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NAPQI
NAPQI, also known as NAPBQI or ''N''-acetyl-''p''-benzoquinone imine, is a toxic byproduct produced during the xenobiotic metabolism of the analgesic paracetamol (acetaminophen). It is normally produced only in small amounts, and then almost immediately detoxified in the liver. However, under some conditions in which NAPQI is not effectively detoxified (usually in the case of paracetamol overdose), it causes severe damage to the liver. This becomes apparent 3–4 days after ingestion and may result in death from fulminant liver failure several days after the overdose. Metabolism In adults, the primary metabolic pathway for paracetamol is glucuronidation. This yields a relatively non-toxic metabolite, which is excreted into bile and passed out of the body. A small amount of the drug is metabolized via the cytochrome P-450 pathway (to be specific, CYP3A4 and CYP2E1) into NAPQI, which is extremely toxic to liver tissue, as well as being a strong biochemical oxidizer. In an avera ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Paracetamol Overdose
Paracetamol poisoning, also known as acetaminophen poisoning, is caused by excessive use of the medication paracetamol (acetaminophen). Most people have few or non-specific symptoms in the first 24 hours following overdose. These include feeling tired, abdominal pain, or nausea. This is typically followed by a couple of days without any symptoms, after which yellowish skin, blood clotting problems, and confusion occurs as a result of liver failure. Additional complications may include kidney failure, pancreatitis, low blood sugar, and lactic acidosis. If death does not occur, people tend to recover fully over a couple of weeks. Without treatment, death from toxicity occurs 4 to 18 days later. Paracetamol poisoning can occur accidentally or as an attempt to die by suicide. Risk factors for toxicity include alcoholism, malnutrition, and the taking of certain other hepatotoxic medications. Liver damage results not from paracetamol itself, but from one of its metabolites ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Paracetamol
Paracetamol, also known as acetaminophen, is a medication used to treat fever and mild to moderate pain. Common brand names include Tylenol and Panadol. At a standard dose, paracetamol only slightly decreases body temperature; it is inferior to ibuprofen in that respect, and the benefits of its use for fever are unclear. Paracetamol may relieve pain in acute mild migraine but only slightly in episodic tension headache. However, the aspirin/paracetamol/caffeine combination helps with both conditions where the pain is mild and is recommended as a first-line treatment for them. Paracetamol is effective for post-surgical pain, but it is inferior to ibuprofen. The paracetamol/ibuprofen combination provides further increase in potency and is superior to either drug alone. The pain relief paracetamol provides in osteoarthritis is small and clinically insignificant. The evidence in its favor for the use in low back pain, cancer pain, and neuropathic pain is insufficient. In the sho ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Acetaminophen Metabolism
Paracetamol, also known as acetaminophen, is a medication used to treat fever and mild to moderate pain. Common brand names include Tylenol and Panadol. At a standard dose, paracetamol only slightly decreases body temperature; it is inferior to ibuprofen in that respect, and the benefits of its use for fever are unclear. Paracetamol may relieve pain in acute mild migraine but only slightly in episodic tension headache. However, the aspirin/paracetamol/caffeine combination helps with both conditions where the pain is mild and is recommended as a first-line treatment for them. Paracetamol is effective for post-surgical pain, but it is inferior to ibuprofen. The paracetamol/ibuprofen combination provides further increase in potency and is superior to either drug alone. The pain relief paracetamol provides in osteoarthritis is small and clinically insignificant. The evidence in its favor for the use in low back pain, cancer pain, and neuropathic pain is insufficient. In the ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Glutathione
Glutathione (GSH, ) is an antioxidant in plants, animals, fungi, and some bacteria and archaea. Glutathione is capable of preventing damage to important cellular components caused by sources such as reactive oxygen species, free radicals, peroxides, lipid peroxides, and heavy metals. It is a tripeptide with a gamma peptide linkage between the carboxyl group of the glutamate side chain and cysteine. The carboxyl group of the cysteine residue is attached by normal peptide linkage to glycine. Biosynthesis and occurrence Glutathione biosynthesis involves two adenosine triphosphate-dependent steps: *First, γ-glutamylcysteine is synthesized from L- glutamate and cysteine. This conversion requires the enzyme glutamate–cysteine ligase (GCL, glutamate cysteine synthase). This reaction is the rate-limiting step in glutathione synthesis. *Second, glycine is added to the C-terminal of γ-glutamylcysteine. This condensation is catalyzed by glutathione synthetase. While all animal ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Acetylcysteine
Acetylcysteine, also known as ''N''-acetylcysteine (NAC), is a medication that is used to treat paracetamol overdose and to loosen thick mucus in individuals with chronic bronchopulmonary disorders like pneumonia and bronchitis. It has been used to treat lactobezoar in infants. It can be taken intravenously, by mouth, or inhaled as a mist. Some people use it as a dietary supplement. Common side effects include nausea and vomiting when taken by mouth. The skin may occasionally become red and itchy with any route of administration. A non-immune type of anaphylaxis may also occur. It appears to be safe in pregnancy. For paracetamol overdose, it works by increasing the level of glutathione, an antioxidant that can neutralise the toxic breakdown products of paracetamol. When inhaled, it acts as a mucolytic by decreasing the thickness of mucus. Acetylcysteine was initially patented in 1960 and came into medical use in 1968. It is on the World Health Organization's List of Essentia ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Hepatotoxins
Hepatotoxicity (from ''hepatic toxicity'') implies chemical-driven liver damage. Drug-induced liver injury is a cause of acute and chronic liver disease caused specifically by medications and the most common reason for a drug to be withdrawn from the market after approval. The liver plays a central role in transforming and clearing chemicals and is susceptible to the toxicity from these agents. Certain medicinal agents, when taken in overdoses (e.g. paracetamol) and sometimes even when introduced within therapeutic ranges (e.g. halothane), may injure the organ. Other chemical agents, such as those used in laboratories and industries, natural chemicals (e.g., microcystins), and herbal remedies (two prominent examples being kava, mechanism unknown, and comfrey, through its pyrrolizidine alkaloid content) can also induce hepatotoxicity. Chemicals that cause liver injury are called hepatotoxins. More than 900 drugs have been implicated in causing liver injury (see LiverTox, externa ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Centrilobular Necrosis
Centrilobular necrosis refers to the necrosis of the centrilobular tissue of the hepatic lobule. The centrilobular zone of the lobule is most prone to metabolic toxins such as those generated in alcoholic hepatitis. In acetaminophen overdose, glutathione depletion occurs and the highly reactive NAPQI NAPQI, also known as NAPBQI or ''N''-acetyl-''p''-benzoquinone imine, is a toxic byproduct produced during the xenobiotic metabolism of the analgesic paracetamol (acetaminophen). It is normally produced only in small amounts, and then almost imme ... will bind to the liver cells causing centrilobular necrosis. References Necrosis {{disease-stub ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
CYP2E1
Cytochrome P450 2E1 (abbreviated CYP2E1, ) is a member of the cytochrome P450 mixed-function oxidase system, which is involved in the metabolism of xenobiotics in the body. This class of enzymes is divided up into a number of subcategories, including CYP1, CYP2, and CYP3, which as a group are largely responsible for the breakdown of foreign compounds in mammals. While CYP2E1 itself carries out a relatively low number of these reactions (~4% of known P450-mediated drug oxidations), it and related enzymes CYP1A2 and CYP3A4 are responsible for the breakdown of many toxic environmental chemicals and carcinogens that enter the body, in addition to basic metabolic reactions such as fatty acid oxidations. Function CYP2E1 is a membrane protein expressed in high levels in the liver, where it composes nearly 50% of the total hepatic cytochrome P450 mRNA and 7% of the hepatic cytochrome P450 protein. The liver is therefore where most drugs undergo deactivation by CYP2E1, either directly o ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Chemical Pathology
Clinical chemistry (also known as chemical pathology, clinical biochemistry or medical biochemistry) is the area of chemistry that is generally concerned with analysis of bodily fluids for diagnostic and therapeutic purposes. It is an applied form of biochemistry (not to be confused with medicinal chemistry, which involves basic research for drug development). The discipline originated in the late 19th century with the use of simple chemical reaction tests for various components of blood and urine. In the many decades since, other techniques have been applied as science and technology have advanced, including the use and measurement of enzyme activities, spectrophotometry, electrophoresis, and immunoassay. There are now many blood tests and clinical urine tests with extensive diagnostic capabilities. Most current laboratories are now highly automated to accommodate the high workload typical of a hospital laboratory. Tests performed are closely monitored and quality controlled ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Human Drug Metabolites
Humans (''Homo sapiens'') are the most abundant and widespread species of primate, characterized by bipedalism and exceptional cognitive skills due to a large and complex brain. This has enabled the development of advanced tools, culture, and language. Humans are highly social and tend to live in complex social structures composed of many cooperating and competing groups, from families and kinship networks to political states. Social interactions between humans have established a wide variety of values, social norms, and rituals, which bolster human society. Its intelligence and its desire to understand and influence the environment and to explain and manipulate phenomena have motivated humanity's development of science, philosophy, mythology, religion, and other fields of study. Although some scientists equate the term ''humans'' with all members of the genus ''Homo'', in common usage, it generally refers to ''Homo sapiens'', the only extant member. Anatomically mode ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Cytochrome P450 Oxidase
Cytochromes P450 (CYPs) are a superfamily of enzymes containing heme as a cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are important for the clearance of various compounds, as well as for hormone synthesis and breakdown. In 1963, Estabrook, Cooper, and Rosenthal described the role of CYP as a catalyst in steroid hormone synthesis and drug metabolism. In plants, these proteins are important for the biosynthesis of defensive compounds, fatty acids, and hormones. CYP enzymes have been identified in all kingdoms of life: animals, plants, fungi, protists, bacteria, and archaea, as well as in viruses. However, they are not omnipresent; for example, they have not been found in ''Escherichia coli''. , more than 300,000 distinct CYP proteins are known. CYPs are, in general, the terminal oxidase enzymes in electron transfer chains, broadly categorized as P450-containing systems. The term "P450" is derived fro ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
