How common is acetaminophen poisoning?
9651517#0
Hydrocodone/paracetamol, also known as hydrocodone/acetaminophen, is the combination of the pain medications hydrocodone and paracetamol (acetaminophen). It is used to treat moderate to severe pain. It is taken by mouth. Recreational use is common in the United States.
Common side effects include dizziness, sleepiness, constipation, and vomiting. Serious side effects include addiction, respiratory depression (a decreased effort to breathe), low blood pressure, serotonin syndrome, severe allergic reactions, and liver failure. Use during pregnancy may harm the baby. Use with alcohol is not recommended. Hydrocodone works by binding to the mu-opioid receptor. How acetaminophen works is unclear.
Hydrocodone/paracetamol was approved for medical use in the United States in 1982. In the United States it is a schedule II controlled substance. In 2016 it was the 13th most prescribed medication in the United States with more than 43 million prescriptions. It is not available in the United Kingdom. It is sold under the trade name Vicodin among others.
Hydrocodone/paracetamol
19690848#0
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. This may 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 some cases will resolve while others will result in death.
Paracetamol poisoning can occur accidentally or as an attempt to end one's life. Risk factors for toxicity include alcoholism, malnutrition, and the taking of certain other medications. Liver damage results not from paracetamol itself, but from one of its metabolites, "N"-acetyl-"p"-benzoquinone imine (NAPQI). NAPQI decreases the liver's glutathione and directly damages cells in the liver. Diagnosis is based on the blood level of paracetamol at specific times after the medication was taken. These values are often plotted on the Rumack-Matthew nomogram to determine level of concern.
Treatment may include activated charcoal if the person presents soon after the overdose. Attempting to force the person to vomit is not recommended. If there is a potential for toxicity, the antidote acetylcysteine is recommended. The medication is generally given for at least 24 hours. Psychiatric care may be required following recovery. A liver transplant may be required if damage to the liver becomes severe. The need for transplant is often based on low blood pH, high blood lactate, poor blood clotting, or significant hepatic encephalopathy. With early treatment liver failure is rare. Death occurs in about 0.1% of cases.
Paracetamol poisoning was first described in the 1960s. Rates of poisoning vary significantly between regions of the world. In the United States more than 100,000 cases occur a year. In the United Kingdom it is the medication responsible for the greatest number of overdoses. Young children are most commonly affected. In the United States and the United Kingdom paracetamol is the most common cause of acute liver failure.
Paracetamol poisoning
2540987#49
Some common household chemicals are particularly dangerous to dogs:Poisoning with pain medications is common. Aspirin, paracetamol (acetaminophen, Tylenol), ibuprofen (Advil), and naproxen (Aleve) can all cause severe clinical signs in dogs, including vomiting blood, diarrhea, and abdominal pain. Specifically, aspirin can cause metabolic acidosis and bleeding disorders, acetaminophen can cause liver disease, ibuprofen can cause kidney disease, and naproxen can cause ulcers in the stomach, which can perforate. Treatment depends on the clinical signs.
Dog health
19690848#31
Many over-the-counter and prescription-only medications contain paracetamol. Because of its wide availability paired with comparably high toxicity, (compared to ibuprofen and aspirin) there is a much higher potential for overdose. Paracetamol toxicity is one of the most common causes of poisoning worldwide. In the United States, the United Kingdom, Australia, and New Zealand, paracetamol is the most common cause of drug overdoses. Additionally, in both the United States and the United Kingdom it is the most common cause of acute liver failure.
Paracetamol poisoning
19690848#32
In England and Wales an estimated 41,200 cases of paracetamol poisoning occurred in 1989 to 1990, with a mortality of 0.40%. It is estimated that 150 to 200 deaths and 15 to 20 liver transplants occur as a result of poisoning each year in England and Wales. Paracetamol overdose results in more calls to poison control centers in the US than overdose of any other pharmacological substance, accounting for more than 100,000 calls, as well as 56,000 emergency room visits, 2,600 hospitalizations, and 458 deaths due to acute liver failure per year. A study of cases of acute liver failure between November 2000 and October 2004 by the Centers for Disease Control and Prevention in the USA found that paracetamol was the cause of 41% of all cases in adults, and 25% of cases in children.
Paracetamol poisoning
10933090#89
On the same day, the American Society for the Prevention of Cruelty to Animals announces that "fears of widespread contamination of pet food with acetaminophen are unfounded," confirming the results of FDA investigators. The ASPCA collaborated with toxicologists with the California Animal Health and Food Safety System at the University of California, Davis. They found no acetaminophen contamination in three cans of the same food that tested positive for acetaminophen at a Texas laboratory. Additionally, since the cat that had eaten the food suffered kidney, but not liver, failure, acetaminophen poisoning seems unlikely.
Timeline of the 2007 pet food recalls
19283730#8
Acetaminophen (APAP) is a very common drug used to treat pain. High doses of acetaminophen has been shown to produce severe hepatotoxicity after being biotransformed to produce reactive intermediates. Acetaminophen is metabolized by CYP2E1 to produce NAPQI, which then causes significant oxidative stress due to increased reactive oxygen species (ROS). ROS can cause cellular damage in a multitude of ways, a few of which being DNA and mitochondrial damage and depletion of antioxidant enzymes such as glutathione. In terms of drug-drug interactions, acetaminophen activates CAR, a nuclear receptor involved in the production of metabolic enzymes, which increases the metabolism of other drugs. This could either cause reactive intermediates/drug activity to persist for longer than necessary, or the drug will be cleared quicker than normal and prevent any therapeutic actions from occurring. Ethanol induces CYP2E1 enzymes in the liver, which can lead to increased NAPQI formation in addition to that formed by acetaminophen.
Pharmacotoxicology
2919530#13
Many herbal and antioxidant remedies have been advocated for chronic liver disease but the evidence is not conclusive. Some support may be found in the orthodox medical use of two of these: N-acetyl cysteine (NAC), is the treatment of choice for acetaminophen overdose; both NAC and milk-thistle (Silybum marianum) or its derivative silibinin are used in liver poisoning from certain mushrooms, notably Amanita phalloides, although the use of milk-thistle is controversial. Some common herbs are known or suspected to be harmful to the liver, including black cohosh, ma huang, chaparral, comfrey, germander, greater celandine, kava, mistletoe, pennyroyal, skull cap and valerian.
Chronic liver disease
322197#12
Over-the-counter drugs, like acetaminophen, aspirin, or NSAIDs(ibuprofen, Naproxen, Ketoprofen), can be effective but tend to only be helpful as a treatment for a few times in a week at most. For those with gastrointestinal problems (ulcers and bleeding) acetaminophen is the better choice over aspirin, however both provide roughly equivalent pain relief. It is important to note that large daily doses of acetaminophen should be avoided as it may cause liver damage especially in those that consume 3 or more drinks/day and those with pre-existing liver disease. Ibuprofen, one of the NSAIDs listed above, is a common choice for pain relief but may also lead to gastrointestinal discomfort.
Tension headache
19690848#16
One strategy for reducing harm done by acetaminophen overdoses is selling paracetamol pre-combined in tablets either with an emetic or an antidote. Paradote was a tablet sold in the UK which combined 500 mg paracetamol with 100 mg methionine, an amino acid formerly used in the treatment of paracetamol overdose.
Paracetamol poisoning
102502#19
There is no known antidote for pennyroyal toxicity. Case studies involving pennyroyal poisonings have reported the use of gastric lavages and administration of emetics, or vomiting inducing agents, like activated charcoal. As glutathione depletion has been shown to regulate liver toxification, administration of N-acetylcysteine in similar doses as given for acetaminophen toxicity have been given to patients.
Mentha pulegium
1226250#13
Zone 1 (periportal) occurs in phosphorus poisoning or eclampsia.
Zone 2 (mid-zonal), although rare, is seen in yellow fever.
Zone 3 (centrilobular) occurs with ischemic injury, toxic effects, carbon tetrachloride exposure, or chloroform ingestion. In acute acetaminophen overdose, toxification occurs, mostly in Zone III which has the highest level of P450 micro-enzymes. That fact along with Zone III's decreased oxygen level helps to explain why it is preferentially one of the initial sites of damage.
Acute liver failure
19690848#2
The second phase occurs between 24 h and 72 h following overdose and consists of signs of increasing liver damage. In general, damage occurs in liver cells as they metabolize the paracetamol. The individual may experience right upper quadrant abdominal pain. The increasing liver damage also changes biochemical markers of liver function; International normalized ratio (INR) and the liver transaminases ALT and AST rise to abnormal levels. Acute kidney failure may also occur during this phase, typically caused by either hepatorenal syndrome or multiple organ dysfunction syndrome. In some cases, acute kidney failure may be the primary clinical manifestation of toxicity. In these cases, it has been suggested that the toxic metabolite is produced more in the kidneys than in the liver.
Paracetamol poisoning