Paracetamol – Synthesis and Uses Discovered in 1877 by Harmon Northrop Morse at the John Hopkins University, Paracetamol was one of several aniline deriviatives that was found to have analgesic and antipyretic properties (Brodie 23). It was first synthesized by the reduction of p-nitrophenol with tin in glacial acetic acid; however was not used classified as a medication until ten year later (Bertolini 264). Initially, phenacetin, a closely related compound that exhibited similar physiological effects, became the popular over the counter drug for headaches (Bertolini 251). However, later research by Brodie and Axelrod in 1949 found that phenacetin was in fact metabolized into paracetamol within the body (Brodie and Axelrod 60). Subsequently, paracetamol quickly took the place of phenacetin and remains one of the most common over the counter medication for fever reduction and pain relief. Found in drugstores worldwide, paracetamol is commonly known by its American brand name, Tylenol. Paracetamol is chemically named N-acetyl – p – aminophenol. The chemical structure is an aromatic six-membered ring with a hydroxyl substituent placed para to the N-acetyl substituent. As the use of paracetamol increased, scientists and reserachers have looked into the most efficient methods of synthesizing the compound. In 1997, demand for paracetamol in the United States was estimated at 30-35 thousand tons per year(IARC 73). Global demand was similarly heavy in many other countries. There are numerous synthetic pathways that are presently known that seek to produce the compound most efficient manner. In determining efficiency, the many factors must be taken into account. The most important ones include the cost of the reagents,... ... middle of paper ... ...light of paracetmol’s physiological effects. The compound exhibits characteristics that mirror other analgesics and anti-pyretics but also displays unique properties that can be advantageous in certain treatment plans. Its anti-inflammatory activity is not as strong as other similar medications known as NSAIDS; fully refereed to as non-steroidal anti-inflammatory drugs. The main mechanism proposed for paracetamol involves the highly selective inhibition of an enzyme called cyclooxygenase; abbreviated COX. There are two isoenyzmes of cyclooxygenase are of similar molecular weight and structure but each take on different functions. They are labeled COX-1 and COX-2. COX-1 is present in most tissues and but functions more specifically on maintaining the lining of the stomach. It also plays other vital roles within the body such as platelet and kidney function.
Aspirin has grown so much in popularity that about 35,000 metric tons of it is produced and consumed each year to meet the consumer’s demand. 35,000 metric tons is equivalent to 100 billion standard aspirin tablets (10). That many tablets means that the market for aspirin is very good. Today, Aspirin is known as the leading non-prescription medicine of all time. It is the most common pill taken for pain, inflammation and fever. It has grown all over the world, being made available in eighty countries (9). It would not be surprising if one day, all the countries would have aspirin available to them.
Paracetamol (Acetaminophen) 500 mg, 1-2 tablets 4 hourly PRN: Analgesic with limited anti-inflammatory activity (Woo & Wynne, 2011, p. 887). Used to reduce the pain of
During the 1900's, the McNeil company developed and established Tylenol into a well known and recommended analgesic. It has become recognized world wide as a safe brand of acetaminophen. The name Tylenol has become identified as a trusted, safe drug that people can easily purchase over the counter for their ailments. Tylenol is still recommended by doctors even though there was a cyanide scare in the history of the company. It has been discovered by my independent survey that consumers use Tylenol for their pet's needs also.
Aspirin contains the substance acetylsalicylic acid (ASA), which can relieve inflammation, fever, pain, and known as a “blood thinner”. Aspirin was not officially trademarked until March 6, 1899 when the Imperial Office of Berlin made it official. It has been used for the last 110 years, but its natural form, salicylic acid has been around for thousands by Egyptians, Greeks, and Romans. Aspirin is available in over 80 countries and known as the best non-prescription drug. The most common use of aspirin is to cure headaches and use it as a pain reliever, but aspirin is known to prevent heart attack and strokes. It was first proposed in 1940, but wasn’t confirmed until 1970 when doctors would recommend taking aspirin daily [1].
In the late 1800’s it was discovered that papa-amino-phenol, could reduce fever, but the drug was too toxic to use. A less toxic extract called phenacetin was later found to be just as effective but also had pain-relieving properties. In 1949, it was learned that phenacetin was metabolized into an active but also less toxic drug, acetaminophen. Since then, acetaminophen has been sold under many over the counter brand names, most popular being Tylenol.
Percocet is a prescription drug made up of two different components; acetaminophen (pain reliever and fever reducer) and oxycodone (an opioid that binds to opioid receptors to produce morphine like effects). The initial use of percocet results in an euphoric sensation for the user. The drug causes the brain to receive a different signal about the pain and therefore will release dopamine to the body (“How Long Does Percocet Stay in your System?”). When percocet is prescribed in higher doses, the chances of addiction increases. The more frequent a patient takes percocet, the effect on the liver and kidney functions increases as well. It may result in a longer time for the drug to be fully excreted from the body (“Percocet Half-Life: How Long Does it Stay in Your System”). Once a patient becomes addicted to percocet, medical treatment may be needed in order to help the user withdraw from using the drug.
In October of 1982, Tylenol, the leading pain-killer in the United States at the time faced a crisis. Seven people in Chicago were reported dead after taking Tylenol. 12-year-old Mary Kellerdman of Elk Grove Village, Illinois, Adam Janus of Arlington Heights, Illinois, his brother Stanley Janus, and his wife Theresa Janus, Mary Reiner of Winfield, Paula Price, and Mary McFarland of Elmhurst Illinois was the last victim of the cyanide-laced Tylenol capsules. This happened bﴱᄃecause there was Extra-Strength Tylenol capsules that had been distributed and tampered with. The capsules contained 65 milligrams of cyanide. The amount necessary to kill a human is five to seven micrograms, which means that the person used 10,000 times more poison that what was needed.. The tampering had occurred when the products reached the shelves. The connection between the deaths and the Tylenol was discovered within days by two off-duty firemen who were listing to their police radios. Phillip Cappitelli and Richard Keyworth were the men to make the connection and tell there superiors.
Also it will act with n-octanol because of the non-polar hydrocarbons. Aspirin has acidic functional group so it will also react with NaOH to form a salt (carboxylate ion) and it will interact with n-octanol also same as paracetamol in addition of presence of ester which lipophilic. Phenyl butazone contains acidic functional group (β-Dicarbonyl) which will interact with NaOH to give a salt (–OCO-). Also there will be interaction with HNO3 by tertiary amine which will give NH+. In n-octanol will be a reaction because of the hydrocarbon molecule. In Diclofenac there is interaction with NaOH by carboxylic acid to give a salt (carboxylate ion) and the aromatic amine with HNO3 to give (NH2+) also with n-octanol as there are hydrocarbons. Piroxicam there is interaction with NaOH with amide to give (N--C=O) and interaction with HNO3 with secondary amine (NH+) as well as interaction with n-octanol because of the hydrocarbons. Oxaprozin has carboxylic acid which react with NaOH to give (Carboxylate ion) and it has secondary amine which reacts with HNO3 to give (NH+) plus interaction with n-octanol as there are hydrocarbons and
Quinine, a special anti-parasite used in pills and tonic water, and gives it a unique bitter taste. It was a common product in the over the counter pharmacy product until it was banned by the Food and Drug Administration. Why? The side effects of the pill could be deadly unless used under professional medical attention. Yet it’s still used in tonic water? To find out why we have to go deeper into the topic of quinine and it’s history.
The Tylenol crisis occurred in October of 1982 when seven people died in Chicago after immediately taking extra-strength Tylenol capsules. Tylenol was the leading non-prescription pain reliever medicine at that time. The capsules were popular in particular because they were slicker and easier to swallow. It was later found out that the capsules that were taken by these people were laced with a very lethal dose of cyanide. The Tylenol brand name is owned by McNeil Consumer Healthcare which is a subsidiary of Johnson & Johnson. The company Johnson & Johnson established that the cyanide lacing happened after the Tylenol cases already left the factory. Food and Drug Administration officials hypothesized that the culprit took Extra-Strength Tylenol
Ketamine Hydrochloride is an anethetic developed in 1962 by Dr Calvin Stevens. In the 1960's and 1970's, it was used on the battlefields of the Vietnam War. It had a strong painkilling effect, that did not affect the patients breathing. It's currently used as a human anesthetic and in veterinary medicine, most commonly used on horses. In its illegal form, ketmine is used to get high or even used for drink spiking.
Ropivacaine is homologous to Bupivacaine . If local anaesthetics are administered into the vein or artery it results to very high systemic levels possibly causing CNS and CV toxicity due to rapid penetration into these regions. Both bupivacaine and ropivacaine are amide linked esters. They are extensively bound in the plasma. Amides extensively bind to the alpha-1 acid glycoprotein (AAG) with ~94% ropivacaine bound to it; it has a higher affinity even though albumin binds to greater amount due to its relative abundance in the human plasma. AAG concentration increases after operative surgery. Ropivacaine is metabolised by the cytochrome P450 isoenzymes CYP1A2 and CYP3A4 to four metabolites, 3-OH-2’6’-pipecoloxylidide, 4-OH-ropivacaine, 3-OH-ropivacaine, and N-dealkylated PPX. Reduced protein binding means that there is higher fraction of the unbound drug circulating in the plasma. Furthermore, amides are hepatically metabolised by amidases. Amidase metabolism is much slower than plasma hydrolysis in which ester linked local anaesthetics undergo. This means that amides are prone to accumulation when administered by continuous infusion. Drug accumulation is also influenced by reduced hepatic perfusion and hepatic dysfunction. It has been reported that high concentrations of unbound bupivacaine are linked with higher rates of early symptoms of CNS toxicity.
Thus, foreign substances undergo so-called first-pass metabolism before they reach other organs in the body. Some hepatotoxins, including carbon tetrachloride (CCl4) and many commonly used drugs, directly cause damage to hepatocytes. However, other toxins become toxic only as a result of enzymatic modification by the liver’s detoxification machinery—the Cytochrome P450 enzymes. For example, acetaminophen (Tylenol) has no toxic properties by itself but becomes noxious upon conversion to the mitochondrial toxin NAPQI (N-acetyl-p-benzoquinone imine) through the activity of the P4502E1 enzyme (14). Toxins can cause injury to hepatocytes, BECs, or both. Cytochrome P450 enzymes are most abundant in zone 3 hepatocytes, accounting for the higher rate of drug toxicity in that portion of the lobule. Toxins can cause either acute or chronic damage, with the most common offenders being alcohol, acetaminophen, galactosamine, CCl4, antibiotics, and nonsteroidal anti-inflammatory
Tylenol's 1982 ordeal has become a classic example of a successful crisis management. Johnson & Johnson faced a major crisis when their leading pain-killer medicine, extra-strength Tylenol, was found to have caused the fatalities of seven people in Chicago, Illinois. It was reported that unknown suspect or suspects took the product off store shelves, tampered it with deadly cyanide and returned to the shelves. As a result, seven people died and consumers lost confidence and panicked over hearing the news of this incident. Tylenol received massive media coverage which led to an expeditious communication of event to the public. Johnson & Johnson (J & J) took a huge financial hit when it had to recall and destroy approximately $100 million dollars worth of inventory in addition to the loss incurred by the company when the public reacted to the incident (Campbell et. al., n.d.). Tylenol's approach was to pull off the products as quickly as possible, stopped production, cooperated with the investigation and the media and halted all forms of advertisement or marketing of the product. Furthermore, Johnson's & Johnson's took the initiative to protect and improve their product packaging which allowed them to regain the public's confidence and paved the way for improved tamper-resistant packaging now used by myriad of manufacturing companies. The fatalities occurred between September 29th to October 1st of the year 1982 and by November, Tylenol had already reintroduced the product with improved tamper-resistant packaging. To regain the public's attention and confidence, Johnson's & Johnson's launched a dynamic marketing campaign to put the product's name before the public.