Aspirin Research Project

http://www.sigmaaldrich.com/content/dam/sigma-aldrich/structure1/180/mfcd00002430.eps/_jcr_content/renditions/mfcd00002430-medium.png

+ NaHCO3 → + CO2 + H2O

C9H8O4 + NaHCO3 → C9H7NaO4 + CO2 + H2O

+ → + +

(Aus-e-tute, 2013)

C:\Users\jimmy\Downloads\13148463_1074591792600041_117913831_o.jpg

Social and Environmental Perspectives

Aspirin is a fundamental drug in society as it reduces pain, fever and inflammation (Flower, 2003). It achieves this through the inhibition of the production of prostaglandins which are lipid autacoids (unsaturated carboxylic acids) that cause pain, inflammation and fevers (Ophardt, 2003). Hence, aspirin inhibits prostaglandin production as it blocks the enzyme cyclooxygenase (COX) through its acetyl group, in hydrolysis being the reaction of breaking a bond of a molecule in water, bonding to the alcohol group of serine in the enzyme (Ophardt, 2003). In effect, this blocks the channel of the enzyme preventing arachidonic acid from entering it and producing prostaglandin (Ophardt, 2003). Figure 4 reflects this effect aspirin has on the enzyme. Thus, due to these effects, aspirin is utilised globally as the reduction of these health risks are undoubtedly beneficial to individuals within society. http://chemistry.elmhurst.edu/vchembook/images/556coxaspirin.gif

Similarly, aspirin also has the benefit of reducing heart attacks. This is due to the nature of heart attacks being caused by a blood clot which stop blood flow (Ricciotti & FitzGerald, 2012). As such, aspirin prevents the formation of prostaglandins which aggregate platelet flow that clot blood (Ricciotti & FitzGerald, 2012). Hence, by preventing platelets from clotting blood the risk of heart attacks is reduced.

Also, aspirin is vital in society as it generates revenue. For instance, within the company of ‘Bayers’ alone aspirin sold produced a total revenue of €494 million in 2012 (Statista, 2016). This amount reflects how significant aspirin is in the pharmacy industry and hence provides the pharmacy industry with money necessary to provide jobs with regards to the production and distribution of aspirin. In turn, aspirin is vital in society in providing jobs for individuals. Similarly, due to the sales of aspirin the economy is benefitted as its sales circulate large amounts of money through society (unknown, 2012).

Conversely, aspirin also presents a variety of different health risks. One of which is due to aspirin’s mechanism of thinning blood which increases the probability of haemorrhagic strokes (Gorelick & Weisman, 2005). This risk is most prominent in large dosages and raises fatal health concerns for patients. Likewise, aspirin also poses the health risks of nausea, vomiting, and decreased hearing which although reversible are common (Mayo Clinic Staff, 2015). Alternatively, a long-term effect of inducing constant amounts of aspirin is that it can irritate the stomach and intestines which can lead to the development of ulcers (PBS NewsHour, 2012). Furthermore, aspirin is linked with the development of Reye’s syndrome in children and adolescents when utilised during viral infections such as chickenpox or influenza (Weiner, 2015). This disease, although rare, induces symptoms of mental changes and uncontrolled vomiting (Weiner, 2015). However, may also lead to the death or permanent brain damage with an estimate of 25% progressing to coma (Weiner, 2015).

Likewise, a social issue associated with aspirin is the cost of it. Specifically, within 3rd world countries such as India the price of aspirin can be deemed as rather expensive when contrasting to the level of poverty present (unknown, 2012). Hence, patients who are in need of the medication may be unable to obtain it simply because they lack the money to do so.

Furthermore, aspirin’s production also raises issues regarding the environment. Every year the mass production of aspirin constitutes to the production of approximately 100+ billion tablets (unknown, 2012). Hence, this mass production raises implications with regards to the resources utilised for its packaging and production and also the pollution emitted as a result. Specifically, plastic is a resource utilised within the packaging process that degrades the environment whilst a chemical released during the production process is acetic acid (CH3COOH) which in large quantities raises issues as it is toxic to aquatic wild life (Kegley, Choi, & Hill, 2014). Thus, the pollution reaches the environment which therefore induces detrimental effects upon the wild life present (KwikMed, 2011). Figure 5 reflects the path of pharmaceutical tablets into the environment. Moreover, an example of a detrimental effects associated upon the wildlife due to pharmaceutical pollution is the reduction to fertility or development upon fish (Murdoch, 2015). This issue of pollution is only increasing with time as due to population increase; the demand for aspirin increases hence more is produced therefore heightening the environmental issues associated.

Conclusion

Conclusively, aspirin possesses a range of different advantages whilst also producing adverse effects with its usage. In elaboration, the main advantages which aspirin presents is that it reduces inflammation, fevers, pain and also the risks of heart attacks. Similarly, it is advantageous to society as it generates revenue to fund the jobs of individuals. Alternatively, aspirin’s usage produces adverse effects of increasing the risk of haemorrhagic strokes, nausea, vomiting, decreased hearing, development of ulcers and Reye’s syndrome. Furthermore, its production and distribution also produces detrimental effects to the environment. Hence, a suggestion is to the management of aspirin is to restrict its usage to only being a last resort. As there are other alternatives to aspirin being naproxen or ibuprofen which do not possess the detrimental health effects of aspirin. Furthermore, pharmaceutical companies should strive to become environmentally friendly in their processes as the environment should undoubtedly be preserved. In future, it is most likely that better alternatives will developed and thus should be utilised instead of aspirin as it is ideal to not comprise the health of patients at all.

Bibliography

Videos

Let Learn Science. (2012, March 15). 5. Acid Cataylst and Esterification (HSC) Chemistry. Retrieved April 13, 2016, from Youtube: https://www.youtube.com/watch?v=_lz9dROgHDs

PBS NewsHour. (2012, March 21). How Aspirin May Help Prevent Certain Kinds of Cancer. Retrieved April 15, 2016, from Youtube: https://www.youtube.com/watch?v=_yJp6DVQa6c

Online Journal

Flower, R. (2003). What are all things aspirin does? The BMJ, 572-573.

Gorelick, P. B., & Weisman, S. M. (2005). Risk of hemorrhagic stroke with aspirin use. Stroke, 1801-1807.

Ricciotti, E., & FitzGerald, G. A. (2012). Prostaglandins and Inflammation. Arteriosclerosis, Thrombosis, and Vascular Biology, 986-1000.

Books

Evans, C., McCann, M., & Morton, B. (2012). Chemistry Workbook. Adelaide: Greg Eather.

Royal Society of Chemistry. (2003). Aspirin. London: Royal Society of Chemistry.

Websites

Aus-e-tute. (2013). Aspirin (Acetylsalicylic acid). Retrieved April 11, 2016, from Aus-e-tute: http://www.ausetute.com.au/aspirin.html

Brown, W. H. (2016, February 3). Salicylic Acid. Retrieved April 10, 2016, from Encyclopedia Britannica: http://www.britannica.com/science/salicylic-acid

International Aspirin Foundation. (2016). The Chemistry of Aspirin. Retrieved April 3, 2016, from Increasing the Knowledge & Understanding of Aspirin: http://www.aspirin-foundation.com/history-of-aspirin/the-chemistry-of-aspirin/

Kegley, S., Choi, A., & Hill, B. (2014). Acetic acid. Retrieved April 23, 2016, from PAN Pesticides Database - Chemicals: http://www.pesticideinfo.org/Detail_Chemical.jsp?Rec_Id=PC32883#Ecotoxicity

KwikMed. (2011). The Environmental Impacts of the Pharmaceuticals Industry and the way forward. Retrieved April 14, 2016, from Kwikmed: https://www.kwikmed.org/environmental-impact-pharmaceutical-industry/

Mayo Clinic Staff. (2015, November 3). Daily aspirin therapy: Understand the benefits and risks. Retrieved April 15, 2016, from Mayo Clinic: http://www.mayoclinic.org/diseases-conditions/heart-disease/in-depth/daily-aspirin-therapy/art-20046797

Ophardt, C. E. (2003). Prostaglandins. Retrieved April 14, 2016, from Virtual Chembook: http://chemistry.elmhurst.edu/vchembook/555prostagland.html

Pillai, S. G. (2015, May 3). Introduction to Preparation of Salicylic Acid. Retrieved April 10, 2015, from Slide Share: http://www.slideshare.net/yagnesh96/introduction-and-preparation-of-salicylic-acid

Statista. (2016). Bayer AG's top pharmaceutical products from 2010 to 2015, based on revenue (in million euros). Retrieved April 13, 2016, from Statista: http://www.statista.com/statistics/263787/revenues-of-bayers-top-pharmaceutical-products/

unknown. (2012, June 11). Aspirin Should it be the Ideal Medicine. Retrieved April 13, 2016, from Aspirin Positive Negative Effects: http://aspirinpositivenegativeeffects.weebly.com/blog.html

Weiner, D. L. (2015, April 2). Reye Syndrome. Retrieved April 15, 2016, from Medscape: http://emedicine.medscape.com/article/803683-overview

Article

Murdoch, K. (2015, May). Pharmaceutical Pollution in the Environment:Issues for Australia, New Zealand and. National Toxics Network, pp. 5-9.

Images for equations

Galtra Inc, (2014), Phenol Chemical Structure [ONLINE]. Available at:http://www.galtra.net/v2/index.php/intermediates/86-phenol [Accessed 9 April 2016].

Lukáš Mižoch, (2006), Acetic Anhydride Chemical Structure [ONLINE]. Available at:https://commons.wikimedia.org/wiki/File:Acetic_anhydride.svg [Accessed 11 April 2016].

Merck Millipore, (2016), Sodium Salicylate Chemical Structure [ONLINE]. Available at:http://www.merckmillipore.com/GT/en/product/Sodium-Salicylate---CAS-54-21-7---Calbiochem,EMD_BIO-567630 [Accessed 10 April 2016].

Sigma Aldrich, (2016), Acetylsalicylic acid Chemical Structure [ONLINE]. Available at:http://www.sigmaaldrich.com/catalog/product/sigma/a5376?lang=en®ion=AU [Accessed 11 April 2016].

Sigma Aldrich, (2016), Sodium Phenoxide Chemical Structure [ONLINE]. Available at:http://www.sigmaaldrich.com/catalog/product/aldrich/cds001581?lang=en®ion=AU [Accessed 11 April 2016].

Yikrazuul, (2009), Salicylic Acid Chemical Structure [ONLINE]. Available at:https://commons.wikimedia.org/wiki/File:Salicylic_Acid.svg [Accessed 10 April 2016].

Images

Charles E Ophardt, (2003), Aspirin effect on COX Enzyme Necessary for Prostaglandin Production[ONLINE]. Available at: http://chemistry.elmhurst.edu/vchembook/555prostagland.htmlaspirin [Accessed 12 April 2016].

Jim Clark, (2013), Energy Profile Diagram reflecting effect of Catalyst [ONLINE]. Available at:http://www.chemguide.co.uk/physical/basicrates/catalyst.html [Accessed 10 April 2016]

Kristie Murdoch, (2015), Pathway of Pharmaceuticals into the environment [ONLINE]. Available at:http://www.ntn.org.au/wp/wp-content/uploads/2015/05/NTN-Pharmaceutical-Pollution-in-the-Environment-2015-05.pdf [Accessed 29 April 2016].

Wikipedia, (2014), Chemical Structure of Aspirin [ONLINE]. Available at:https://en.wikibooks.org/wiki/Structural_Biochemistry/Aspirin [Accessed 9 April 2016].

Student response

Research skills

Information source

(correctly formatted reference)

Flower, R, 2003. What are all the things that aspirin does?. The BMJ, [Online]. 327, 572-573. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC194070/ [Accessed 14 April 2016].

Relevant information highlighted in materials submitted

Communication

Description of information

The information provided is an extract from an esteemed online medical journal known as ‘the BMJ.’

Analysis

Relevance

(the degree to which the source addresses the topic)

The source is reasonably relevant in highlighting the key usages and effects of aspirin. Furthermore, it is relevant in detailing some chemistry related to aspirin. However, it integrates complex biological concepts into its explanations which aren’t relevant.

Possibility of bias

(evidence of a prejudiced or partial viewpoint that influences interpretation of the material)

The information is objectively presenting the facts related to aspirin hence it’s not very bias. However, as the author is from a pharmaceutical background he may try to skew the information in favour of the aspirin hence there may be some bias. Alternatively, as it is a part of a medical journal, its content’s would have been reviewed to prevent it from being overly biased.

Credibility

(the trustworthiness, i.e. credentials, education, experience, peer review etc. of the source)

The author is a professor of biochemical pharmacology hence has the appropriate credentials to provide credible information. Furthermore, as it is from a renowned medical journal it further support’s its credibility.

Other factors

(ease of access, clarity of language and presentation, use of diagrams)

Source Analysis- Source 1

Source 1

Ask any medical student and he or she will tell you that aspirin reduces fever, pain, and inflammation but may cause ulcers. Students may also recollect that it prolongs bleeding, and may prevent strokes and heart attacks, but would be unlikely to know of its use in cancer or Alzheimer's disease.

A defining point in the history of aspirin was the discovery that it inhibited the prostaglandin forming cyclooxygenase.1 Prostaglandins cause inflammation, fever, and pain; have gastric cytoprotective actions; and are implicated in platelet aggregation, so this discovery provided a unified explanation for the effects of aspirin (and most other non-steroidal anti-inflammatory drugs). However, events took an even more interesting turn when a further isoform of cyclo-oxygenase, cyclooxygenase-2, was discovered.2 While similar in many ways to the original enzyme (COX 1) there were important differences, including the fact that COX 2 was induced in cells by inflammatory insults. COX 2 therefore seemed to be the most relevant target in inflammation, which led to the notion that the constitutive COX 1 generated prostaglandins required to maintain physiological functions (such as protection of the gastric mucosa, platelet aggregation) whereas COX 2 generated pro-inflammatory mediators.3 Aspirin inhibited both isoforms, as did most non-steroidal anti-inflammatory drugs, perhaps explaining why these compounds were not only effective therapeutically but also had characteristic side effects.

The ensuing search by the pharmaceutical industry for selective COX 2 inhibitors culminated in the recent introduction of new, safer anti-inflammatory drugs as well as the rediscovery of older drugs that had COX 2 selective actions. But, as aspirin inhibits both isoforms, why does it continue to be used and why is there continuing interest in its pharmacology?

The answer to the first part of this question is partly down to aspirin's unique mechanism of action that inhibits both COX 1 and COX 2 irreversibly. The effects of this are evident in platelets where cyclo-oxygenase cannot be replaced, explaining why a single aspirin can depress platelet aggregation for many days. The half life of aspirin in plasma is short; esterases remove the acetyl group leaving free salicylate, which may have a secondary pharmacological effect through cyclooxygenase inhibition or other mechanism, adding to the complexity of aspirin's action.

The current interest in aspirin stems from the fact that many animal experiments and human epidemio-logical studies now link aspirin (and other non-steroidal anti-inflammatory drugs) with beneficial effects in various cancers, including breast, ovarian, oesophageal, and colorectal cancer. Recent meta-analyses supported the idea that the overall relative risk of colorectal cancer is reduced in people taking long term aspirin.4 Another meta-analysis of observational data confirmed a protective effect in oesophageal cancer and provided evidence of a relation with dose and duration of treatment, and other studies showed a beneficial effect in ovarian cancer.4,5 How aspirin or other non-steroidal anti-inflammatory drugs produce this effect is not entirely clear, but the synthesis or activity of COX 2 is increased in many tumours, and inhibition could activate apoptotic mechanisms or suppress angiogenesis.6 It has even been suggested that the link between diet and the prevention of colorectal cancer is attributable to the presence of salicylic acid in plant and vegetable foodstuffs.7

Evidence from longitudinal studies of long term users of non-steroidal anti-inflammatory drugs originally pointed to a reduced risk of Alzheimer's disease,8 and these findings are supported by other, more recent data,9 where an inverse relation was found between taking aspirin (and other non-steroidal anti-inflammatory drugs) and Alzheimer's disease, but not other forms of dementia. The mechanism is uncertain—Alzheimer's has an inflammatory component and therefore COX 2 may be the target, although other mechanisms have been suggested.10

Two questions bedevil what is otherwise an exciting therapeutic prospect. What is the minimum dose required to achieve these effects, and how can we assess the relative risk and benefit of a preventive treatment that will entail treating healthy people for many years with a drug known to have gastric and other side effects? It is here that aspirin's grandchildren may have a role. COX 2 seems to be the main culprit in both cancer and Alzheimer's, so the selective COX 2 inhibitors, which have reduced gastric side effects, are natural choices for such long term prophylactic treatment.

What of the future of aspirin itself? Because of its profound effects on platelets it is unlikely to be supplanted as a cheap and effective prophylactic treatment for those patients at risk from excessive platelet aggregation, but in view of its venerable history, it is surprising that aspirin is still the subject of ongoing medicinal chemistry effort. Attaching a nitric oxide donor to the molecule seems to ameliorate the side effects of the drug while boosting its therapeutic effects.11 The discovery of a third form of cyclooxygenase,12 mainly confined to the central nervous system and heart, which is also inhibited by aspirin, will no doubt provide yet another twist to the continuing story of this fascinating but simple drug.

________________

Student response

Research skills

Information source

(correctly formatted reference)

AUS-e-TUTE. 2013. Aspirin (acetylsalicylic acid). [ONLINE] Available at:http://www.ausetute.com.au/aspirin.html. [Accessed 11 May 2016].

Relevant information highlighted in materials submitted

Communication

Description of information

The information is from a science website.

Analysis

Relevance

(the degree to which the source addresses the topic)

All of the information provided is highly relevant with regards to the chemistry aspect of aspirin. Specifically, it details equations which are highly relevant to the chemistry of aspirin.

Possibility of bias

(evidence of a prejudiced or partial viewpoint that influences interpretation of the material)

The information provided is entirely factual hence would most likely not possess bias as there are no personal opinions integrated. The authors are multiple science teachers from the website hence it would possess an array of different viewpoints to prevent bias.

Credibility

(the trustworthiness, i.e. credentials, education, experience, peer review etc. of the source)

The authors’ details and credentials are not presented hence credibility cannot be accounted for in that regard. However, the website is entirely dedicated to chemistry and produced by a group of science teachers hence would’ve been peer assessed to suggest some credibility.

Other factors

(ease of access, clarity of language and presentation, use of diagrams)

The diagrams on equations are useful.

Source Analysis- Source 2

key Concepts

* Aspirin is widely used as an analgesic (pain reliever) and an antipyretic (for reducing fever). It is also used to help prevent heart attacks, strokes, and blood clot formation in people at risk of developing blood clots.

* Aspirin (acetylsalicylic acid) is an aromatic compound containing both a carboxylic acid functional group and an ester functional group.

* Aspirin is a weak acid that is only slightly soluble in water.

* Aspirin can be prepared by reacting salicylic acid and acetic anhydride in the presence of an acid catalyst.

Structure of Aspirin (acetylsalicylic acid)

Aspirin (acetylsalicylic acid) contains three groups: http://www.ausetute.com.au/images/aspirinfg.gif

* carboxylic acid functional group (R-COOH)

* ester functional group (R-O-CO-R')

* aromatic group (benzene ring)

Properties of Aspirin (acetylsalicylic acid)

Acidity

Aspirin is a monoprotic weak acid, Ka = 2.8 x 10-4 at 25oC, so very little of the molecular aspirin (acetylsalicylic acid) dissociates to form acetylsalicylate ions.

For the equilibrium dissociation reaction:

aspirin (acetylsalicylic acid)

http://www.ausetute.com.au/images/eqlarrow.gif

acetylsalicylate ion

+

H+

http://www.ausetute.com.au/images/aspirin.gif

http://www.ausetute.com.au/images/eqlarrow.gif

http://www.ausetute.com.au/images/aspirinneg.gif

+

H+

the equilibrium position lies well to the left, favouring molecular aspirin.

Solubility

Aspirin is only slightly soluble in water and acidic solutions such as is present in the stomach. Aspirin contains polar functional groups which can form hydrogen bonds with polar water molecules.

Aspirin is more soluble in basic (alkaline) solutions, so it readily dissolves in the duodenum which is the first part of the intestine.

Ionic salts of aspirin, such as sodium acetylsalicylate, are more soluble in water since they form stronger ion-dipole interactions with water.

These ionic salts of aspirin are sometimes marketed as "soluble aspirin". When you add water to the soluble aspirin, eg, sodium acetylsalicylate, it dissociates to form sodium ions and acetylsalicylate ions:

sodium acetylsalicylate

→

acetylsalicylate ions

+

sodium ions

http://www.ausetute.com.au/images/aspirinna.gif

→

http://www.ausetute.com.au/images/aspirinneg.gif

+

Na+

C9H7O4-Na+

→

C9H7O4-

+

Na+

In the acidic stomach, molecular aspirin crystallizes out:

acetylsalicylate ions

+

H+

→

aspirin

http://www.ausetute.com.au/images/aspirinneg.gif

+

H+

→

http://www.ausetute.com.au/images/aspirin.gif

C9H7O4-

+

H+

→

C9H8O4

Preparation of Aspirin (acetylsalicylic acid)

Salicylic acid will rapidly react with acetic anhydride in the presence of an acid catalyst to produce aspirin (acetylsalicylic acid) and acetic acid (ethanoic acid).

Sulfuric acid or phosphoric acid are often used to catalyse the reaction.

salicylic acid

+

acetic anhydride

(ethanoic anhydride)

[H2SO4]

→

aspirin

(acetylsalicylic acid)

+

acetic acid

(ethanoic acid)

http://www.ausetute.com.au/images/saliacid.gif

+

http://www.ausetute.com.au/images/ethanhyd.gif

[H2SO4]

→

http://www.ausetute.com.au/images/aspirin.gif

+

CH3COOH

C7H6O3(s)

+

C4H6O3(l)

[H2SO4]

→

C9H8O4(s)

+

C2H4O2(aq)

Salicylic acid can react with acetic (ethanoic) acid in an esterification reaction, but the reaction is very slow, taking days to reach equilibrium, and the yield is low:

salicylic acid

+

acetic acid

(ethanoic acid)

[H2SO4]

→

aspirin

(acetylsalicylic acid)

+

water

http://www.ausetute.com.au/images/saliacid.gif

+

CH3COOH

[H2SO4]

→

http://www.ausetute.com.au/images/aspirin.gif

+

H2O

C7H6O3

+

C2H4O2

[H2SO4]

→

C9H8O4(s)

+

H2O

For this reason, the commercial preparation of aspirin relies on the faster reaction between salicylic acid and the more reactive acetic anhydride which produces a greater yield of aspirin.

Reactions of Aspirin (acetylsalicylic acid)

. Neutralization: acid + base → salt + water

aspirin

(acetylsalicylic acid)

+

sodium

hydroxide

→

a salt

(sodium acetylsalicylate)

+

water

http://www.ausetute.com.au/images/aspirin.gif

+

NaOH(aq)

→

http://www.ausetute.com.au/images/aspirinna.gif

+

H2O(l)

C9H8O4(s)

+

NaOH(aq)

→

C9H7O4(s)-Na+

+

H2O(l)

1. The neutralization reaction can be used to determine the amount of aspirin (acetylsalicylic acid) present in commercially available aspirin tablets using a back (indirect) titration method.

2. Reaction with carbonate: acid + carbonate → salt + carbon dioxide + water

aspirin

(acetylsalicylic acid)

+

sodium

hydrogen

carbonate

→

a salt

(sodium acetylsalicylate)

+

carbon

dioxide

gas

+

water

http://www.ausetute.com.au/images/aspirin.gif

+

NaHCO3(aq)

→

http://www.ausetute.com.au/images/aspirinna.gif

+

CO2(g)

+

H2O(l)

C9H8O4(s)

+

NaHCO3(aq)

→

C9H7O4(s)-Na+

+

CO2(g)

+

H2O(l)

1. The reaction with bicarbonate (hydrogen carbonate ion) is commonly used to prepare the salt of aspirin which is more soluble in water than the molecular form of aspirin.

2. Hydrolysis: cleavage of a covalent bond in a molecule by reaction with water

aspirin

(acetylsalicylic acid)

+

water

→

salicylic acid

+

acetic acid

(ethanoic acid)

http://www.ausetute.com.au/images/aspirin.gif

+

H2O(l)

→

http://www.ausetute.com.au/images/saliacid.gif

+

CH3COOH(aq)

C9H8O4(s)

+

H2O(l)

→

C7H6O3(s)

+

C2H4O2(aq)

1. Old aspirin tablets may have a smell like vinegar as a result of the hydrolysis reaction producing acetic acid (ethanoic acid).

Page |