Fluoroquinolones and Their Pharmacology, History of Use - Essay Example

Fluoroquinolones Table of Contents I. Introduction 3 II. Fluoroquinolones 4 III. Use, History and Development 7 IV. Problems, Processes for Banning or Continued Use 8 V. Conclusion 11 1References 12 I. Introduction This paper explores fluoroquinolones, their pharmacology, history of use, on-going discoveries of serious toxicological problems, and interventions to either prohibit or control their use and to mitigate the identified harmful toxicological issues, if not totally neutralize them. This discussion considers the context of the long history of new technological innovations being introduced for their touted positive benefits to human life, which later turn out to be toxic to human health or the environment, or both, in the long term (Miller 2013; Brody 2012). This exploration is being undertaken too in relation to the general toxicology of antibiotics and the dynamics of antibiotic resistance leading to human and environmental harms. Antibiotics in general have been in wide use to treat many infections, but of late have been the subject of a growing body of literature on the toxicological aspects of antibiotics, not only with regard to the toxic side effects of certain antibiotics on humans, but with regard to the growing proliferation of antibiotic waste in the environment, leading to increased levels of antibiotics in water bodies and soils. These in turn lead to adverse effects on the ecological balance of the environment, with organisms either dying or developing resistance to the antibiotics, radically changing the makeup of the environmental biomes. The adverse effects on the environment ultimately boomerang back to human beings, who suffer from the toxic effects of the antibiotics themselves, or else suffer from the environmental backlash from the proliferation of antibiotic-resistant organisms that cause new diseases and environmental problems (Klint 2012; Turner 2014; Ebert et al. 2011). Recent literature on fluoroquinolones reflects this reality, with more recent findings showing that fluoroquinolones cause long term damage to various aspects of human health, including antibiotic resistance, tendinitis, rupture of the tendons, and serious and sometimes irreversible neurological and cognitive damage, and damage to the eyes due to possible detachment of the retina, among those who take fluoroquinolones for varying lengths of time. The problem too, with fluoroquinolones, is that adverse side effects tied to neurological damage have been identified but not deemed as significant for a large portion of the population as early as the turn of the new century, and that literature on the greater risk for tendinitis and rupture of the tendons among those taking fluoroquinolones has been available since at least 2008 (US FDA 2008; CDC 2010; QVF n.d.; Mercola 2013; SMF 2011; Etminan et al. 2012). Moreover, while about 50 percent of all fluoroquinolones in the market has been taken out of it, the antibiotic is reported as continuously and widely prescribed, for conditions where the antibiotic has not been intended to be utilized at all from the early studies all the way to the approved uses of the antibiotic. The drug has been traditionally indicated for respiratory ailments and infections of the urinary tract, and has been noted to have potent activity against all kinds of organisms that cause infection, both gram positive and gram negative organisms. The most prevalent forms of fluoroquinolones meanwhile are moxifloxacin, ofloxacin, ciprofloxacin, levofloxacin, and gemifloxacin (Bloomquist 2014; Cohen 2014; Fish 2001; US National Library of Medicine 2014; Pepin et al. 2005; Wolfson and Hooper 1985; Lipsky and Baker 1999; Kamath 2013). II. Fluoroquinolones Wolfson and Hooper (1985) detail the structure and the synthesis of fluoroquinolones and their discovery from the late 1970s and early part of the 1980s as synthesized compounds of fluoroquinolones and the compounds based on quinolones that preceded them in interest, synthesis, and early consideration for use as antibiotics. Alongside such synthesis is the discovery of the potency of these compounds against a range of in vitro gram-negative organisms. Among the early compounds that have been deemed of large potential as antibiotics are ciprofloxacin, enoxacin, and norfloxacin. The successful establishment of their potency in vitro led to clinical trials with hopes of pushing out this new class of antibiotics into the mainstream, for conventional prescription and use. It is identified that the way the fluoroquinolones work in particular is through its action with the DNA gyrase, which in turn results in the inhibition of the action of the target organisms that lead to diseases in humans. Having established their efficacy to the satisfaction of the authorities, the above candidate antibiotics under this class of fluoroquinolones were further investigated and assessed for use in human beings as part of the arsenal of pharmaceuticals against specific diseases (Wolfson and Hooper 1985). The following is a partial list of organisms that were identified as target organisms where fluoroquinolones have potent inhibitory action (US National Library of Medicine 2014): penicillinase- and non-penicillinase producing Staphylococci, Streptococcus pneumoniae and viridans, Enterococcus faecalis, Listeria monocytogenes, and Nocardia species...Neisseria meningitides and gonorrhoeae, Haemophilus influenzae...Enterobacteriaceae species, Pseudomonas aeruginosa and Vibrio species (US National Library of Medicine 2014). Meanwhile, in terms of chemical structure and formula, the graphic below details the chemical structures for some specific fluoroquinolones in widespread use (Lodha 2008): Graphic Source: Lodha 2008 The early literature on fluoroquinolones has identified the conditions for which the compounds have great efficacy and power as those that are caused by the organisms listed above. As discussed earlier, these fluoroquinolones have been in wide use for a variety of infections of the respiratory tract, as well as the urinary tract in humans. Moreover, they have become widely prescribed for a host of conditions in various settings, including the war effort, even as early side effects that have been documented have been limited to liver conditions, and those have been cited as occurring very rarely. The indication from the early literature is that fluoroquinolones are generally safe for human use (Fish 2001; US National Library of Medicine 2014; Pepin et al. 2005; Wolfson and Hooper 1985; SMF 2011). III. Use, History and Development From the early literature, the uses of fluoroquinolones have become historically tied from practice to certain specific conditions, such as urinary tract infections, for which the compounds have been deemed very effective, and as having good prospects of continued use as a primary pharmaceutical intervention for patients suffering from urinary tract infections. There are several characteristics that make fluoroquinolones especially effective historically for such infections. They have high power and efficacy against the organisms that cause infection in the urinary tract. They are usually excreted through the urine, and so are able to pass through the infected areas where the organisms reside in the urinary tract, ensuring exposure and action. They have high penetrability scores for the prostate. They achieve high bioavailable levels in the human body, again ensuring action on the target organisms or pathogens. They have low interactions with other medications, making them ideal when patients have to take more than one set of medications. All these have been factors favoring fluoroquinolones have been identified in actual use. Therefore, historically, a case was made for the use of fluoroquinolones for such urinary tract infections and related conditions (Ronald and Low 2003, pp. 107-110). For other conditions, on the other hand, such as respiratory infections, fluoroquinolones have also evolved from long clinical use to likewise be viable options for use, even as these fluoroquinolones have become only secondary options for such conditions. Other drugs such as rifampicin and so-called macrolides have been deemed as more relevant first choices for respiratory ailments in general, relative to fluoroquinolones, which have taken a back seat in this regard. The short of it is that for these two conditions, and for urinary tract infections in general, the compound has become top of mind for medical practitioners for use, contributing to their widespread prescription (Root 1999, pp. 310-311; Ronald and Low 2003). IV. Problems, Processes for Banning or Continued Use Mainstream medical media and blogs, such as Dr. Mercola’s site, have added to the growing chorus of voices that point to the adverse, toxic effects of fluoroquinolones on the human body. Mercola cites for instance that the component fluoride in fluoroquinolones is a toxin for the neural system of the human body. Moreover, fluoroquinolones in general have been singled out for a range of very serious and often permanent toxic effects, leading to permanent disabilities and mortality. Two brands have been singled out for their notoriety in this regard. One is Cipro by Bayer and the other is Levaquin. The latter is said to have been the subject of lawsuits relating to its adverse health impacts on consumers. The range of adverse effects impact the nervous system, the muscular system, visual systems, and systems for urination, either in their entirety or in combinations in many cases. Among the conditions that have been tied to the use of fluoroquinolones are retinal detachment leading to vision impairment, kidney failure, depression, neuropathy on the periphery, psychosis, hearing impairment, hallucinations, brain fog, and impaired ability to metabolize sugar (Mercola 2012). Added to this are more detailed reports relating to the way the long-term use of fluoroquinolones have been documented to cause permanent damage to the nervous system, and how there is a threshold level of fluoroquinolone exposure, after which the harmful effects on health due to toxic reactions by the body suddenly appear and without warning in otherwise healthy people who are exposed to the compounds to treat chronic conditions (Mercola 2013; Bloomquist 2014). The popular media has likewise come to report on the accumulating body of evidence on the toxicity of fluoroquinolones, reinforcing some of the findings already discussed above. Some of the findings further substantiate already established harms, such as that those who take the antibiotics increase their risk of detaching their retinas by up to five times compared to the population who does not take them. Such findings in turn have prompted doctors to re-evaluate the way they prescribe this class of antibiotics for ordinary ailments with alternative, safer treatment modalities. In pneumonia, for instance, there are increasing calls from the medical community for patients to stay away from fluoroquinolones, where they have been routinely prescribed as so-called first-line drugs for treating the condition. Doctors are said to be increasingly aware of the disproportionate risks of serious side effects of these antibiotics compared to any benefit that can be had from taking them, especially in conditions other treatment options are as effective, as readily available, and not as harmful to health in other ways. Elsewhere too, the popular media has come to report how fluoroquinolones are able to attack all parts of the body and cause damage, the skin and the cardiovascular system, where the antibiotics can also cause massive and sometimes permanent damage. In the realm of the evolving resistance of pathogens to antibiotics, meanwhile, fluoroquinolones are being blamed for the increasing prevalence of MRSA and other antibiotic-resistant conditions such as those that are caused by C. difficile. In some geographies, fluoroquinolones are being blamed for more than half of new cases of conditions caused by such antibiotic-resistant pathogens. This is true, as reported in the popular press, in places such as Quebec. Fluoroquinolones are being associated likewise with some intractable or hard to treat and painful conditions such as those that result in ailments that mimic fibromyalgia in their symptoms (Brody 2012). The FDA has come up with more intense regulatory restrictions on the sale and marketing of fluoroquinolones moving forward, pressuring some makes to get out of the market altogether for instance. The FDA has also resorted to promulgating new rules requiring manufacturers to place black box warnings on the risk of tendon rupture and tendinitis from taking the antibiotics. More recently too, the FDA is reported to have strengthened warnings on the risk of neuropathy from the use of fluoroquinolones (Brody 2012; Lowes 2013). In the past, the FDA has likewise acted to tweak regulations with regard to the use of fluoroquinolones for specific conditions, and it is noteworthy that in 2007 the FDA had issued statements against the continued use of the antibiotics to treat gonorrhea, because even as early as that time the resistance levels of the organism that causes gonorrhea has reached the threshold level for continued use. As such, the 2007 statement reflects a willingness on the part of the regulatory agencies to keep track of the efficacy of fluoroquinolones versus the organisms and diseases that they were originally intended to keep in check. This particular statement reflects a long history of fluoroquinolone use being increasingly regulated in step with the development of resistance of organisms to its actions, including earlier statements that warned against the continued use of fluoroquinolones to treat gonorrhea for men who have sex with other males for the entire United States, issued as early as 2004, and earlier statements against the continued use of the same for gonorrhea acquired in Hawaii, made as early as 2000, and broadened to include gonorrhea acquired in California from 2002 onwards. Seen from this perspective, one can see that regulatory actions have kept in step with the evolution of the battle between fluoroquinolones and the organisms that they were supposed to suppress. This is on top of more recent regulations addressing the inclusion of warnings on labels for tendon rupture, tendinitis, and neuropathy as already discussed above (Brody 2012; Lowes 2013; Tucker 2007; US FDA 2013). V. Conclusion Antibiotics have had a central place among the arsenal of substances that modern medicine has made use in its fight against disease. It has had a good run, but as has become evident in the growing body of literature examined in this paper, antibiotics have had grave toxicological impacts on human beings and the environment. The casual and extensive prescription and use of antibiotics such as fluoroquinolones in particular, have been documented to cause massive harm to human physiology, cause disease-causing organisms to develop resistance, and to pollute the environment to the detriment of ecological health. Fluoroquinolones are the most recent of a queue of man-made materials that have been first touted miraculous in its various effects, but have been later found to be toxic in other ways, negating even their purported benefits. 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