Aspirin: An Affordable Miracle Drug for Pain & More - Essay Sample

Introduction

Aspirin is one of the cheapest commonly used drugs in pharmaceuticals. Aspirin, a trading name for acetylsalicylic acid is a non-steroidal anti-inflammatory drug which has a wide range of pharmacological activities which include but not limited to pain reliever, analgesic, myocardial infarction treatment, and heart attack drug. Recently, it has been approved in low doses for pregnant women at high risk of developing toxemia of pregnancy (Crandon AJ et al., 1979) because it halts the onset of this complication.

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One of the most recognized mechanisms of action of aspirin is in inhibition of biosynthesis of prostaglandins. Prostaglandins are lipid-derivative synthesized from omega-3-fatty acids or arachidonic acid (Serhan C.N, 2008). During an injury, the body develops inflammatory responses which are accompanied by swelling, pain, redness, and heat. Partially, the body's immune system adopts mechanisms to control the responses. This is achieved by the production of pro-resolving lipids mediators such as proteins, lipoxins, and resolvins. Aspirin induces the production of lipid-derived mediators similar to those produced endogenously ( Serhan C.N.et al.,200).

History of Aspirin Discovery

The use of non-steroidal anti-inflammatory drugs (NSAIDS) dates far back to thousands of years. Physicians prescribed those (NSAIDS) for a wide range of conditions (Rao Pa et al.,2008 ). Aspirin (acetylsalicylic acid) is one of these oldest medications which are still in use today.

For decades, aspirin has been used as a household medication for inflammation, fever, and pain without the idea of its mechanism of action. It's until the 1970s that it was discovered aspirin suppressed the biosynthesis of eicosanoids ( Vane JR. 1971) derived from arachidonic acids like prostaglandins (Vane JR, 2008). Later research discovered that acetylation of cyclooxygenase (COX-2) by acetylsalicylic acid (aspirin) inhibited thromboxane formation hence its antithrombotic effects (Smith JB et al., 1971).

In 1979, reports of diverse actions of aspirin emerged which included its use in the prevention of cancer (Kune GA et al., 1988), cardiovascular diseases, myocardial infarction and stroke (Acheson J et al., 1988). One of the interesting discoveries in this context was the generation of aspirin-triggered lipoxins (ATLs) from arachidonic acid. Lipoxins induced by aspirin had remarkable anti-inflammatory effects.

Mechanism of Action of Aspirin

Aspirin is a member of the family of salicylates which have salicylic acid as the active agent. The active agent contains a benzene ring and two radicals; one a carboxyl and the other a hydroxyl group. In aspirin, the hydroxyl group is transformed into acetyl group to form acetylsalicylic acid which has pharmacological effects. Both components, salicylate, and acetate groups are biologically active ( Schror K. 2010), and their reaction is independent of each other at different sites (Alfonso LF et al., 2009)

The action of Aspirin In Cox Inhibition

Cyclooxygenase (COX) enzymes are enzymes involved in the biosynthesis of prostaglandins from either omega-3-polyunsaturated fatty acids or arachidoic acids ( Serhan C.N et al., 2008). These are the two isoforms of this enzyme, the COX-1 which is constitutively expressed and the COX-2 which is up-regulated by the inflammatory responses. COX-2 is induced upon tissue injury and due to other stimuli such as lipopolysaccharides.

The enzyme COX-2 isoform facilitates the biosynthesis of prostaglandins which mediate pain (Haeggsterom JZ et al., 2010). This enzyme is covalently bound by the hydroxyl group of aspirin inhibiting its function

Pain, Fever, and Inflammation

Non-steroidal anti-inflammatory drugs particularly aspirin inhibit pain through various mechanisms. Prostaglandins (PGDs) act synergistically with other mediators to sensitize nociceptors (Masferer J.L et al., 1996). The analgesic effect of aspirin in human when relieving pain is attributed to the disruption of the synthesis of prostaglandins. Study with an animal model for pain has shown positive results for aspirin in relieving pain. A study by Hanskaar 1979 showed overlapping time effect relationship for aspirin and morphine in the first phase of formation-induced pain response.

Aspirin has also proved effective in the management of inflammatory conditions like trauma, arthritis, and pain associated inflammations. At injury site, inflammatory mediators mediate vasodilation of blood vessels causing swelling of the tissues at the site. Here, prostaglandins which are vital in the process are inhibited by aspirin. Although COX-2 inhibition is the main mechanism through which aspirin induces its anti-inflammatory effects, other mechanisms have been reported to have the same effects. For instance, nuclear factor a transcription factor for pro-inflammatory proteins like chemokine and cytokines have shown a suppressive effect.

Similarly, aspirin relieves fever by inhibiting COX-2 mediated prostaglandins synthesis. Upon exposure to pathogens, the immune cells respond by releasing endogenous pyrogens like interleukins. When these pyrogens get to the brain through blood circulation, they induce synthesis of prostaglandins via cyclooxygenase in the hypothalamus. Prostaglandin E2 (PGE2) binds EP-3 receptor in the hypothalamus leading to reset in body temperature. Aspirin disrupts the process by COX-2 inhibition and therefore have proved effective in controlling the persistent rise in body temperature.

Clinical Uses in Prevention and Treatment of Cardiovascular Diseases

Cardiovascular diseases continue to be a major health problem throughout the world and particularly developing countries. The two main clinical problems associated with cardiovascular diseases are stroke and heart disease. The World Health Organisation estimated that by the year 2020 (Chockalingam A et al.) cardiovascular diseases would be a major cause of death and disabilities across the world.

In the control of cardiovascular diseases (CVDs), Aspirin's mechanism involves both inhibitions of platelet formation and aggregation. John Vans R, 1971 demonstrated the pivotal role of aspirin as the irreversible inhibition of platelet-dependent enzyme cyclooxygenase (COX) thereby preventing biosynthesis of prostaglandins. The COX-1 enzymes in the platelets generate thromboxane A2 which is a powerful activator of platelets aggregation. Therefore blocking the production of thromboxane A2 by aspirin becomes a potential antiplatelet effect (John Vane R, 1990). Moreover, platelets lack a nucleus and cannot regenerate COX. They are then an excellent target for antithrombotic therapy. Aspirin shows both immediate and long term effects on platelets (John Vane R, 2003).

In addition to these, other mechanisms of aspirin in cardiovascular diseases also works. For instance, aspirin inhibits the formation of COX-dependent vasoconstrictors, which lead to endothelial dysfunction in atherosclerosis (Hussain et al., 1998). Thus alleviation of endothelial dysfunction with aspirin improves vasodilation, reduces thrombosis and inhibits progression to atherosclerosis.

Furthermore, acetylsalicylic is beneficial to patients with coronary artery diseases because it reduces inflammatory responses in these patients (Ridker PM et al., 1997) and may inhibit the progression to atherosclerosis by protecting oxidation of low-density lipoproteins.

In the management of stroke, the international stroke trial (IST) (Sundercock P.A.G 1997) recorded a positive result with aspirin. The result from the trial suggested that aspirin therapy decreased the risk of recurrent stroke and death without significantly increasing the risk of hemorrhagic stroke (Sundercock P 1997). These results are consistent with the biochemical evidence in platelet activation.

Conclusion

Aspirin remains the cheapest commonly used accessible non-steroidal anti-inflammatory drug. It is also the cornerstone of antiplatelet therapy in patients with cardiovascular disorders. Salicylic acid is the active agent in the drug (aspirin), and it structurally contains benzene ring with hydroxyl (OH)- group and a carboxyl (COOH) group attached to it. The most recognized mechanism of action of aspirin is the inhibition of prostaglandin synthesis.

Cyclooxygenase enzyme is the central enzyme involved in the biosynthesis of prostaglandin. Once this enzyme is blocked by aspirin, harmful prostaglandin which mediate pain cannot be produced; hence pain is alleviated. The same case applies to the control and management of fever and inflammation reactions.

In the control of cardiovascular disease, aspirin mechanism of action involves both the inhibition of platelet activation and aggregation which blocks the generation of thromboxane A2 responsible for the antithrombotic effect.

References

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Kune GA, Kune S, Watson LF. (1998). Colorectal cancer risk, chronic illness, operations, and medications. Case-control results from Melbourne colorectal cancer study (1988) 399-404

Rao P, Knaus EE. Evolution of non-steroidal anti-inflammatory drugs (NSAIDs): Cyclooxygenase inhibition and beyond. Journal of Pharmacy and Pharmaceutical Sciences 2008:81-100

Vane JR. Inhibition of prostaglandin synthesis as a mechanism of aspirin-like drugs. Nat New Biol (1971) 232-1038

Vane JR. Inhibition of prostaglandins synthesis and mechanisms of action for aspirin-like drugs. Nature New Biology. 1971:232-245