Advantages And Disadvantages Of Acetaminophene

The United States is currently in the midst of an Opioid overdose epidemic. Deaths from overdoses of prescription drugs continue to be the leading cause of unintentional death for Americans. Last year, 47,055 people died from drug overdoses - 1.5 times greater than the number killed in car crashes. Overdose is an excessive and very dangerous dose of a drug. Opioids are substances that act on opioid receptors to produce morphine-like effects. Medically, they are primarily used for pain relief. The most commonly prescribed opioid medications are Vicodin, OxyContin, and Percocet. Drug overdoses can be either accidental or intentional. They occur when a person takes more than the medically recommended dose. Treatments for overdose include medications

In the United States, 40 people die across each day due to overdosing on narcotic prescription medicine. One of the most commonly abused prescriptions is opioids painkillers such as Vicodin and codeine. Another medicine to treat anxiety and sleep aids such as Valiums and Xanax. Other abused prescriptions are stimulants to treat Attention Deficit Hyper Disorder (ADHD) like Adderall and Ritalin. When the overdose first became a problem, 60 percent of NC prescription overdose victims were dying before the arrival of emergency medical

It is used to treat chronic or acute pain. It works by inhibiting the chemical messengers called the prostaglandins. Prostaglandins help transmit pain signals, induce fever and promote inflammation of swelling of tissues, normally happens after an injury or illness. Acetaminophen helps by blocking the signals of pain to the body. Unlike NSAIDs it does not have an anti- inflammatory action. Acetaminophen is rapidly absorbed in the stomach and the small intestines. The therapeutic dose is 500mg every 4-6 hours. A single dose over one hundred and fifty mg/kg are considered toxic. Although most times it also depends on how often you take the medication and how often you accidently overdose. The statistic gives you some good idea of what we should be worried about. Acetaminophen toxicity can occur at any age. Most common in patients with chronic alcohol abuse or malnutrition. Children because of the incorrect weight and dosage given. Older teenager or adult patients will occur with intent to harm themselves. When it is ingested into the body, a normal dose is easily broken down through the liver enzymes and excreted through urine. However in large amounts it overwhelms the liver and it cannot be broken down as easy, thus killing the liver tissue. It is the most common cause of hepatic failure in adults, usually requiring a liver

The U.S. Department of Health and Human Services (HHS) (2013) reported that U.S. prescription drugs, especially opioids analgesics, have been increasingly involved in drug overdose deaths. Unfortunately, drug overdose deaths from prescription drugs, especially opioids analgesics outnumbered deaths related to motor vehicle accidents back in 2009. Actually, in 2010 only, 16,651 deaths were connected to opioids overdose, an increase of 60 percent of overdose losses from any other drug class, prescribed or illegal. Specifically, in Florida, the attorney general of Florida (2012) stated that an average of seven Floridians die every day as a result of overdose from prescription drugs, which is five times greater than losses from the use of all illegal drugs put together.

People who regularly take too much acetaminophen are the largest group of people hospitalized for acute liver failure. And, on average, one person in the United States dies every year from H20 intoxication, or drinking too much water. And yet, no armies have formed against aspirin, Tylenol or water.

Xenobiotic metabolism is usually divided to phase I and II, where polar function groups are unmasked or introduced to the chemical structure (phase I or activation), followed by the conjugation between the xenobiotic and endogenous molecules, notably glucuronic acid, to further improve hydrophilicity (phase II or conjugation) (Golan 2012). Hepatic microsomal P450 are the enzymes that dominate the catalysis of phase I metabolism of xenobiotics (Table 1 and 2) (Anzenbacher and Anzenbacherova 2001). Therefore,

The pathogenesis behind the toxicity in Acetaminophen overdose is a result of chemical induced liver damage, hepatotoxicity. More specifically, this medication is metabolized in the liver, when there are large amounts of acetaminophen in the body the liver because depleted of it enzymes used to break down this medication. As a result the medication accumulates, causing hepatocellular necrosis

Acetaminophen, commonly known as Tylenol, is perhaps the most frequently used painkiller in the United States and Europe. Obtaining Tylenol is as simple as driving to the local grocery store. However, there is a hidden danger overlooked by citizens who frequently consume painkillers such as Tylenol: liver failure. “The active ingredient in Tylenol, acetaminophen, accounts for more than 100,000 calls to poison centers, roughly 60,000 emergency-room visits and hundreds of deaths each year in the United States. In England, it is the leading cause of liver failure requiring transplants” (Citation 1). The outrageous number of medical complications Tylenol is causing is due to how readily available the drug is and how people are taking more than the recommended dose regularly. Liver damage can be reduced due to acetaminophen by making Tylenol prescription-only or by limiting the number of pills per package, thereby decreasing the availability of the pain-killer.

Thus, there is an urgency to evaluate the effects of immune response on APAP toxicity using a human KCs and hepatocyte co-culture system. Since a 3D multicellular system containing hepatocytes and other non-hepatocytes can better reflect the cell-cell interactions of a real situation [11], in this study, we used the 3D liver microtissues consisting of primary human hepatocytes (PHH) and KCs (1 : 1) to study the inflammation-mediated hepatotoxicity after acetaminophen overdose.

The AAP is a potential trigger of cytochrome P450 that induced the high reactive quinone-imine production. This matches with sulphahydryl groups in proteins and result in rapid depletion to intracellular glutathione(35). Generally, one parts of the potential intracellular antioxidant defensive system is glutathione that consumes the singlet oxygen, superoxide and hydroxyl radicals(36). Enhancing of intracellular flux of oxygen free radicals results from glutathione depletion leads to oxidative stress in hepatocytes(36). The increasing the serum levels of GOT, GPT and ALP have been attributed to the structural integrity hepatic damage(37). In liver tissue, GOT and GPT are located in cytosol and mitochondria. In following of liver damage, hepatocyte transport function disturbed

The majority of acetaminophen, approximately 90%, will be metabolized by glucuronidation (Lancaster et al., 2015). Approximately 10% will be metabolized by cytochrome p450 (Lancaster et al., 2015). From there it will become the reactive metabolite N-acetyl-p-benzo-quinone imine (NAPQI) (Lancaster et al., 2015). Under normal circumstances, glutathione (GSH) will convert NAPQI to a nontoxic metabolite (Lancaster et al., 2015). In cases where GSH depletion is present due to acetaminophen overdose, malnutrition, or alcoholism, NAPQI cannot be converted, leading to increased NAPQI levels and subsequently liver damage (Lancaster et al.,

Emerging evidence indicates that free radicals are involved in the pathogenesis of several digestive system disorders as well as in the regulation of biological processes such as aging. Previous reports have indicated that opioids induce apoptosis via stimulating an oxidative stress pathway that is associated with the production of superoxide and nitric oxide (NO) [11]. NO, together with reactive oxygen species (ROS), has a pivotal role in the regulation of apoptosis and necrosis in various cells. Hsiao et al. investigated the role of NO and ROS in the morphine-induced apoptosis. They found that the morphine treatment enhanced apoptosis through both NO and ROS pathways [12]. The inducible nitric oxide synthase (iNOS) enzyme is one of the most important enzymes involved in the generation of NO from the amino acid L-arginine.

Schematic representation of the contribution of LPS-induced inflammation to the increased APAP susceptibility. Transcriptome data obtained from this novel 3D co-culture model suggest that (A) In the absence of LPS, the widespread downregulation of mitochondrial respiratory chain related genes occurred in the cells treated with the high-dose of APAP. Altered expression of these genes could impair ETC-OXPHOS system and reduce the ATP synthesis which may induce the mitochondrial/cellular damage and the release of DAMPs. These DAMPs were recognized through TLR4 expressed on the KCs and triggered the KCs to secrete a small amount of pro-inflammatory cytokines such as IL-8. However, the high-dose APAP significantly repressed the expression of all

Intrinsic hepatotoxins predictably cause dose-dependent hepatocellular necrosis and their effects are reproducible. The period between onset and exposure is short, usually occurring within hours to days and the pattern of injury is fairly consistent in most people and animal models. Several drugs with intrinsic hepatotoxic potential are still widely used (eg, acetaminophen, iron sulfate and ethanol).

The most common mechanism of hepatotoxicity is related to oxidative stress and mitochondrial dysfunction. VPA induces oxidative stress via release of reactive oxygen species, fat peroxidation, mitochondrial membrane breakdown (Jafarian et al., 2013). The liver is one of the principle organs assaulted by reactive oxygen species (ROS), released by mitochondria, microsomes and