for nearly 25% of the emergency department visits, 10% of the hospitalizations, and 25% of the deaths.”
Paracetamol is metabolised by the liver and is hepatotoxic; side effects are multiplied when combined with alcoholic drinks, and are very likely in chronic alcoholics or people with liver damage. Some studies have suggested the possibility of a moderately increased risk of upper gastrointestinal complications such as stomach bleeding when high doses are taken chronically. Kidney damage is seen in rare cases, most commonly in overdose.
Evolution of paracetamol in clinical care
Phenacetin and acetanilide, two aniline derivatives with analgesic and antipyretic properties, were first described by Harmon Morse in 1878 and Cahn & Hepp in 1886, respectively . Both were much later found to be prodrugs for the active compound N‐acetyl‐p‐aminophenol . The drug was given the approved name ‘paracetamol’ in 1957 and has been included in the published BritishPharmacopoeia since 1963 .
In the early 1970s the US Food and Drug Administration (FDA) outlined a safe adult dosage of up to 1000 mg every 4−6 h, not to exceed 4000 mg day−1, for no longer than 10 days. The recommendation was based primarily on animal toxicology data, one bioavailability study (n = 15 healthy adult males) and four Industry sponsored placebo‐controlled post‐partum analgesia trials that investigated single dose efficacy over 4−6 h in 338 women (n = 112 paracetamol 1000 mg; n = 113 paracetamol 650 mg; n = 113 placebo).
While most of the original data remains unpublished, the efficacy of this dosing regimen has subsequently been supported by clinical trials in a plethora of indications and extensive post‐marketing experience. Single dose trials and one large meta‐analysis inclusive of over 4000 patients have demonstrated that paracetamol dosed at 1000 mg provides superior analgesia compared with 650 mg , 500 mg and placebo but no less improvement than 2000 mg . Supra‐therapeutic doses of up to 8 g daily in healthy adults and 6 g daily in stroke patients have been shown to be relatively safe when used for up to 3 days , although one case of chronic use at 6 g daily for 14 years has been associated with the later development of cirrhosis . Long term safety data indicated no adverse clinical or biochemical effects in 1039 individuals taking paracetamol 1950−4000 mg daily for up to 1 year or 178 patients taking 2600 mg day−1 of paracetamol for 2 years in osteoarthritis trials .
Side effects with paracetamol when it is used appropriately both short and long term in a healthy adult are very rare. A review of eight observational studies has suggested a dose–response increase in all‐cause mortality, cardiovascular, renal and gastrointestinal adverse events for people taking therapeutic doses of paracetamol, although half of the studies did not adjust for concomitant NSAID use . In excess, paracetamol is known to have a broad toxic spectrum ranging from nausea and anorexia to severe liver damage and death as the sulphation pathway becomes acutely saturated and NAPQI is produced in excess. The sulphydryl donor N‐acetylcysteine (NAC), which serves as a precursor for glutathione and hence speeds the detoxification of NAPQI in this setting, is the only approved agent on the market for treatment of paracetamol overdose . Early diagnosis, modern medicine and use of NAC have considerably improved outcomes for patients who present early with toxicity.