Description of Disease and Underlying theory
Acetaminophen, once ingested into the body is rapidly absorbed from the gastrointestinal tract into the blood stream where it reaches peak plasma concentration in as little as half an hour. Here, it circulates around the body for a period of up to 4 hours during which it produces its analgesic and antipyretic effects before the acetaminophen is metabolised and deactivated by the liver by a possible 3 pathways: Glucuronidation, sulfation and oxidation (Show below in Figure 2). The most commonly used pathway is the glucuronidation metabolism, closely followed by the sulfation pathway. These methods of metabolism deactivate the acetaminophen in the hepatocytes into non-toxic conjugated sulphate and glucuronide which are excreted in the urine [23] [24]. The majority of the initially ingested therapeutic dosage is metabolised this way, with the remaining acetaminophen being metabolised via the third hepatic cytochrome P45 oxidase pathway, primarily by the enzyme CYP2E1 [25]. When acetaminophen is metabolised via this method, a small amount of a highly reactive toxic intermediate
…show more content…
This is rapidly removed by the liver, by reacting with glutathione stored in the hepatocytes, conjugating the NAPQI into non-toxic cysteine and
o prepare Acetaminophen a water bath was set up in a 400-mL beaker and then placed onto a hotplate where it reached a boil. During the time it took for the water bath to boil, a 125-mL Erlenmeyer flask was obtained. P-aminophenol (1.5g) was weighed and then placed inside the Erlenmeyer flask. Deionized water (25 mL) was added to the flask followed by 35 drops of concentrated phosphoric acid. An additional 15 drops were added to the solution, since the initial 20 drops of concentrated phosphoric acid was not dissolving the p-aminophenol. Phosphoric acid was added to the reaction mixture because it acted as a catalyst for the reaction. The flask was then swirled gently until all of the p-aminophenol had dissolved. Once the water bath came to
The objective of this lab is to synthesize acetaminophen from p-aminophenol. The techniques used to do so, consist of: reflux with heat to allow reaction to occur at a reasonable time period, extraction and filtration to isolate the desired product, and characterization of the product by analyzing IR spectras and melting points. Acetaminophen considered synthesized, primarily due to the IR spectrum exhibiting all the bond vibrations is the amide group. The percent yield of 124.6% imply that there was a mechanical error that occurred, thus, also tampering with the progression of the chemical reaction. The wide melting point range of 165 C-169 C denote the impurity of the acetaminophen product.
The periodic table has 118 elements. The compound we are going to focus on is acetaminophen. What is the drug acetaminophen? It is an over-the-counter drug that serves as a painkiller and a fever reducer. It is used to treat various conditions such as muscle aches, backache, toothaches, headaches, and arthritis. Although it is considered an analgesic because it is a pain reliever, it has no anti-inflammatory properties. Also, because it contains no anti-inflammatory properties, it is not a member of the non-steroidal anti-inflammatory drugs, also known as NSAIDs.
aspect to assess the safety and appropriateness of IV acetaminophen use in hospital setting. Several published hospital utilization medication reports showed an increase consumption of intravenous acetaminophen.
What started off as a sedative drug Ketamine walked out of a clinic and on to the streets as a recreational drug known as “Special K”.
Acetaminophen also known as paracetamol and APAP, is a prescription and over-the-counter drug that is used to treat moderate pain and reduce fever. It is also paired with other ingredients. For example, acetaminophen is mixed with guaifenesin and phenylephrine to make the allergy medication Mucinex, acetaminophen is also used in over 600 other medications. When mixed with an opioid, such as, tramadol, it can be used to treat more severe pain. It is usually taken through the mouth but it can also be taken through injection and as a
Controls in these studies did not consume aspirin, but rather acetaminophen. In the juvenile rheumatoid arthritis study the three cases that were examined and compared developed persistent vomiting, noninflammatory encephalopathy, and showed an increase of serum salicylate level, which is linked to an increase of aspirin ingestion. Compared to the children receiving long-term aspirin therapy whom did not develop RS, these symptoms are strongly associated with RS. The animal experimental study results found that those with an arginine deficient diet and influenza infection and/or aspirin treatment had increased levels of SOCTase, SGOT levels, and liver lipids, and eventually went into a deep coma. Serum ammonia levels were also elevated among these groups. This study however does not correlate well with humans, as an arginine deficient diet would exceed the levels used within the ferrets. Lastly, in the Hospital for Children study previously mentioned, an association with RS and aspirin consumption was found, however the next study found no statistically significant association between aspirin ingestion and
Acetaminophen(AMP), or N-acetyl-p-aminophenol (APAP), is one of the most frequently used medications in the United States. Its use alone or in combination preparations is widespread because of its analgesic and antipyretic properties and presumed safety in recommended doses. Acetaminophen is metabolized by hepatocytes. It is usually eliminated as a glucuronide or sulfate conjugate. Following overdose, however, the conjugation pathways become saturated, leading to accumulation of reactive intermediates such as N-acetyl-benzoquinoneimine, mercapturic acid, and probably others1.These reactions involve the cytochrome oxidase P-450 system, and the metabolites are normally detoxified by endogenous glutathione. When glutathione stores are depleted, hepatocyte necrosis ensues, typically with a centrilobular distribution. Liver necrosis can result from an acute overdose of a large amount of APAP, or from accumulation over several days. In case of our patient unintentional overdose due to the presumed safety of acetaminophen appeared to be the likely cause. Outcomes in cases of acetaminophen overdose are dependent upon several factors, including the amount of drug ingested and the time period between ingestion and initiation of drug-specific therapy. In cases of delayed treatment, death from irreversible liver failure due to the hepatotoxic effects of reactive acetaminophen intermediates may occur. Thrombocytopenia, as observed in our patient, is a well-reported clinical feature of acetaminophen toxicity and strongly correlates with the degree of hepatotoxicity, although it does not correlate with serum acetaminophen levels.2 Thus, the finding of thrombocytopenia early in the course of acetaminophen toxicity may help in identifying patients prone to severe hepatotoxicity. Acute renal failure, as observed in our patient, occurs in less than 2% of all acetaminophen poisonings and 10% of severely
The non-polar group (in yellow) enables salmeterol to dissolve in cell membranes and, thus, provides longer lasting effects than salbutamol when treating asthma. The CH2OH (circled in green) provides resistance to deactivation by enzymes which also contributes to longer action during the treatment of this condition.
Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist. It is thought that Ketamine helps to improve analgesia in those with pain refractory to high dose opiates as studied by Yang et al (1996) Mercadante et al (2009) explain that this could be due to a possible reversal of opioid tolerance. Normal doses can vary and Ketamine can be given in tablet form, as a subcutaneous “burst” or intravenously. The normal dose can range from 40-3200mg daily. Mercadante et al (2009) also outline that there may be a possibility that single dose ketamine may reduce hyperalgesia but more studies need to be done to confirm this.
In 1982, tragedy struck the Chicagoland area when several people died from taking Tylenol capsules laced with cyanide. Johnson & Johnson’s responsive recall of over 31 million bottles of Tylenol prompted a movement that made over-the-counter-medications in addition to millions of other consumer goods tamperproof. General Robert Wood Johnson’s credo— responsibility to the consumers, healthcare professionals, employees, community, then stakeholders, proved to be a moral compass for the organization (Markel, 2014).
As doses shift from low to high, the relative importance of individual enzymes involved in the metabolism may also shift. For example, at the high dose, oxon formation correlated best the CYP3A4 activity, while at the low dose, oxon formation correlated best with the higher affinity enzyme CYP2B6. Nutrition plays a role in metabolism(Croom, 2012). Poor nutrition limits the available energy for metabolism. Metabolizing enzymes require cofactors and micronutrients that may be lost with inadequate nutrition. Food itself can change the amount of xenobiotic available for metabolism by affecting its solubility, as well as by altering gastric emptying and bioavailability(Croom, 2012). Oral exposures involve first-pass metabolism, where the bulk of the blood collected from gastrointestinal tract first passes through the liver before being transported to the rest of the body(Croom, 2012). For xenobiotics with significant dermal absorption or significant exposure through inhalation, this can dramatically increase the amount available in the circulation and if the target organ is capable of bioactivation result in significant toxicity in that
The major portion of an oral dose of sucralose (85%) is unabsorbed and is excreted unchanged in the feces of rats, mice, rabbits, dogs and man.. Sucralose is absorbed from the upper part of the gastrointestinal tract by passive diffusion (Grice & Goldsmith ,2000) . Of the small amount of sucralose that is absorbed following consumption (approximately 15% of an oral intake), most is also excreted unchanged. About 2–3% of an oral intake undergoes common phase II metabolism, specifically, glucuronidation . Both unchanged sucralose and its glucuronide conjugates are excreted in urine, and readily eliminated with no bioaccumulation(Grotz & Munro
The main hypothesis of tolerance from regular use of salbutamol is associated with desensitisation of β2 adrenoceptor on the airway smooth muscle. [1][4][6] It is a protective mechanism to prevent overstimulation of receptors as a result of continuous salbutamol exposure. Desensitization consist of 2 main processes which are uncoupling of the receptors from adenylate cyclase and internalisation of uncoupled receptors. [1][4][6] Exposure
Caffeine is a naturally occurring stimulant found in coffee, tea, and chocolate, used as an additive in other energy drinks and acts as analgesic in some pain medications. (Reference) Metabolism of caffeine begins with the absorption of caffeine from consumption of a food or drink product that contains the stimulant, in the small intestine, to then be metabolized in the liver cell and distributed to different parts of the body. Caffeine is metabolized in the liver through an enzyme called cytochrome (CYP1A2). This enzyme controls most of the metabolism process of caffeine. Cytochrome is characterized by its wide range in activity, which is also a result of differences in our genetic makeup. The change in the DNA sequence has a significant