Chemistry can be described as the branch of science concerned with the substances of which matter is composed, the investigation of their properties and reactions, and the use of such reactions to form new substances.
The Mechanisms and Synthesis of Aspirin
Aspirin is also known as acetylsalicylic acid (ASA). It is a salicylate drug used as an analgesic (something that relieves pain without producing anesthesia or loss of consciousness) for minor aches and pains, as an anti-inflammatory drug, and as an antipyretic to suppress fever. (Vane & Bottling 2000)
The name “Salicylic acid’ was derived from salix, which is the willow family of plants. In ancient days, salicylic acids were derived from the extracts of willow bark. In today’s world, the salicylic acid is administered in the form of aspirin which is not irritating to the stomach, unlike the salicylic acid. Aspirins are prepared by reacting salicylic acid with an excess of acetic anhydride. The reaction is usually sped up by a strong acid catalyst. The aspirin product will then precipitate out when water is added due to its insolubility in water. An example of a typical aspirin reaction is shown below
(The Synthesis of Aspirin n.d.)
The aspirin product in the above example is not a purified product yet, a purified product will be gotten via the recrystallization of the aspirin product in hot ethanol. The melting point of pure aspirin is 138-140 oC.
Aspirins performs two types of actions in the human body. Aspirin works as an anti-prostaglandin, i.e., as a pain reliever, fever reducing, and as an anti-inflammation agent. Secondly, aspirin works as an anti-platelet i.e. blood thinning agent. These two actions are based on the resulting actions of aspirin on the human enzyme known as Cyclo-Oxygenase (COX). As the inflammation occurs in an injured body, as part of the natural healing process, several cells (white blood cells for instance), mediators, and enzymes helps to facilitate this inflammation. Cyclo-Oxygenase (COX) is among the enzymes in inflammation and is responsible for the formation of prostaglandins, which are group of inflammatory mediators. What aspirins, therefore, do is to inhibit the COX and thereby stopping prostaglandins from forming, this explains its anti-inflammatory quality. Also, aspiring works as a blood thinning agent due to the fact COX plays a role in the cessation of bleeding. Blood clotting occurs as a result of complex mechanisms that involve various cells which includes platelets. As a result of diseases or damage to the blood vessels, platelets clump together over the vessel tear or hole in order to facilitate the repair of the damaged part. The role of the COX is to activate thromboxane A2, a chemical that makes platelet stick together and form a plug over the damaged part. It is this sticking together of platelets, in concert with the clotting process, that creates a fibrin clot which stops the bleeding and enhances the blood vessel repair. When aspirin gets introduced into the system, it inhibits the COX which results in the reduction of the platelet’s ability to aggregate. This explains why aspirin is also known as an anti-platelet (blood thinning) agent and also why aspirin is so useful in preventing strokes and heart attacks. Aspirins leads to stomach or peptic ulcers. This is owing to the fact that aspirins inhibits the formation of prostaglandins which in turn depletes the stomach’s protective barrier and thereby leads to peptic or stomach ulcers. This mechanism by which aspirin exerts its anti-inflammatory, analgesic and antipyretic was discovered in 1971 by Vane. (Vane 1971, Roth & Majerus 1975. Smith & Willis 1971,
The Mechanisms and Synthesis of Paracetamol
Paracetamol is also known as acetaminophen. It is classified has a mild analgesic. Though it is sometimes used for the treatment of inflammatory flame, it is not classified as an NSAID (Non-steroidal anti-inflammatory drug) because it has a weak anti-inflammatory property.
Paracetamol has always been believed to be a weak inhibitor of the synthesis of prostaglandins, but, surprisingly, it has vivo effects that are similar to those of the COX-2 inhibitors. While both paracetamol and other selective COX-2 inhibitors, taking aspirin for instance, decreases the concentration of PG in vivo, paracetamol does not suppress the inflammation of rheumatoid arthritis. (Graham & Scott 2005). Paracetamol is not a strong inhibitor of prostaglandins of COX-1 and COX-2 in broken cells system, but, however, in intact cells, the synthesis of prostaglandins are usually inhibited by therapeutic concentrations of paracetamol in vitro when the levels of the substrate arachidonic acid goes below 5 mol/L. At this low levels of arachidonic acid, prostaglandins are synthesized largely by COX-2 in cells that comprise both the COX-1 and the COX-2. It can, therefore, be said that the superficial selectivity of paracetamol is as a result of the inhibition of COX-2-dependent pathways which proceed at low rates. This is also in accordance with the pharmacological effects of paracetamol and the selective COX-2 inhibitors. The site of action of paracetamol has been suggested to be COX-3, a modified version of COX-1. (Chandrasekharan et al 1999). However, evidences have shown that the analgesic effect of paracetamol is central and is due to activation of descending serotonergic pathways. The action of paracetamol at the molecular level is still yet to be known. (Botting 2000)
The Synthesis of Paracetamol
Paracetamol can be synthesized by nitrating a phenol with sodium nitrate; the desired p-nitrophenol will be separated from the ortho- byproduct and nitro group is reduced using the sodium borohydride in the laboratory process or hydrogenation in the laboratory process. Acetic anhydride is then added to the resulting p-aminophenol.
(Synthesis of paracetamol from phenol n.d.)
It can also be synthesized in a much simpler way by the direct acylation of phenol with acetic anhydride catalyzed by HF; hydroxylamine is used to convert ketone to a ketoxime and then acid-catalyzed with the Beckmann rearrangement to give amide.
References
Vane J.R., Botting R.M., 2000. The Mechanism of Action of Aspirin. The William Harvey
Research Institute, St. Bartholomew’s and the Royal London School of Medicine, Charterhouse Square, London EC1M 6BQ, UK.
Accessed < www.ncbi.nlm.nih.gov/pubmed/14592543>
Chandrasekharan N.V., Dai H., Roos K.L., Evanson N.K., Tomsik J., Elton T.S., 1999.
et al COX-3, a cyclooxygenase-1 variant inhibited by acetamino-phenandotheranalgesic / antipyretic drug s : cloning, structure and expression Proc Natl Acad Sci USA 99:13926 – 31. Accessed < www.ncbi.nlm.nih.gov/pubmed/12242329>
Roth G.J., Majerus P.W., 1975. The mechanism of the effect of Aspirin on human platelets:
1 Acetylation of a particulate fraction protein. Journals of Clinical Investment;56:624 – 32. Accessed <www.ncbi.nlm.nih.gov/pubmed/1159076>
Vane J.R., 1971. Inhibition of prostaglandin synthesis as a mechanism of action for Aspirin-like
drugs. National New Biology 1971;231:232 – 5
< www.ncbi.nlm.nih.gov/pubmed/ 20631416>
Smith J.B., Willis A.L., 1971. Aspirin selectively inhibits prostaglandin pro-duction in human
platelets. Nature ;231:235 – 7.
Accessed http://www.ncbi.nlm.nih.gov/pubmed/5284361
Graham G.G., Scott K.F., 2005. Mechanism of action of paracetamol.
American Journal of Theraupeutics. PMID:15662292 Jan-Feb;12(1):46-55.
Accessed http://www.ncbi.nlm.nih.gov/pubmed/15662292
Botting R. 2000. Paracetamol-inhibitable COX-2. Journal of Physiology and Pharmacology.
Dec;51(4 Pt 1):609-18. Review. PMID:11192935.
Accessed http://www.ncbi.nlm.nih.gov/pubmed/11192935
Botting R.J.,2000. The modern pharmacology of paracetamol: Therapeutic Actions,
Mechanism of Action, Metabolism, Toxicity and Recent Pharmacological Findings. Journal of Physiology and Pharmacolology: Dec; 51(4 Pt 1):609-18.
Accessed <http://www.ncbi.nlm.nih.gov/pubmed/23719833>
Graham G.G., Davies M.J., Day R.O., Mohamudally A., Scott K.F., 2013.
Inflammopharmacology. Jun; 21(3):201-32. Epub 2013 May 30.
Accessed <http://www.ncbi.nlm.nih.gov/pubmed/23719833>
Botting R.M., 2000. Mechanism of Action of Acetaminophen: Is There a Cyclooxygenase 3?
.Clinical Infectious Disease. Oct;31 Suppl 5:S202-10. Review. PMID:11113024
Accessed <http://www.ncbi.nlm.nih.gov/pubmed/11113024>
The Synthesis of aspirin, n.d. photograph, viewed 1st February 2014
<http://wwwchem.csustan.edu/consumer/aspirincons/aspirincons.htm>
The Synthesis of paracetamol, n.d. photograph viewed 1st February 2014
<http://commons.wikimedia.org/wiki/File:Synthesis_of_paracetamol_from_phenol.png>
