Ibuprofen Ert

Chronic inflammatory pain and disease are major worldwide health problems, which are responsible for three in five deaths, and has contributed to the global opioid epidemic (Pahwa & Jialal, 2018). Nonsteroidal anti-inflammatory drugs (NSAIDs), and in particular, Ibuprofen, are among the most frequently consumed drugs available for non-addictive treatment of mild inflammatory pain (Grosser, Ricciotti, & FitzGerald, 2017). NSAIDs generally have both analgesic and anti-inflammatory effects, making them particularly useful for the treatment of pain. Sometimes referred to as non-opioid analgesics, these drugs denote a divergent group of chemical compounds of which their mechanism of action generally implicates the inhibition of components of the inflammatory response system (Hersh & Dionne, 1998). Preceding the discovery of ibuprofen, inadequate analgesic NSAID drugs were available. Aspirin was relied on for treatment; however, gastric irritation at doses high enough to control symptoms limited the drug’s usefulness. Consequently, ibuprofen was industrialised directly subsequent to complications associated with the conventional NSAIDs at the time.

Readily accepted, the medication’s therapeutic efficacy was considered to compensate for the severity of its side effects (Busson, 1986). Ibuprofen was the first single-entity oral analgesic permitted by the FDA that showed greater or similar potency to that of aspirin. Discovered in the United Kingdom in the 1960s from a derivation of propionic acid in an attempt to find a safer alternative to aspirin to relieve symptoms of inflammatory pain, the medicine has numerous advantages over drugs designed to have similar effects in the human body such as paracetamol, its original: aspirin, and the opioid codeine. Despite their similarities, Ibuprofen is justifiably a drug of higher significance in everyday life due to the chemical structure of the drug known as RS-2-4-Isobutylphenyl propanoic acid, its low toxicity and limited side effects in comparison, and the environmentally friendly production process (National Center for Biotechnology Information, 2018).

Argument 1: Structure, Functional Groups, How Effects Mechanism of Action

Belonging to the class of organic complexes known as phenylpropanoic acids and molecular ring affixed to a propanoic acid, ibuprofen is comprised of a carboxylic acid functional group and alkane substituents (Purdue University, 2018). Essential to both the analgesic and anti-inflammation qualities the medicine possesses, the focal mechanism of action is the non-selective, reversible inhibition of the cyclooxygenase I and II, of which are enzymes concerned with prostaglandin synthesis, similarly to other NSAIDs, aspirin and acetaminophen (Bushra & Aslam, 2010). This subsequently blocks the group of fatty acid molecules, or lipids that are made at the site of tissue damage or infection, processing and releasing responses of inflammation, blood flow and the formation of blood clots (Ophardt, 2003). Of its properties, the optical activity of ibuprofen is thought to be particularly interesting. With the ability to exist as a pair of optical isomers that are non-superimposable mirror images of each other, the two isomers are identified as the R-enantiomer and S+Enantiomer. The medicine is administered as a racemic mixture, because of its single stereocentre, meaning it is a compound that has equal amounts on the left and right enantiomer of the chiral molecule. Through this, the R-ibuprofen endures extensive conversion to the S+ibuprofen in vivo in attempts to minimise side effects (Chen, et al., 1991). The isomers are identical in the properties of solubility and melting and boiling point; however, the S-enantiomer is the more pharmacologically active enantiomer due to its behaviour when interacting with prostaglandins. They are distinguished by their rotation of the plane of polarisation of polarised light in different directions: the S isomer rotates clockwise as the subject looks at the light, in comparison to the anticlockwise R isomer anticlockwise (Royal Society of Chemistry, 2007). Prior to the development of ibuprofen and further development of technology in the 1990s, there was suspicion, yet no empirical evidence of a second or third COX enzyme. Both ibuprofen and its original, aspirin, inhibit both COX I and II; but through different bonding. Ibuprofen binds non-covalently to the enzymes, thus competing with the enzyme’s natural counterpart, otherwise referred to as reversible inhibition. Conversely, aspirin forms covalent bonds to the serine residue in the enzyme, a bond which is unable to be broken, making it irreversible inhibition. This creates major issues in the context of side effects such as stomach ulcers and internal bleeding with aspirin, and thus the reasoning behind the wider use of ibuprofen. However, the new-found selective targeting of COX enzymes has created a challenge for a development of drugs that interact pharmacologically with specific enzymes and bonds (Autret, et al., 1997).

Argument 2: Side Effects & Toxicity

The abuse and misuse associated with painkillers and medicines of all kinds is one of the major issues facing society today. While there is no safe level of drug use due to the associated risks and unwanted side effects, ibuprofen is most certainly the preferred NSAID, and anti-inflammatory analgesic in general, based on its advantageous gastrointestinal and nephrotoxicity characteristics (Ungprasert, et al., 2012). Though the selection of the most appropriate kind of medicine for each patient is tailored to their medical background and the choice of a medical professional, ibuprofen is the least ulcerogenic NSAID. With multiple modes of action underlying the behaviour of the drug’s agents, the pharmacokinetics are linked with the toxicological and pharmacological effects. The rapid oral absorption of the two isomers leads to accumulation of the enantiomers in inflamed pathways and sites (Rainsford, 2015). Despite the lessened gastrointestinal irritation from aspirin, the competition between the R- and S+ isomers with active sites on the COX-1 enzyme may explain the still viable, but low ulcerogenicity. The significant inhibitory effect on leucocytes, or more commonly known white blood cells, affects their accumulation and activation at inflamed sites. However, of the relevant drugs available, the chronic gastrointestinal ulceration and effect of leucocytes are perceptibly lower than some more potent ulcerogens such as aspirin and naproxen, as according to data from a human study conducted by Cardoe in 1975 (Rainsford, 2015).

In terms of toxicity, the first fourteen years of ibuprofen’s availability as a prescription-only anti-inflammatory drug was rarely reported to have been taken in overdosage. However, once the drug was released as an over the counter analgesic, the prediction that it would consequent in more frequent overdoses. Not only was abundant evidence provided of this, and that analgesics, including ibuprofen, were most frequently encountered in an overdose, epidemiological evidence arose that in the United Kingdom, 50-76% of self-poisonings were of this type of drug (Rainsford, 2015). A statement from a July 1999 issue of the American Journal of Medicine stated that “approximately 107,000 patients are hospitalised annually for NSAID-related complications… at least 16,500 NSAID-related deaths occur each year among arthritis patients alone” (American Nutrition Association, 1999). The management of analgesic overdoses denotes a major healthcare issue, particularly with those of opioid-based medicines. These medications primarily generate a psychological addiction, in addition to the extent of their efficacy in comparison to an NSAID, such as ibuprofen, for the treatment of chronic pain not having been empirically proven. Likewise, common side effects of opioid administration include respiratory depression, nausea, physical dependence and addiction (Benyamin, et al., 2008). In contrast to these drugs, in addition to aspirin and paracetamol, ibuprofen does not seem to display an additional pathophysiological mechanism in overdose. Thus, any toxic effects are thought to be related to the inhibition of prostaglandin synthesis.

Argument 3: Packaging & Production

Finally, since the introduction of ibuprofen by the Boots Group, the drug has become one of the most common painkillers to date. Like other drugs of its class, it possesses analgesic, antipyretic and anti-inflammatory properties. However, though being a simple molecule, there is a structural complexity to the production of ibuprofen. Boots’ original method of the production of ibuprofen separated the compound 2-methylpropylbenzene from crude oil; producing a comparable frame to the structure of ibuprofen. Once the patent ran out in the mid-80s, a new company formed with a mission to develop a ‘green’ synthesis of ibuprofen. Developed in just three steps, with only acetic acid as a bi-product, the synthesis developed a greater atom economy; meaning the efficiency of chemical conversion from their singular forms, in terms of all atoms involved and the desired products produced became of better condition in regards to the proficiency and environmental impact of production (Royal Society of Chemistry, 2014). Overall, it can be seen that the steps taken to ensure the safety of the planet and those manufacturing the medicine has improved, making it not only a significant drug, but superior to others that aim to achieve the same or larger pain and inflammation alleviation, such as the use of opioids. This class of drugs are naturally found in the opium poppy in Southern Asia. While some prescriptions are made directly from the plant, others are made through the scientific development of an extremely similar chemical structure by adding specific chemicals to morphine (National Institute on Drug Abuse, 2018). A particular example of this is oxycodone, produced by pharmaceutical companies by adding hydrochloride (Alcohol and Drug Foundation, 2017).

Accumulatively, the analgesic, anti-inflammatory and antipyretic effects of ibuprofen are highly superior to alternatives such as opioids and paracetamol, of which aim to have similar medical effects. However, despite these similarities, ibuprofen has exceeded the qualities of other drugs since its discovery in the 1960s. The drugs’ focus on blocking the mechanism of prostaglandin through the non-selective reversible inhibition of cyclooxygenase I and II attributes to its effectiveness. Its non-covalent bond with the enzymes and administration as a racemic mixture due to its structure and chiral molecule lessens side effects inclusive of gastrointestinal complications and internal bleeding. Although still negative, in comparing ibuprofen to the high addiction rates of opioids and the high ulcerginicity of the original formula of aspirin, ibuprofen has far fewer side effects and lessened toxicity. Finally, the innovation and evolution of the production process of ibuprofen has a large effect on society through minimal environmental impacts. Ibuprofen in certainly the more superior drug in regards to pain relief and anti-inflammatory aspects based upon analysed evidence, it is recommended that ibuprofen be the first-choice analgesic rather than inferior and addictive products.