Paracetamol: History, Structure and Dangers

Paracetamol History, Structure and DangersWhat is Paracetamol?Depending on where you live in the world, N-(4-hydroxyphenyl)ethanamide is known as Paracetamol or acetaminophen with the molecular formula of C8H9NO2. Paracetamol or acetaminophen belongs to a group of medical specialtys which have analgesic ( botheration reliever) and febrifuge (fever reliever) properties. For these reasons it is used for reliving a person of loco to moderate pain including headache, joint pain and toothache. In Addition to controlling fever (high temperature) Paracetamol can also be used to relive symptoms of cold.History of ParacetamolThe write up and uncovering of Paracetamol is fascinating as it was discovered by accident when a similar molecule acetanilide was put to use as an analgesic and antipyretic medicine in the late 1800s.At the approach of 20th century the breakthrough and entailment of medicine was based on pure chance, as scientists promiscuously tested new mixeds on test subjects (mainly humans, without any awareness of their possible incline effects) to examine both their positive and negative effects. The discovery of Paracetamol can be linked with the discovery of acetanilide which was the first derivative of aniline (see figure 1.1) to be found to contain analgesic and antipyretic properties. betoken 1.1 shows the structure of the total compound anilineAcetanilide was synthesised when the aniline gained a secondary amide group. This occurred when aniline was reacted with ethanoic anhydride, resulting in the production of C8H6NCOCH3 and CH3COOH (ethanoic acid). The equation for the reaction is as follows C6H5NH2 + (CH3CO)2O C6H5NHCOCH3 + CH3COOHSoon after the discovery acetanilide (see Figure 1.2) was produced to be used in therapy in 1886, and it remained in use for several years due to how cheap it was to mass produce. The painkilling properties of the synthetic extreme compound acetanilide were impressive but it had to be abandoned due its high to xicity in moderate doses. For example, it was known to interfere with the function of the oxygen-carrying rouge haemoglobin which caused cyanosis in patients.Figure 1.2 shows the structure of the organic compound acetanilideAs a result a new search began which lead to the discovery of a new derivative called N-4-(-Ethoxyphenyl)ethanamide(see figure 1.3). To their surprise the new derivative contained the same analgesic and antipyretic properties but was less toxic than acetanilide. The first synthesis was reported in 1878 by Harmon Northrop Morse (3). It wasnt until 1886 that this new drug was marketed under the name phenacetin. It remains in use ever since but the engagement has declined due its undesirable side effects on the colored. Although Phenacetin I still being used today in some parts of the country, it was ban in USA by the FDA in 1983 after research showed it had adverse side effects such as kidney damage.Figure 1.3 shows the structure of the organic compound Phenace tinFinally, in 1893 a German physician Joseph von Mering managed to improve phenacetin resulting in the production of Paracetamol. Unfortunately, Joseph Von Mering mistakenly thought that Paracetamol had similar adverse effects as acetanilide did and therefore ignored the discovery. It wasnt until the 1940s when this misunderstanding was removed after research showed that Paracetamol was the main metabolite of phenacetin (see figure 1.4) and potentially caused the desired side effects. Further studies showed that it was the other minor metabolite that caused the negative effects and that Paracetamol was responsible for the positive effects. This finally led to Paracetamol being put to use a synthetic medicine in 1953 and its being used ever since.Today Paracetamol is manufactured by a number of different pharmaceutical companies with different brand names. In the UK merely there are more than ninety over the counter medicines which contain Paracetamol. Paracetamol is sometimes comb ined with other medicines such as decongestants (provides relief for blocked nose).Figure 1.4 Shows Paracetamol as the major metabolite (99%) of Phenacetin (5)Mechanism of actionFor reducing temperature Paracetamol is believed to act on a region of the brain called the hypothalamus which is responsible for regulation of body temperature. Paracetamol reduces pain by directly interfering with chemicals in the body called prostaglandins. These prostaglandins act much like hormones (chemical messengers) but do not move to other sites, they remain in the cell in which they were synthesised in. Prostaglandin are thought to be involved in the dilation of blood vessels which cause pain. Paracetamol is recognised by the enzyme which is responsible for the biosynthesis of prostaglandins in the body. Paracetamol inhibits the biosynthesis of prostaglandins. Therefore, reduction in the number of prostaglandin reduce the awareness to pain in the body.Dangers of ParacetamolParacetamol is a potent medicine which is easily available without any prescription, still small overdoses can be fatal, because it is metabolised into both toxic and non-toxic products in the colorful. For this reason, Paracetamol is often used as suicide drug. Paracetamol overdose can cause liver chastening because it is a hepatoxic, which means even in moderate doses it can cause damage to hepatocytes (liver cells). People who use Paracetamol as means of suicide die from liver damage and most of the poisoning is due to a metabolite of Paracetamol called quinone amine (see figure 1.5).Quinone amine is dangerously toxic and is eliminated from the body in the liver by a reaction with glutathione (a tripeptide). Insufficient levels of glutathione means the toxic quinone amine will not be eliminated and mystifys to build up. Eventually it will start to react with nucleic acids and cellular proteins in the liver causing permanent damage and eventually death.ReferencesCSID5889, http//www.chemspider.com/Che mical-Structure.5889.html (accessed 1947, Oct 31, 2014)CSID880, http//www.chemspider.com/Chemical-Structure.880.html (accessed 2047, Oct 31, 2014)H. N. Morse (1878). Ueber eine neue Darstellungsmethode der Acetylamidophenole. Berichte der deutschen chemischen Gesellschaft 11 (1) 232233. doi10.1002/cber.18780110151CSID4590, http//www.chemspider.com/Chemical-Structure.4590.html (accessed 1621, Nov 1, 2014)Ellis, Frank. Paracetamol a curriculum recource . RSC, http//www.rsc.org/learn-chemistry/content/filerepository/CMP/00/000/047/Paracetamol_web.pdf. (accessed 211, Nov 1, 2014.