Talk:Quinolone

cleanup

I put a cleanup tag on this because it seems a bit all over the place. Compare with other antibiotic class articles. The adverse effects section could be a little more succinct, and a picture of the quinolone core ring system would be good. ben 14:04, 23 June 2006 (UTC)

This page [1] looks like it has some good source material for references...notes on the differences between the various generations would be good...too tired to go through it now...ben

The adverse reactions sections needs an update; as time goes on, I believe there are many more cases of tendon rupture complications than this article would indicate. The tendon ruptures either were not connected to the drug, or they have not been properly reported. Mare —Preceding unsigned comment added by 209.244.4.106 (talk) 17:01, 28 January 2008 (UTC)

ProQuin XR does not appear

ProQuin XR (Esprit Pharma) is a prolonged release ciprofloxacin, but it doesn't appear in this article. It is NOT equivalent to Cipro XR (Bayer Healthcare), which contains two forms of ciprofloxacin (see below).

ProQuin XR is actually pretty neat, expanding in the stomach over a number of hours.

From the ProQuin XR PI (http://www.proquinxr.com/pi/proquinxrpifull.pdf): "ProQuin XR (ciprofloxacin hydrochloride) extended-release tablets contain ciprofloxacin hydrochloride"

From the Cipro XR PI (http://www.ciproxr.com/HCP/pi.asp)  : "The tablets contain a combination of two types of ciprofloxacin drug substance, ciprofloxacin hydrochloride and ciprofloxacin betaine (base)."

insertion by Ananyo u

The following was inserted in the article on 10:59, 18 July 2006 by User:Ananyo u. I moved it here, because it was placed between the interwikilinks. May it's useful and should be inserted correctly in the article. Greetings --Saibo (Δ) 22:20, 18 July 2006 (UTC)

norfloxacin in combination with tinidazole or metronidazole is frequently used in veterinary medicine, specially in mixed enteric infection with bacteria and protozoa. the generic names are Normet susupension(norfloxacin with metronidazole), TiniNF suspension(tinidazole with norfloxacin)etc.

Resistance

I pulled the following text from the article:

Because of this serious problem the quinolones are generally not considered a first line agent but rather a drug of resort when therapy with other classes of antibiotics has failed or is inappropriate. It is hoped that judicious use of quinolone drugs may prolong the useful life of this group.

Jim Hoover, regional manager for state government affairs for the Bayer Corporation for the five northwest States, discussed the second and third generation quinolones. He states that "...Normally the quinolone class of drugs is used in patients who have failed at least one prior therapy. The patients tend to be fairly ill and require relatively acute care that often may be the last step before they are admitted into the hospital. …By the time the physicians get to this classification, they tend to have a good idea of what bacteria is involved, what antibiotic is the most potent for the bacteria and which penetrates that particular body side the best. …These drugs are often the last step before admission into the hospital..."

Perhaps this is true in some parts of the world but FQs are very much the first-line agent in the United States, particularly in the emergency rooms (broad coverage and good bioavailability make it a "no thinking required" antibiotic). IDSA recommends it as a first-line agent for UTIs when TMP/SMX resistance is over 20% and treatment failure due to use of second-line agents cannot be tolerated, and levofloxacin has been approved for CAP. And let's not quote drug company spokespeople -- very little truth comes out of their mouths. - Emt147 ^Burninate! 05:36, 11 October 2006 (UTC)

Fact adjustments

A few notes:

1) Bacillus anthracis is not intracellular. If it were, it would not be susceptible to beta-lactam antibiotics (e.g., penicillin). A fluoroquinolone (ciprofloxacin) is an effective treatment for anthrax, however. It is the preferred means of treating inhalational anthrax.

Please note that this is no longer the case. The CDC has withdrawn it's endorsement of Ciprofloxacin to treat Anthrax due to it's horrendous safety profile. Doxycycline remains the first line agent for this disease state.Davidtfull (talk) 09:40, 24 January 2009 (UTC)

2) Other intracellular bacteria include Mycoplasma pneumoniae and chlamydiae.

3) Peripheral neuropathy is not necessarily irreversible in quinolone exposure.

4) Rhabdomyolysis is not muscle wasting in the common sense of the term. Significant rhabdomyolysis most often occurs without evident wasting of the muscle.

5) Widespread use of fluoroquinolones in the developing world, particularly a population's unrestricted access to antibiotics, is also implicated in the rise of fluoroquinolone resistance.

I changed the text to fit these notes where it seemed appropriate.Dyslexic3 03:58, 6 December 2006 (UTC)

Additional fact adjustments that need to be made:

Several of these agents that are listed in this article have either been withdrawn from the market, or have been discontinued because of adverse effects, but are not noted as such. For example:

Clinafloxacin is listed as being in the experimental stage even though it had been discontinued nine years ago because of phototoxicity and hypoglycaemia. November 1999 Development was discontinued due to severe phototoxicity and glucose homeostasis See: http://www.chemdrug.com/databases/8_0_pnmripllpnoqnkpv.html See: http://www.courses.ahc.umn.edu/pharmacy/6124/handouts/Fluoroquinolones.pdf

Sparfloxacin is listed with no notations even though it has been withdrawn because of phototoxicity See: http://www.drugs.com/mtm/sparfloxacin.html

Gatifloxacin (Tequin) is listed with no notations even though it is no longer manufactured by Bristol-Meyers Squibb, May 2006 due to severe adverse reactions.

Tosufloxacin is listed with no notations even though it has been withdrawn due to causing severe thrombocytopenia and nephritis.

Sitafloxacin is listed with no notations even though it too has been withdrawn. “Some of promising antibiotics of this group were withdrawn because of serious adverse reactions (sparfloxacin, trovafloxacin, grepafloxacin, clinafloxacin, sitafloxacin).”

See: http://old.lf3.cuni.cz/studium/materialy/infekce/en_atb.doc

See: A critical review of the fluoroquinolones: Focus on respiratory tract infections ZHANEL George G. ; ENNIS Kelly ; VERCAIGNE Lavern ; WALKTY Andrew  ; GIN Alfred S. ; EMBIL John ; SMITH Heather ; HOBAN Daryl J.

See: History of Quinolones and Their Side Effects Ethan Rubinstein Department of Internal Medicine and Unit of Infectious Diseases, Tel Aviv University School of Medicine, Tel Aviv, Israel Chemotherapy 2001;47:3-8 (DOI: 10.1159/000057838)

Additionally: Penetrex enoxacin 200mg tablet; oral is listed as Discontinued on the FDA site. Penetrex enoxacin 400mg tablet; oral is listed as Discontinued on the FDA site. Cinobac cinoxacin 250mg capsule; oral is listed as Discontinued on the FDA site. Cinobac cinoxacin 500mg capsule; oral is listed as Discontinued on the FDA site.

See: http://www.accessdata.fda.gov/scripts/cder/drugsatfda/

In regards to Flumequine (veterinary use), : Several FDA/CVM scientists participated in the 60th Meeting of the Joint FAO/WHO Committee on Food Additives (JECFA) held in Geneva, Switzerland, February 6-12, 2003. JECFA was convened to evaluate certain veterinary drug residues in food. At the 60th meeting, the Committee recommended new MRLs for neomycin in cattle liver, kidney and milk; for imidocarb in cattle muscle, liver, kidney, fat and milk and dicyclanil in sheep muscle, liver, kidney, and fat. In addition, the Committee recommended that the ADI for trichlorfon be lowered from 20 to 2 ug/kg bw per day. The Committee withdrew the MRLs for flumequine and carbadox based on evidence showing both are direct acting genotoxic carcinogens and, therefore the Committee was unable to establish an ADI for human exposure to residues. 96.254.65.104 (talk) 01:06, 9 December 2008 (UTC)

Generations of fluoroquinolones

According to the AAFP, gatifloxacin is 4th generation, not 3rd as suggested. Also the trade name Zymar refers to the ophthalmic solution and not to the po or iv. —The preceding unsigned comment was added by Sedmic (talk • contribs) 06:42, 15 January 2007 (UTC).

Please see http://www.aafp.org/afp/991201ap/tips/3.html . Ramin Herati (Sedmic) 06:42, 15 January 2007 (UTC)

The reference provided by Ramin is over ten years old and no longer relevant. The classifications of the fluoroquinolones vary widely amongst various authors. Some classify them by structural changes, where as others classify them by patent date, and yet a third classify them by decades. There really is not a correct way of classifying the generations of quinolones. Generally those drugs that have not been modified by the addition of the fluorine atom are to be considered quinolones and those who do have this modification are to be considered fluoroquinolones. As such it is generally accepted that any drug manufactured prior to Norfloxacin are to be considered first generation quinolones (prior to 1978), those manufactured between 1978-1980 second generation, between 1980-1990 third generation, between 1990 to date fourth generation. But this is far from being a hard and fast rule as there have been hundreds if not thousands of drugs manufactured worldwide that are to be considered quinolone/fluoroquinolone drugs. More than ten thousand analogs have been synthesized from nalidixic acid alone though only a handful ever made it to market.

1934 Chloroquine
1958 7- Chloroquinolone
1962 Nalidixic Acid Belgium Patent Sterling Drugs
1967 Oxolinic Acid (quinoleine) German Patent Warner/Lambert
1974 Pipemidic Acid (pyrido-2-3-pyrimidine) German Patent Roger Bellon
1973 Rosoxacin
1973 Flumequine (benzo quinolizine) German Patent Rikker Labs
1978 Norfloxacin (6-fluoro-7-pyrididino-quinoleine) Belgium Patent Kyorin
1979 Pefloxacin German Patent Roger Bellon/Dainippon
1982 Ofloxacin European Patent Daiichi
1983 Ciprofloxacin German Patent Bayer AG
1985 Sparfloxacin Daiichippon
1987 Levofloxacin European Patent Daiichi
1987 Clinafloxacin Kyorin
1988 Temafloxacin Toyama
1988 Gatifloxacin Kyorin
1989 Grepafloxacin Otskuda
1993 Trovafloxacin Pfizer
1994 Moxifloxacin Bayer AG
1994 Gemifloxacin LG Chemicals LTD Korea

Withdrawn, discontinued or restricted:

Moxifloxacin restricted in Europe due to toxicity issues
Norfloxacin restricted in Europe due to lack of efficacy
Cinoxacin discontinued
Gatifloxacin removed due to toxicity issues
Enoxacin removed due to toxicity issues
Grepafloxacin removed due to toxicity issues
Sparfloxacin removed due to toxicity issues
Temafloxacin removed due to toxicity issues
Trovafloxacin removed due to toxicity issues
Davidtfull (talk) 14:41, 26 January 2009 (UTC)

topoisomerase 4 and 2

topo 2 is what humans have. topo 4 is what bacteria have. fluoroquinolones can affect both, but mainly topo 4- the target of interest. if these drugs greatly affected topo 2 we would be in trouble (there are drugs, like anthracyclines, targeting topo 2 and they are antineoplastic). for some reason i have noticed people editing the article to make topo 2 a target along with dna gyrase. this is incorrect. quinolones work by affecting mainly topo 4 (gram positive bacteria target) and dna gyrase (gram neg target). Brendan19 08:43, 14 May 2007 (UTC)

With all due respect I beg to differ with Brendan's opinons regarding this. Fluoroquinolones, which perform their bactericidal effect by inhibiting DNA gyrase (a type II topoisomerase), are known to interfere with certain immune functions. Ciprofloxacin and other quinolones at >20 µg/ml inhibit peripheral blood lymphocyte (PBL) cell growth by 30 to 35%, causing impaired cell cycle progression through the S phase. (see Castora, F. J., F. F. Vissering, and M. V. Simpson. 1983. The effect of bacterial DNA gyrase inhibitors on DNA synthesis in mammalian mitochondria. Biochim. Biophys. Acta 740:417- 427.) Cell cycle analysis thus indicates DNA synthesis to be inhibited by fluoroquinolones at these concentrations. The fluoroquinolones interfere with DNA replication by inhibiting an enzyme complex called DNA gyrase. But this also affects mammalian cell replication. Quinolones are highly toxic to mammalian cells in culture. Recent studies have demonstrated a correlation between mammalian cell cytotoxicity of the quinolones and the induction of micronuclei. For example trovafloxacin inhibited bacterial topoisomerase and mammalian topoisomerase II (which is essential for transcription by RNA polymerase II). Gene expression changes caused by trovafloxacin were compared to that caused by the topoisomerase II inhibitor, etoposide and similar downregulation of genes involved in RNA transcription was observed with both drugs. (see Hepatology Highlights (p 227-228) Neil Kaplowitz Published Online: 18 Jan 2005 DOI: 10.1002/hep.20596)

In another example after exposure to 10 and 30 mg Bay y 3118, a dose-dependent induction of damage to the mtDNA has also been reported. (see Damage to mitochondrial DNA induced by the quinolone Bay y 3118 in embryonic turkey liver.)

McQueen and Williams (36) found that norfloxacin, ofloxacin, pefloxacin, and ciprofloxacin induced DNA breakage and repair in the in vitro rat hepatocyte assay at levels between 300 and 500 p,g/ml. (see McQueen, C. A., and G. M. Williams. 1987. Effects of quinolone antibiotics in tests for genotoxicity. Am. J. Med. 82(Suppl. 4A):94-96.)

CP-67,015, a quinolone under investigation, was shown to induce chromosome aberrations in cultured human lymphocytes at levels of .50 ,ug/ml and produced genetically abnormal bone marrow cells in mice given five daily parenteral doses of 500 mg/kg per day. Furthermore, CP-67,015 was found to be at least 10-fold more potent than nalidixic acid, norfloxacin, oxolinic acid, or ciprofloxacin at enhancing eucaryotic topoisomerase IImediated DNA cleavage in vitro (see J. J. Barrett, T. D. Gootz, C. A. Farrell, S. A. Sokolowski, and M. Frescura, Program Abstr. 27th Intersci. Conf. Antimicrob. Agents Chemother., abstr. no. 249, 1987 and Holden, H. E., J. F. Barrett, C. M. Huntington, P. A. Muehlbauer, and M. G. Wahrenburg. 1989. Genetic profile of a nalidixic acid analog: a model for the mechanism of sister chromatid exchange induction. Environ. Mol. Mutagen. 13: 238-252.).

CP-67,015 is a 4-quinolone that is inhibitory to both procaryotic and eucaryotic type II topoisomerases and clearly induces genotoxic changes in standard in vitro and in vivo tests at drug levels that approach physiological relevance.

A number of positive in vitro genotoxicity test results have been documented with several different 4- quinolones, the effective concentrations would be clinically achieved predominantly in the urinary tract (see Bergan, T. 1988. Pharmacokinetics of fluorinated quinolones, p. 119-154. In V. T. Andriole (ed.), The quinolones. Academic Press, Inc., New York and Bergan, T., and A. Dalhoff. 1986. A review of the pharmacokinetics and tissue penetration of ciprofloxacin, p. 23-36. In H. C. Neu and H. Wenta (ed.), Proceedings of the First International Ciprofloxacin Workshop. Elsevier Science Publishing, Inc., Amsterdam.)

Fluoroquinolones are potent inhibitors of bacterial topoisomerase II (DNA gyrase). They also inhibit eukaryotic topoisomerases, which could possibly lead to clastogenicity and/or cellular toxicity. Recent studies have demonstrated a correlation between mammalian cell cytotoxicity of the fluoroquinolones and the potential of these compounds to induce micronuclei, a genetic toxicity endpoint. (see Fluoroquinolones: relationships between structural variations, mammalian cell cytotoxicity, and antimicrobial activity. Suto MJ, Domagala JM, Roland GE, Mailloux GB, Cohen MA.)

As such it would be correct and factual to state that these drugs may cause DNA damage to human cells. As Brendan had stated that if this were to be the case “we would be in trouble”, actually the fact of the matter is that indeed we are indeed in serious trouble concerning this class. All one has to do is review the safety profile of this class, and the literature that describes the mechanism of action by which such reactions take place, should they require additional proof.96.254.65.104 (talk) 20:30, 7 December 2008 (UTC)

External links

External links on Wikipedia are supposed to be "encyclopedic in nature" and useful to a worldwide audience. Please read the external links policy (and perhaps the specific rules for medicine-related articles) before adding more external links.

The following kinds of links are inappropriate:

• Online discussion groups or chat forums
• Personal webpages and blogs
• Multiple links to the same website
• Fundraising events or groups
• Websites that are recruiting for clinical trials
• Websites that are selling things (e.g., books or memberships)

I realize that some links are helpful to certain users, but they still do not comply with Wikipedia policy, and therefore must not be included in the article. WhatamIdoing (talk) 07:11, 17 January 2008 (UTC)

which are fluoroquinolones ?

The table at the bottom implies all but the first generation of quinolones are fluoroquinolones. The side effects and concern about fluroquinolones is so great that it would be useful to say something about the non fluorinated quinolnes. Sadly fluoroquinolone just redirects to this article. Rod57 (talk) 13:01, 9 September 2008 (UTC)

I agree that the side effects of fluoroquinolones are of major concern. A neighbour of mine took them in combination with corticosteroids and they destroyed literally his tendons in his feet. He used to be a triathlete. Now he has trouble walking years later. I know someone else who got extreme anxiety and insomnia from taking fluoroquinolones. I think quinolones have some pretty nasty side effects to but whether the fluorination of quinolone molecule significantly enhances the toxicity of the quinolone molecule would require some extensive research of the medical literature. I am not sure if it is particularly relevant though and worth the effort of researching the old first generation quinolones because they are not used very much in medicine anymore, partly because the newer ones have better sensitivity against a wider range of bacterium and partly due to marketing by the drug companies of patented new antibiotics. I think that the fluoroquinolone articles require some development surrounding the potentially serious and long lasting and sometimes permanent side effects of this class of drug but I don't have the time to do it. I added a couple of references to the main fluoroquinolone article and added some info on drugs which enhance the toxicity of fluoroquinolones eg corticosteroids and NSAIDs a few days ago.--Literaturegeek | T@1k? 21:30, 10 September 2008 (UTC)

Extensive research of the literature had been done by the Fluoroquinolone Toxicity Research Foundation and it was found that whether or not the drug(s) were fluorinated had little to nothing to do with the severity of the reactions experienced by the patients. The non fluorinated quinolones had the same severe reactions associated with their use as the fluorinated class. i.e. tendon ruptures, liver toxicity, peripheral nueropathy, ect. However some structural changes of the quinolone ring are associated with an increase incident of a specific adverse reaction.

It has been shown that the radical in position 5 of the fluoroquinolone ring is responsible for QTc prolongation. The methyl group at position 5 is associated with the prolongation of the QTc interval found with Sparfloxcacin. An amino group at position 5 is associated with the prolongation of the QTc interval found with Grepafloxacin. A proton (H) at this position is associated with the QTc prolongation found with Ciprofloxacin, Gatifloxacin, Gemifloxacin, Moxifloxacin and Levofloxacin.

The phototoxic potentials of fluoroquinolones are influenced not only by the substituent at position 8 (Halogenation at position C8) but also by those at position 1. Drugs such as Lomefloxacin and Sparfloxcacin, with a C8-fluorine substituent, and Clinafloxacin, with a C8-chlorine substituent, exhibit a greater incidence of phototoxic reactions than drugs without this substituent. However, severe rashes are class effects of the fluoroquinolones due to hypersensitivity, regardless of any structural modifications of the drug.

Nothing has been documented that would show that the addition of the fluorine atom has anything to do with the safety profile of this class. All the evidence points to the inherent toxicity of the quinolone ring itself being responsible, with the exceptions noted above.96.254.65.104 (talk) 19:49, 7 December 2008 (UTC)

Fair enough, but rather than getting too deep into the technicalities of the toxicities which is way beyond 99.9% of readers of the articles, what I recommend doing is citing credible sources, such as peer reviewed articles in the quinolone articles. Doing so will mean that doctors, pharmacists and especially patients who google their medication will be able to find an accurate list and explaination of the side effects, their severity and their duration. This quinolone article documents many of the side effects and toxicities but other articles on the individual quinolones are very much lacking in data concerning side effects and toxicity. If you feel that this or other articles on quinolones is lacking in certain areas please do get involved and help to develop the quinolone articles. The Fluoroquinolone Toxicity Research Foundation, seems to reference quite heavily credible peer reviewed articles, why not use some of these as citations?--Literaturegeek | T@1k? 01:35, 22 January 2009 (UTC)

If you have reliable sources it may be useful to cover the mechanisms of toxicity in this new article Fluoroquinolone toxicity syndrome, but it is too indepth for the quinolone article in my opinion.--Literaturegeek | T@1k? 03:15, 22 January 2009 (UTC)

Literaturegeek: I (96.254.65.104) am the director of the Fluoroquinolone Toxicity Research Foundation and indeed you will find well over 4000 credible peer reviewed articles on our site that document the horrendous safety profile of this class as well as the known mechanism of action, that go back over four decades. The problem is that the documentation is so extensive (literally thousands of webpages on our site alone) I have no clue how to even begin to cite to this massive amount of information. My previous involvement resulted in just about everything I contributed being deleted. As such I am hesitant to put so much effort into these articles only to have someone delete whatever I may add within days of my doing so. Perhaps it would be best that I simply post my suggestions on the discussion pages and have someone with more experience edit them to comply with Wikipedia's standards. I recently joined Wikipedia to try and help with this project, but it is quite frustrating to provide extensive documentation only to find that it is promptly deleted by others as it fails to comply with the drug companies propaganda that these drugs are "safe and effective antibiotics with minimum side effects".Davidtfull (talk) 09:35, 24 January 2009 (UTC)

If you prefer to post your suggestions on talk pages that is fine. Everyone was new to wikipedia once and made mistakes early in their editing "career". With time you learn how wikipedia works. Wikipedia doesn't work on a drug company agenda, (unless an article gets hijacked by drug companies). It may have been how you worded the text eg like a disclaimer rather than keeping it in encyclopedic factual tone. Content if it is referenced and verifiable from credible sources, preferably peer reviewed, it shouldn't be deleted. Sometimes data which one person may regard as propaganda gets added to wikipedia but if you can find a source which disagrees with one set of statistics, you can cite it and say,,,,, However, these reults are disputed by a study conducted, blah blah. This is how wikipedia works by allowing both sides if credibly verifiable to be cited. This is how wikipedia is neutral or tries to be. If you feel edits which are unfairly removed through vandalism either by some teenager or a drug company, reverse the edits and if necessary raise the issue on the talk page.--Literaturegeek | T@1k? 21:40, 24 January 2009 (UTC)

I have reconsidered my views regarding this article having failed to realize that the massive display of the quinolone generations was part of the reference section and not the article itself. (This should be removed and substituted with a link instead) As such I have deleted my previous comments which would have been unfair criticism. However I do think we should consider removing the pictures of the chemical structures as well as correct the number of factual errors found on that page. As well as add the considerable amount of relevant data that is missing at the moment. My apologies to anyone I may have offended by unfairly critiquing this page.Davidtfull (talk) 23:50, 26 January 2009 (UTC)

External links (2)

I see that there is some adding and reverting of external links. Would it be better if we linked to Dmoz for neutrality? Or just add it to the fluroquinolone toxicity article? I am not totally familar with external links policies.

• {{DMOZ|Society/Issues/Health/Drugs/Medical}}

or another one (scroll down)

• {{DMOZ|Health/Pharmacy/Drugs_and_Medications/Antibiotics/}}

--Literaturegeek | T@1k? 19:01, 16 February 2009 (UTC)

DMOZ is always an option. WP:ELNO is quite strict, especially the first criterion. See also Talk:Quinolone#External links above for some sites which aren't eligible for inclusion. --Steven Fruitsmaak (Reply) 19:18, 16 February 2009 (UTC)

The sites aren't discussion forums or blogs but one of the sites is a personal website of one of Mr Fuller I believe. I could add it as an "independent" editor. The first DMOZ link only has two websites one of which deals with quinolone toxicity, maybe it would be ok to add to the fluoroquinolone toxicity page. The 2nd DMOZ link is a lot more broad giving lots of different antibiotic websites and therefore may be more appropriate for addition to this quinolone page? DMOZ link 1 add to fluoroquinolone toxicity, DMOZ link 2 add to this quinolone article. What do you think of this idea?--Literaturegeek | T@1k? 19:41, 16 February 2009 (UTC)

invalid link

link [20] tagged as invalid. Perhaps the author was referring to this statement, found within the article: "Rare adverse effects attributed to some members of the quinolone family (e.g., Torsades de Pointes, hepatotoxicity, and dysglycemias) are more likely to occur in select "susceptible" populations. " And attributed "susceptible" to mean the elderly. As ref [12] makes reference to the elderly too. I believe the error here is not the two citations used. But rather thier placement. However this is not clear as the context is referring to overdose. Overdose is more than likely to take place in children and the elderly I would think. So it may not be the references but the way the sentence is structured when using them. Either way it needs fixing.Davidtfull (talk) 18:47, 21 February 2009 (UTC)

I reworded it and fixed the reference. Is it more clear now? I cut some material from the fluoroquinolone toxicity article and added it to this article, so I might have messed up the references and the context because of that.--Literaturegeek | T@1k? 20:11, 21 February 2009 (UTC)

POV check

I've nominated this article to be checked for its neutrality. After reading through it, I find the section "Scripting Abuse and Bacterial Resistance" to be extremely concerning. The POV being pushed appears to be that quinolones are dangerous and of limited use and should be avoided at all costs. However, even if true, the fact remains that this is a highly prescribed drug, and if what the article claims were as blatantly obvious as it indicates, one would imagine things would have changed. Any other thoughts? —/Mendaliv/^2¢/_Δ's/ 06:02, 22 February 2009 (UTC)

I have viewed the article and I agree that some of the recent additions to the article violated neutrality. There was also a lot of uncited data which even if true seemed to have an unencylopedic tone of the editor who added it. I have removed a lot of this data. I think I have removed the parts of most concern in the scripting abuse section. I do however, think that the remaining data is largely accurate. For example there is a lot of scripting abuse. However, this is not entirely the doctors fault because many patients will demand antibiotics for simple head colds and virus's rather than genuine infections. There is a problem with antibiotic resistance from scripting abuse/overuse. There are however, toxicity issues with the quinolones in a minority of users which are quite notable in that they can cause prolonged disabilty, peripheral neuropathy, CNS toxicity, tendon damage, muscle and joint symptoms etc etc. I think that there was also an undue weight to the article. I believe that I have resolved the worst of the POV issues and the blatant neutrality violations now.--Literaturegeek | T@1k? 09:31, 24 February 2009 (UTC)

I have removed the tags added for now. There probably are some remaining POV issues but I think they are relatively minor compared to before I removed the worst of the data you were complaining about. I don't think that there is any need fro urgent review after my deletions. There is quite a lot of work being done to a number of quinolone articles and I am sure that the quinolone article will be further reviewed and improved in the coming weeks or months.--Literaturegeek | T@1k? 09:35, 24 February 2009 (UTC)

Awesome! Thanks for taking a look at this. It looks a lot better now. —/Mendaliv/^2¢/_Δ's/ 20:21, 27 February 2009 (UTC)

I have significant concerns about the validity and neutrality of the paragraphs under the Mechanism heading. The last two sentences of the first paragraph contribute nothing to the mechanism action of quinolones as antibacterial agents, are highly subjective in nature and are just very poorly written. To cite the most frightening example, implying that chloramphenicol is not toxic to eukaryotes is plain wrong (Goodman & Gilman's The Pharmacological Basis of Therapeutics, 11th Edition has a very nice section on chloramphenicol toxicity). I would recommend that these sentences be removed and the subsequent paragraph be merged with the first sentence of the first paragraph. In reference to the second paragraphy, I believe we can safely say with a high amount of certainly that Eukaryotic cells do not contain DNA gyrase or topoisomerase IV, though we do have topoisomerases such as eukaryotic topoisomerase II. The second to last sentence is awkwardly written. Certainly, the mechanism of toxicity to humans, thus explaining adverse reactions and side effects, has yet to be fully defined. It is grossly apparent that this article has been under significant pressure from biased and non-scientific contributors. I take issue with this because I refer patients to Wikipedia, among other patient education sources. After reading the discussion posts, appears you have done considerable repair to the article thus far. Keep up the good work. --Kitstermd (talk) 20:25, 14 March 2009 (UTC)

I believe that the last two sentences that you are objecting to do contribute to understanding the mechanisms employed by this class. Altering DNA is a rather unique method of eradication that is not fully understood. Hence is does carry a certain risk that is not fully understood or perhaps even recognized.

The first sentence comes directly from Harper's Illustrated Biochemistry By Robert K. Murray, Darryl K. Granner, Peter A. Mayes, Victor W. Rodwell Edition: 27, illustrated, revised Published by McGraw-Hill Professional, 2006 ISBN 0071461973, 9780071461979

672 pages Page 378 states as follows:

“The most useful members of this class of antibiotics (eg tetracyclines, lincomycin, erythromycin and chloramphenicol) DO NOT interact with components of eukaryotic ribosomcal particles and thus are not toxic to eukaryotes...” (emphasis added)

So as you can see this statement indeed does have support within the literature. The second sentence is a fact. There are any number of clinical studies that have shown the fluoroquinolones to have a much higher ADR rate than its compactors. So under mechanism of action it would not be unreasonable to compare the two. The fluoroquinolones have shown to have significant effects against eukaryotic topoisomearese II in vitro concentrations that are clinically significant. See:

Quinolone Antimicrobial Agents By David C. Hooper, Ethan Rubinstein

Edition: 3, illustrated Published by ASM Press, 2003 ISBN 1555812317, 9781555812317 485 pages page 69 states

“Several recent studies have described new quinolones that appear to have lost this selectivity for the bacterial type II enzymes and show significant effects against eukaryotic topoisomearese II in vitro concentrations that are clinically significant.”

Perhaps you could provide a rewrite on the talk page here that incorporates the above facts that you would find to be acceptable that we could discuss. You had stated that “It is grossly apparent that this article has been under significant pressure from biased and non-scientific contributors”. Where previously it had been under “significant pressure” to present the false and misleading information being provided by the various manufacturers. I think that the recent contributions by “non-scientific contributors” combined with the various edits by FG restored a neutral balance that was lacking from both versions. And I have no objections with working with you to correct any errors or omissions found within the mechanism section, nor do I believe that FG would either, if you have any current documentation that would support and justify such edits. Davidtfull (talk) 22:35, 14 March 2009 (UTC)

Opening paragraph

There has been a recent edit of the opening paragraph that had been changed as the reference used did not support the statment made, and then later removed as the statement was shown to be false, this statement was then reverted by the contributing editor back to its original form. The statement in question involves the assertion that:

"Since bacteria and humans unwind DNA with different enzymes, human enzymes are not affected."

The first change involved the removal of the words "human enzymes" as the reference did not support their use. The second change involved the removal of the statement as the liteature does not support it. Additionally it is contradicted within the article (with supporting citations). Having reverted this back to its original form the contributor has now asked that it be discussed here before being removed yet again.

I have recently made an edit that I believe resolves these issues and allows the statement, which has been modified as follows, to remain as it is now factual in nature, where as before it was not. That being:

"Since it is thought that bacteria and humans unwind DNA with different enzymes, most topoisomerases in eukaryotes are believed not to be affected."

If the editor is not willing to accept this compromise then I would ask that they provide documentation that clearly refutes the statements found elsewhere within the article (that proved the statement to be false to begin with) as well as citations that would support the inclusion of the term "human enzymes" in this context, as this was a replacement of the original text found within the citation that they had used, that being "topoisomerases in eukaryotes".

Additionally, considering the subject matter addressed by this contribution I think it would be best that it be moved from the introduction and placed within the mechanism section.Davidtfull (talk) 02:59, 24 July 2009 (UTC)

I recommend adding some additional different citations regarding this to the lead. I have read about a dozen citations regarding this matter as you know when editing the other quinolone article. From what I can tell individal quinolones differ in this regard, they do have interaction with human cells, DNA etc but is dependent on dose. The affinity for bacterial DNA is much higher though.--Literaturegeek | T@1k? 08:50, 26 July 2009 (UTC)

Serious reworking of this article needed.

The last edit, there were no changes, just my error on saving.

This edit began with disambiguation of organic quinolones from the antibacterial class. It extends to revisions that request a bias review. Until that could be done, all safety/SAE text was gathered under preexisting headings. Otherwise:

(1) The article needs to be retitiled, and/or split into two articles, where the organic structural class of quinolones is disambiguated from the antibacterial class which has taken its name (and which was earlier the sole emphasis of this article).

(2) It appears that at least one major contributing author/editor simply doesn't much like the overarching quinolone class of antibacterials: count the number of positive lines and compare that to the number of negative lines. And where is it pointed out in relation to safety testing, that relative to chronic drugs such as the statins, an antibacterial of any given class/type is rarely given in any regimen approaching chronic?

Problems acknowledged, quinolones still save lives, and are not themselves (as inanimate, bioactive agents) responsible for their misuse by physicians. If one wants the drug to be reliably used, you must simply tell the truth about it, not try to counterbalance misuses and shortcomings through imbalanced treatment.

Until a careful and balanced consolidating edit can be done, I gathered all safety study and serious adverse event (SAE) information from its various distributed earlier locations, putting it together under headings already created by other authors. Only most offendingly inaccurate statements were actually removed or strongly edited.

(3) Note, Trova and other NAPHTHYRIDINES need to be called out as structurally distinct antibacterial class, that is NOT, formally indicated as quinolones. Encyclopedias should not be intellectually sloppier than the (often admittedly weak) primary literature, but more careful, because its audiences are less informed.

Bottom line, much more work is needed to make this a balanced, first-class article. Prof D — Preceding unsigned comment added by Meduban (talk • contribs) 01:43, 14 April 2011 (UTC)

Serious reworking of this article unneccasary and inappropriate.

This article was the end result of YEARS worth of factual research and intense (and at times brutal) negotiations with the various pharmacology editors on wikipedia, and patient advocates, who ALL had worked together to present a well researched, documented and balanced article.

The revisions made by Prof D (Meduban) have been removed and the article reverted to the original state prior to these extensive edits, as the edits are contrary to the scope and purpose of this article as well as negated the various compromises reached after years of fruitfull debate concerning the content of this article.

As per Prof D's suggestion within this talk page, a new article was created entitled "2- and 4-quinolones", (http://wiki.riteme.site/wiki/2-_and_4-Quinolones) where the edits made by Prof D were moved and the verbage relating to the original quinolone article (that he objected to) were deleted from that article.

If Prof D wishes to discuss his own bias opinions and apparent diagreements with the compromises already reached in the pasts regarding the current quinolone article, (where the identical concerns he/she raises that had already been raised and addressed), he/she is welcome to do so on this talk page, rather than haphazardly editing the article as extensively as he had done.

Ignoring all of the previous settled debates, thereby negating the years of hard work by the various pharmacological editors, and raising them yet again (after they had already been settled) does nothing to improve this article. Nor does tagging every heading inappropriatedly simply because a person may disagree with the content. Such disagreements are to be addressed on the talk page rather than by issuing mutiple and frivolous tags within an article.Davidtfull (talk) 00:17, 6 May 2011 (UTC)davidtfull

"General Avoidance"

I removed the sentence at the beginning of the artice about "general avoidance" of fluroquinolones. Whatever the good intentions of the person entering this sentence into the article, the requirement for a neutral point of view does not allow only one side of an issue to be presented in this way. Specific fluoroquinolones are a first tier recommendation of The British Society for Antimicrobial Therapy for CAP: of the European Respiratory Society, the European Society of Clinical Microbiology, and the the European Society of Intensive Care Medicine for certain subsets of HAP; of the Infectious Disease Society of America for mild to moderate community acquired intra-abdominal infections, and of the IDSA for cather-associated urinary tract infections. — Preceding unsigned comment added by Alfred Bertheim (talk • contribs) 22:00, 14 March 2012 (UTC)

Excessive Digressions Compromise Readability and Overall Quality

This article is one of many in Wikipedia describing drugs classes or chemicals with demonstrated or putative toxicity. In the vast majority of these articles, discussion of the various industrial uses, history, and technical aspects of the substance(s) in question is broken into various subheadings, including one focused on the toxicity issue. In a few cases, such as the current one, a separate Wikipedia article focuses exclusively on the drug or chemical class's safety profile.

The present article also has a section on adverse effects, but lengthy digressions (sometimes taking up most of the section) on toxicity occur in each of the sections below.

Introduction
• Medical Uses
• Contraindications
• Pharmacology
• Mechanism of Action
• Interactions
• Social and Economic Impact (which mentions ONLY toxicity, and not the uses of these drugs)
• Patent Extensions
• Legal Status
• Boxed Warnings
• Generations

Furthermore, the toxicities that have been seen with these compounds are the subject of an entirely separate and lengthy "toxicity of fluoroquinolones" article, which simply could be incorporated into this article by reference.

As an example of a clearer, more balanced article style, I would point to the Wikipedia articles on other controversial drug classes such as antidepressants and atypical antipsychotics. In each case the safety issues are described within the broader context of the history of the compounds, how they are used, and the science behind them. Discussion of side effects is limited primarily to a section entitled "Adverse Events", just as discussion of patent issues is restricted to the patent issues section. Accordingly, these articles are characterized by high readability and broad information content, and could serve as a template for a major rewrite of the present article. — Preceding unsigned comment added by Alfred Bertheim (talk • contribs) 08:46, 10 September 2012 (UTC)

3x increase in Achille's Tendon ruptures

I think it was find the way I left it @Jytdog:. It is a rare side effect, but a serious one. Having both the relative risk and the absolute risk there is more informative than having only one, and neither is misleading in the presence of the other. After all ,these drugs do have a boxed warning. Formerly 98 (talk) 20:27, 22 August 2014 (UTC)

OK, not worth fighting about. self reverted. Jytdog (talk) 22:48, 22 August 2014 (UTC)

thanks. Not to get into [[WP:OWN}} but I spent a lot of time thinking about the realistic assessment of the risks of these compounds while rewriting these aricles post-Davidtfull. The risks were horrifically overstated, but I'd probably think twice about taking these drugs for a trivial infection if over age 65 or so, especially if athletically active or recently on corticosteroids. Formerly 98 (talk) 23:14, 22 August 2014 (UTC)

Sedative hypnotic withdrawal

The first reference cited in support of this claim (Unseld et al) describes EEG measurements but contains no examples of withdrawal symptoms. Furthermore it is a primary research citation and does not meet the requirements for sourcing of health-related content outlined in WP:MEDRS.

The second reference is a case report. Case reports are explicitly called out as "a form of anecdote falling below minimal levels of medical evidence" in WP:MEDRS.

The third reference is a primary research report. It does not meet the standards for sourcing of health-related content outlined in WP:MEDRS.

The fourth citation does not describe any examples of "sedative hypnotic withdrawal" induced by FQs.

2601:643:8100:8AF4:C4A2:D991:C7E0:9B17 (talk) 03:54, 18 October 2015 (UTC)

OK, fair enough, that if its not in the Cipro package insert it ain't so. I'll look into finding some better references. Not the Ashton Manual, we've seen that one rejected already, although I don't know any Brit who didn't use it or a variation of it when they were in school. This is a bit frustrating since from the addictionologist's or geriatrician's viewpoint my statement is common knowledge, on the level of "cats have been domesticated for many years".Trilobitealive (talk) 04:34, 18 October 2015 (UTC)

"FQAD"

FQAD is an acronym invented for the purpose of a single FDA document to describe people who suffered long term disability, specifically after being treated with FQs for one of three indications in which antibiotic treatment is not normally beneficial.

The use of this acronym in a single document does not represent a sea change in the scientific consensus regarding the use of these drugs or a sudden recognition of a new syndrome. IDSA and EFSA have long recommended that these drugs be reserrved for relatively severe infections, the EFSA in particular (and as noted, I believe, in the article) noting the "potential for adverse effects. Elsewhere in the article the potential for atrythmia, peripheral neuropathy, and achilles tendon damage are discussed, the latter at some length.

Lets follow the rules here. There are literally hundreds of papers and regulatory documents out there discussing FQ safety. Writing multiple paragraphs and a complete stand alone article about one of them because it happens to align with a single editor's viewpoint (specifically one whose pseudoname suggests a personl connection with the subject) violates both WP:UNDUE and the COI policy. 2600:1010:B055:3C74:C3C7:D622:852D:C8AF (talk) 00:37, 22 October 2015 (UTC)

You're an IP editor or group of related IP editors so I'm posting this here instead of the various talk pages on the IP accounts.

First see the essays Wikipedia:No reliable sources, no verifiability, no article and WP:FATRAT. (You will notice that these are common sense guidelines, not rules. However their points are very important.) Going back to the discussion of the deletion: The material you deleted seems to add to the article. The wikilinked article you claim should be deleted seems to me to be verifiable and reliably sourced. Therefore your edit, appears to be erroneous. Your discussion about your edit sounds like an opinion to me. And it appears part of a bigger set of opinions which appear to me to be your point of view. You have your point of view and I have mine but regardless of that please stop deleting sourced information. The usual way things are done in Wikipedia is that to move the article toward being better we would help each other find better sourcing and better wording, not slash and burn everything that we don't like.

Second, since this latest deletion appears to be part of the point of view pattern I just can't get interested right now in an editor who may or may not have a personal connection with another subject. My interest is instead drawn to trying to understand why an editor or related group of editors seems committed to applying a Procrustean reading of recommendations (not rules) for wikipedia referencing. He/she/they have deleted a pretty sizable series of various edits (some of which were mine) on the general subject of informing the reader about risks and side effects of a particular family of medicines. That sounds more like his/her/their point of view than anything else. I am a believer in minding my own business so this is elucidation, not criticism.

Third, I suppose by "rules" you mean the guideline you cited to delete some of my edits on the last section you put up here. If you've forgotten, here is it's link. WP:MEDRS It is a guideline and not a rule. You will notice that it is tagged with a brief notation that it should be treated with common sense. Trilobitealive (talk) 22:55, 22 October 2015 (UTC)

We do things by consensus here, and while MEDRS is a Guideline and not a Policy, it is one of the most extensively discussed Guidelines on Wikipedia and represents the consensus of a large number of editors. The sourcing rules that have been hammered out there through extensive discussion are not mere suggestions, and "use common sense" is not synonymous with "ignore this guideline anytime it gets in the way of an edit you want to make"

NPOV is a policy and WP:UNDUE is part of that. I recognize there are people whose lives have been destroyed by these drugs, and I greatly sympathize with them, but pretty much every drug in existence has terrible side effects in a small percentage of people, as well as benefiting or saving the lives of others. An encyclopedia has to balance both of these aspects. Thats what MEDRS, NPOV, and WP:UNDUE are there for.

2600:1010:B06B:11F9:EB30:3CF2:EEF0:BAE4 (talk) 02:00, 23 October 2015 (UTC)

Too much drama here for me. Look up WP:SPA while you're reading guidelines. Trilobitealive (talk) 01:56, 24 October 2015 (UTC)

Merge into 4-Quinolones?

Reasons to merge, aside from the general goal of helping readers:

• A lot of content duplication.
• I recently cleaned up 4-Quinolones, and prefer not to duplicate that work.
• It is the 4-Quinolones where most of the drug action is at, apparently.

Reasons maybe not to: I am not a super-expert on this area, so possibly missed something major. --Smokefoot (talk) 17:19, 23 July 2017 (UTC)

Question: do you think there is enough content to keep a separate article focusing on the chemistry alone? If so, I'd keep that at 4-Quinolones, merge the relevant (med/pharm) content into Quinolone, and rename Quinolone to Quinolone antibiotics—by analogy with β-lactam antibiotics, for instance. (Great work, by the way.) Fvasconcellos (t·c) 18:26, 23 July 2017 (UTC)

Thanks for the suggestions. Here is a possible plan.

• • Step 1: separate 2- and 4-quinolones (done this AM), creating 2-Quinolone (not plural, a narrow org. chem. topic) and 4-Quinolones (plural, grab-bag of org chem but mostly med chem)
  • Step 2: merge Quinolone into 4-Quinolones (what we are talking about now).
  • Step 3A: (your implied idea) shift of med chem content of 4-quinolones into quinolone antibiotics.
  • step 3B: create 4-Quinolone (singular, narrow organic chem topic, analogous to 2-Quinolone). 4-Quinolone is a fundamental organic compound, it doesnt need to be long.
  • Step 4: make Quinolone/Quinolones into a disambiguation site, pointing to three places 2-Quinolone, 4-Quinolone, and Quinolone antibiotics.

--Smokefoot (talk) 20:44, 23 July 2017 (UTC)

that sounds great. Unfortunately, you've created a cut-and-paste move while implementing it. Please hold off on further edits to this page and 4-Quinolones for a second while I merge their histories. Ah, actually, you know what? Never mind. There's too much parallel history between the articles, I think a regular merge works just fine here. I don't think "step 3A" is even necessary here; I'd just delete the redirect that currently sits at Quinolone antibiotic and move 4-Quinolones over there. Fvasconcellos (t·c) 00:39, 25 July 2017 (UTC)

Yes, the two articles were parallel universes. Please keep an eye on this process because these are important drugs and probably get a lot of hits. I am worried abouta lot of double redirects and much duplication in the merged article. It appears that the med chemists use 4-quinolone loosely to include other heterocyclic cores. I want to eventually create 4-Quinolone as a stand-alone reference point so that the drug article does not need to cover such. You are always welcome to intervene, warn, advise especially since I am so focused on content and can mess up on Wiki-tech. --Smokefoot (talk) 02:09, 25 July 2017 (UTC)