Instruct: Given a question, retrieve passages that can help answer the question.
Query: Can you die from acetaminophen poisoning?
The Chicago Tylenol murders were a series of poisoning deaths resulting from drug tampering in the Chicago metropolitan area in 1982. The victims had all taken Tylenol-branded acetaminophen capsules that had been laced with potassium cyanide. A total of seven people died in the original poisonings, with several more deaths in subsequent copycat crimes.
Pesticide use is widespread in Latin America, as around US $3 billion are spend each year in the region. It has been recorded that pesticide poisonings have been increasing each year for the past two decades. It was estimated that 50–80% of the cases are unreported. It is indicated by studies that organophosphate and carbamate insecticides are the most frequent source of pesticide poisoning.
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.
In 1999, the EPA banned most uses of methyl parathion and azinphos methyl, citing the risks they pose to children. Both methyl parathion and azinphos methyl are organophosphates. Organophosphates are pesticides that kill insects by disrupting nerve impulses. Unfortunately, these pesticides have the same effect on humans. In 2000, the EPA banned another organophosphate, (chlorpyrifos), that was common in the agriculture industry, household cleaners and commercial pest control products, due to a study showing that chlorpyrifos caused weakness, vomiting and diarrhea in baby rats.
Corticosteroids (cortisone), accutane (isotretinoin) and other vitamin A derivatives, barbiturates, certain antibiotics, propofol, volatile anesthetics, non-depolarizing muscle relaxants, some local anesthetics, statins, fibrates, glitazones, beta blockers, biguanides, amiodarone, some chemotherapies, some neuroleptics, nucleoside reverse transcriptase inhibitors and various other drugs.
Organophosphate is the general name for esters of phosphoric acid and is one of the organophosphorus compounds. They can be found as part of insecticides, herbicides, and nerve gases, amongst others. Some less-toxic organophosphates can be used as solvents, plasticizers, and EP additives. The use of organophosphates accounts for approximately 38% of all pesticide use globally.
The word "organophosphates", when appearing in communications (e.g., from the press or the government), in areas such as agriculture, the environment, and human and animal health, very often refers to a group of insecticides (pesticides) that act on the enzyme acetylcholinesterase (see also carbamates). Today, organophosphates make up about 50% of the killing agents in chemical pesticides.
The toxin has been implicated in cases of respiratory irritation, inflammation of the eye and severe contact dermatitis in fishermen. Antillatoxin is a very potent neurotoxin, although exact toxicity differs between species. The lethal concentration LC is about 0.1 µM for goldfish, making it the most potent toxin known for goldfish after brevetoxin. It can be cytotoxic to single cerebellar granule cells at concentrations as low as 20 nM in rats but more typically at 50 nM.
As an alternative to taking prescription drugs, some evidence shows that an average person seeking short-term help may find relief by taking over-the-counter antihistamines such as diphenhydramine or doxylamine. Diphenhydramine and doxylamine are widely used in nonprescription sleep aids. They are the most effective over-the-counter sedatives currently available, at least in much of Europe, Canada, Australia, and the United States, and are more sedating than some prescription hypnotics. Antihistamine effectiveness for sleep may decrease over time, and anticholinergic side-effects (such as dry mouth) may also be a drawback with these particular drugs. While addiction does not seem to be an issue with this class of drugs, they can induce dependence and rebound effects upon abrupt cessation of use. However, people whose insomnia is caused by restless legs syndrome may have worsened symptoms with antihistamines.
On January 15, 2010, Johnson & Johnson announced a voluntary recall of several hundred batches of popular medicines, including Benadryl, Motrin, Rolaids, Simply Sleep, St. Joseph Aspirin and Tylenol. The recall was due to complaints of a musty smell suspected to be due to contamination of the packaging with the chemical 2,4,6-tribromoanisole. The full health effects of 2,4,6-tribromoanisole are not known but no serious events have been documented in medical literature. The recall came 20 months after McNeil first began receiving and investigating consumer complaints about moldy-smelling bottles of Tylenol Arthritis Relief caplets, according to the United States Food and Drug Administration (FDA). The recall included 53 million bottles of over-the-counter products including Tylenol, Motrin and Rolaids, Benadryl and St. Joseph's Aspirin, involving lots in the Americas, the United Arab Emirates and Fiji.
At very low doses, doxepin has not shown discontinuation or withdrawal effects nor rebound insomnia. Sustained effectiveness without apparent tolerance was demonstrated in clinical studies of up to 12 weeks duration. This appears to be in contrast to over-the-counter antihistamines like diphenhydramine and doxylamine and all other first-generation antihistamines, which are associated with rapid development of tolerance and dependence (by day 3 or 4 of continuous dosing) and loss of hypnotic effectiveness. It is for this reason that, unlike doxepin, they are not recommended for the chronic management of insomnia and are advised for only short-term treatment (i.e., 1 week). It is not entirely clear why doxepin and first-generation antihistamines are different in this regard, but it has been suggested that it may have to do with the lack of selectivity for the H receptor of the latter or may have to do with the use of optimal doses. Unlike very-low-dose doxepin, most first-generation antihistamines also have marked anticholinergic activity as well as associated side effects such as dry mouth, constipation, urinary retention, and confusion. This is particularly true in older people, and antihistamines with concomitant anticholinergic effects are not recommended in adults over the age of 65. Anticholinergic activity notably may interfere with the sleep-promoting effects of H receptor blockade.
In a concerted effort to reassure the public, Johnson & Johnson distributed warnings to hospitals and distributors and halted Tylenol production and advertising. On October 5, 1982, it issued a nationwide recall of Tylenol products; an estimated 31 million bottles were in circulation, with a retail value of over US $100 million ($267 million in 2018). The company also advertised in the national media for individuals not to consume any of its products that contained acetaminophen after it was determined that only these capsules had been tampered with. Johnson & Johnson offered to exchange all Tylenol capsules already purchased by the public for solid tablets.
H-antihistamines are among first-line therapy to treat gastrointestinal conditions including peptic ulcers and gastroesophageal reflux disease. Some formulations are available over the counter. Most side effects are due to cross-reactivity with unintended receptors. Cimetidine, for example, is notorious for antagonizing androgenic testosterone and DHT receptors at high doses.
As a result of the crisis, all Tylenol capsules were discontinued, as were capsules of other brand names. Retained by McNeil's president, Joseph Chiesa, new product consultant Martin Calle of management strategist Calle & Company conceived the world's first tamper-resistant gelatin-enrobed capsule called "Tylenol Gelcaps", which proved to resuscitate the 92% of capsule-segment sales lost to the recall. The tamper-resistant, triple-sealed safety containers were placed on the shelves of retailers 10 weeks after the withdrawal, and other manufacturers followed suit. The crisis cost the company more than $100 million, but Tylenol regained 100% of the market share it had before the crisis. The Tylenol murderer was never found, and a $100,000 reward offered by Johnson & Johnson remains unclaimed.
An organic diet is an effective way to reduce exposure to the organophosphorus pesticides commonly used in agricultural production. Organophosphate metabolite levels rapidly drop, and for some metabolites, become undetectable in children's urine when an organic diet is consumed. This is speculative based on a short study of 23 children, in which only a few organophosphate compounds were potentially reduced, no effect was shown for the majority of them that were found in the samples.
Astemizole (marketed under the brand name Hismanal, developmental code R43512) was a second-generation antihistamine drug that has a long duration of action. Astemizole was discovered by Janssen Pharmaceutica in 1977. It has been withdrawn from the market in most countries because of rare but potentially fatal side effects (QTc interval prolongation and related arrhythmias due to hERG channel blockade).
Currently most people who use an antihistamine to treat allergies use a second generation drug.
Bis-choline tetrathiomolybdate (or tiomolibdate USAN, trade name Decuprate), is a salt of tetrathiomolybdate (TTM, MoS) and choline currently under investigation as a therapy against Wilson's disease, a rare and potentially fatal disease in which the body cannot regulate copper. Wilson's disease is an autosomal recessive genetic disorder that is manifested by serious hepatic, neurologic or psychiatric symptoms. The disease is fatal if left undiagnosed and untreated. It is estimated that approximately 1 individual in every 30,000 worldwide have Wilson's disease, corresponding to approximately 15,000 individuals in the European Union and approximately 11,000 in the United States.
Compounds begin to break down as soon as they enter the body. The majority of small-molecule drug metabolism is carried out in the liver by redox enzymes, termed cytochrome P450 enzymes. As metabolism occurs, the initial (parent) compound is converted to new compounds called metabolites. When metabolites are pharmacologically inert, metabolism deactivates the administered dose of parent drug and this usually reduces the effects on the body. Metabolites may also be pharmacologically active, sometimes more so than the parent drug (see prodrug).
The brand was introduced in 1955 by McNeil Laboratories, a family owned pharmaceutical manufacturer. Two brothers took over the company from their father that year, and that year one of them learned about paracetamol, which was not on the US market at that time. To avoid competing with aspirin, they marketed it as a product to reduce fever in children, packaging it like a red fire truck with the slogan, "for little hotheads". The name "Tylenol" and the generic name "acetaminophen" were generated by McNeil from the chemical name of the drug. Johnson & Johnson bought McNeil in 1959, and one year later the drug was made available over the counter.
The level of regulation includes Schedule IV Non-Narcotic (depressant) (ACSCN 2285) in the United States under the Controlled Substances Act 1970—but along with a few other barbiturates and at least one benzodiazepine, and codeine, dionine, or dihydrocodeine at low concentrations, it also has exempt prescription and had at least one exempt OTC combination drug now more tightly regulated for its ephedrine content. The phenobarbitone/phenobarbital exists in subtherapeutic doses which add up to an effective dose to counter the overstimulation and possible seizures from a deliberate overdose in ephedrine tablets for asthma, which are now regulated at the federal and state level as: a restricted OTC medicine and/or watched precursor, uncontrolled but watched/restricted prescription drug & watched precursor, a Schedule II, III, IV, or V prescription-only controlled substance & watched precursor, or a Schedule V (which also has possible regulations at the county/parish, town, city, or district as well aside from the fact that the pharmacist can also choose not to sell it, and photo ID and signing a register is required) exempt Non-Narcotic restricted/watched OTC medicine.
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.
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.
Acetaminophen (or paracetamol) is an analgesic medication that can affect the liver when administered in high doses. Acetaminophen is predominantly conjugated into glucuronate and sulfate moieties by Phase II metabolism. A small percentage is metabolized by the cytochrome P450 pathway to a toxic metabolite, NAPQI. NAPQI is conjugated by glutathione to non-toxic cysteine and mercapturic acid moieties. In cases of acetaminophen toxicity, the Phase II conjugation enzymes are saturated, and a higher fraction is converted to NAPQI. The conjugation of NAPQI to glutathione occurs until glutathione is depleted from hepatic reserves, after which the toxic NAPQI accumulates and causes damage to the hepatocytes. This occurs primarily in areas of the liver that are relatively poorly perfused with oxygen, or furthest away from the hepatic artery, termed "Zone 3". Acetaminophen overdose is associated with Zone 3 necrosis, to the point that acute liver failure may result.
In closed environments, the concentration of carbon monoxide can easily rise to lethal levels. On average, 170 people in the United States die every year from carbon monoxide produced by non-automotive consumer products. However, according to the Florida Department of Health, "every year more than 500 Americans die from accidental exposure to carbon monoxide and thousands more across the U.S. require emergency medical care for non-fatal carbon monoxide poisoning" These products include malfunctioning fuel-burning appliances such as furnaces, ranges, water heaters, and gas and kerosene room heaters; engine-powered equipment such as portable generators; fireplaces; and charcoal that is burned in homes and other enclosed areas. The American Association of Poison Control Centers (AAPCC) reported 15,769 cases of carbon monoxide poisoning resulting in 39 deaths in 2007. In 2005, the CPSC reported 94 generator-related carbon monoxide poisoning deaths. Forty-seven of these deaths were known to have occurred during power outages due to severe weather, including Hurricane Katrina. Still others die from carbon monoxide produced by non-consumer products, such as cars left running in attached garages. The Centers for Disease Control and Prevention estimates that several thousand people go to hospital emergency rooms every year to be treated for carbon monoxide poisoning.