Aspirin

Nonsteroidal anti-inflammatory drugs are a common class of analgesic typically used chronically for pain such as musculoskeletal pain including osteoarthritis. It is commonly used in the elderly population.

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

Non-steroidal anti-inflammatory drugs (NSAIDs) are the foundation of medical treatment for osteoarthritis (OA). It is the most common medication taken by an individual experiencing pain due to this degenerative joint disease. Not to mention, NSAIDS are prescribed for pain management in older adults since they are more efficacious than acetaminophen with the absence of central nervous system side effects of opioids

The production of aspirin begins salicylic acid which has been derived from the active site of salicin found in willow bark. This is done through multi-step process where substrates of salicin are converted into more basic products such as salicylic acid. Salicylic acid cannot be consumed by itself due to the fact that it is bitter and irritates the stomach causing side effects such as nausea and internal bleeding within the stomach. This is due to the fact that salicylic acid exists in protonated form in the stomach; therefore, the pH of the salicylic acid is low, thus affecting the lining of the stomach. Therefore, to stabilise salicylic acid, it is synthesized into acetylsalicylic acid also known as aspirin. Acetylsalicylic acid is not pronated in the stomach and thus, the pH of acetylsalicylic acid is not as low compared to salicylic acid, thus it does not affect the lining of the stomach as much compared to salicylic acid.

Aspirin may lead to adverse effects of bleeding, cardiac arrhythmia, edema, hypotension, tachycardia, agitation, cerebral edema, coma, confusion, dizziness, fatigue headache, hyperkalemia, rhabdomyalisis, hypersensitivity, and gi effects. According to the beers criteria, low dose aspirin should be based on risk vs benefit for those patients over 80 due to association with upper gastrointestinal events such as

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

In 1899, a German chemist named Felix Hoffmann, who worked for a Germany company called Bayer, rediscovered Gerhardt’s formula. Felix Hoffmann made some of the formula and gave it to his father who was suffering from the pain of arthritis. When he saw that there were good results he convinced Bayer to market the new drug to their company. Aspirin was first sold as a powder. According to Bayer's biography of Hoffman, it was 'mostly by chance' that the chemist Felix Hoffmann succeeded in mixing salicylic acid with acetic acid to create what is now widely recognized as something that mostly everyone knows and uses when in pain. It is a well-known medicine. Hoffmann didn’t like the alternative treatment, a juice from the willow tree bark that had been used for centuries as a painkiller and treatment for fever, but it had a lot of negative side effects, including nausea, gastro-intestine irritation,

However, when misused they can damage the body. More drugs in the last two years have been changed from prescription-only medication to over the counter medication than in the last decade (Blenkinsopp). The major reason for this is because most OTC medications contain acetaminophen, which is a pain and fever reducer. It is currently the most common medicine for pain relief in the United States (Greenlaw). The problem with acetaminophen is that it can severely damage your liver tissue and skin. It damages the Glutathione Pathway, which is necessary for detoxification. This pathway is strongest antioxidant protector in the liver. Acetaminophen breaks down this pathway and in turn decreases the protection from toxins over time. It also accounts for about 460 deaths, 56,000 emergency room visits, and 2,6000 hospitalizations every year due to acute liver failure (University of Texas Medical Center). Acetaminophen in the correct amount can be advantageous, but one must understand the recommended proper dosage and frequency that the medication should be

Just a few weeks ago, it has come to my attention through a study conducted at Copenhagen University Hospital Gentofte led by Cardiology Professor, Gunnar Gislason. Through the study, it has been discovered that common painkillers, such as ibuprofen (Motrin), gives the person an increased risk of cardiac arrest by 31%. It was found that Non-Steroidal Anti-Inflammatory drugs (NSAIDs) have been linked with it as well and the most common is ibuprofen. Gislason says to only take ibuprofen when it is absolutely necessary, be cautious when using it, and to never take more than 1,200 mg a day. Previous studies have shown that NSAIDs are related to the cardiovascular risk. “Naproxen is probably the safest NSAID, and we take up to

Experiments showed that the main route of drug elimination is different in various species, renal excretion being the most important in man and rhesus monkey and biliary excretion the most important in rat and dog. The lack of enterohepatic recycling in man probably accounts for the reduced gastrointestinal toxicity of this drug (Menasse et al., 1978). Earlier workers documented enhanced rates of leucopoiesis and depressed erythropoiesis in bone marrow on aspirin treatment (Merchant and Modi, 2004). NSAIDs are eicosanoid depressing drugs which are used to treat osteoarthritis, rheumatoid arthritis, muscular ache by suppressing pain and inflammation. NSAIDs have been reported to diminish bone formation, healing, and remodeling (Nair et al., 2006). The hazard of diclofenac at doses C150 mg daily is estimated to be comparable to that of rofecoxib and celecoxib, as well as ibuprofen administered at high doses (McGettigan and Henry, 2011). Altered homeostasis has been reported by the use of diclofenac and its major effects are found in platelets functions (Power et al.,

According to Nordqvist,Medicalnewstoday,(2015); Aspirin is a still till this day a very well known and popularly used medication in the world. As an over the counter or (OTC) product since 1915. Aspirin was discovered in 1763 by Edward Stone, he had been documenting his symptoms his been having such as fever, pain, chills, and fatigue when he had discovered Salicylic Acid which is the main reactant in Aspirin. As the years passed many other Salicylate Medicines have been discovered such as Salicin and Sodium Salicylic acids. Many forms of aspirin were created such as capsules and chewable gummies.

It is considered to be complex with peripheral COX inhibition and central effects. The mechanism of peripheral COX inhibition by paracetamol is different from NSAIDs. NSAIDs inhibit COX by competing with AA for the active site of the enzyme, whereas paracetamol reduces the ferryl protoporphyrin IX radical cation, on the POX site, that generates the tyrosine-385 radical at COX site, which is essential for the conversion of AA to PGH2 (Anderson 2008; 1, Jóźwiak-Bebenista & Nowak 2014)13. The effect of paracetamol can be reduced in the presence of hydroperoxide-generating lipoxygenase enzymes within the cell (peroxide tone) or by swapping the POX with substrate as Prostaglandin G2(Anderson 2008; 1, Jóźwiak-Bebenista & Nowak 2014)13 . T(Figure 2). This peroxide tone and swapping might explain why paracetamol has a different side effect profile to NSAIDs.. Centrally paracetamol acts by inhibiting COX, interacting with endogenous opioids pathways, activating the serotonergic descending neuronal pathway, inhibiting the nitric oxide pathway (neurotransmittor in the nociceptive processes in the spinal cord) and interacting with the cannabinoid

NSAIDS inhibits COX-1 and COX-2 which damages the gastrointestinal tract. However, NSAIDs with selective COX-2 inhibition was much safer for patients with ulcerative colitis as these drugs presented much lower risk of UC relapse. Studies showed COX-2 selective NSAIDs, Celecoxib and Etoricoxib, were not associated with relapse of this disease compared to placebo (2). Patients with diagnosis of UC may also use acetaminophen and aspirin for pain control as no association was found between the two medications and incidence of ulcerative colitis

NSAIDs work commonly by blocking the action of cyclooxygenase isoenzymes (COX-1, COX-2). This consequently blocks the production of prostaglandins which are responsible for inflammation9. The COX-2 isoenzyme is the particular enzyme that produces prostaglandins, which cause inflammation. On the other hand, COX-1 isoenzymes do not produce these inflammatory prostaglandins, but have various other effects. An important effect is maintaining a healthy stomach and intestinal lining9. Traditional non-selective NSAIDs block the action of both COX-1 and COX-2. These can lead to harmful side effects such as intestinal damage and peptic ulcers, amongst others. NSAIDs are commonly prescribed with a PPI to counteract these harmful side effects. In comparison to the other NSAIDs, Etoricoxib is an orally active, selective COX-2 inhibitor2. It does not inhibit the cyclooxygenase-1 isoenzyme. Therefore it simply lowers the prostaglandin production, consequently meaning that there are fewer chances of stomach-related side effects9.

A historical Development that relates to Aspirin is the father of our modern Medicine Hippocrates, who was a Greek Physician, left records of how they treated headaches, fevers and pains, and to ease child- bearing pains with a powder made of the leaves and bark form a Willow Tree. Also the Ancient Egyptians left a medical text called “Ebers Papyrus” which is also lists willow among a list a plant and animal remedies for pain relief, fever reduction, and as an anti-inflammatory. Also the Roman Celsus recommended Willow extract for treating the symptoms of Inflammations, swollen, red, feverish area, and pain. (Wikipedia “history”) This is relatable as the bark and leaves of the Willow tree are a natural resource of the Salicylic acid, which is found in Aspirin, which made the patients feel better while healing them, similar to the modern Aspirin. Further along in Human history we know that Edward Stone discovered and isolated the key chemical in the Willow bark/leaves called Salicylic Acid. The problem with the Salicylic acid was that it was extremely tough on stomachs and could cause nausea and vomiting, hence the next step in developing Aspirin was to find an effective buffer that would make the Salicylic acid easier for the stomach to handle, a French chemist named Charles Frederic Gerhardt was one of the first to attempt at creating a suitable buffer for Salicylic acid was to combine it with Sodium and Acetyl Chloride,