Quinolone


Quinolone

The quinolones are a family of synthetic broad-spectrum antibiotics. The of the group is nalidixic acid. The majority of quinolones in clinical use belong to the subset of fluoroquinolones, which have a fluoro group attached the central ring system, typically at the 6-position.

Mechanism

Quinolones and fluoroquinolones are bactericidal drugs, actively killing bacteria. Quinolones inhibit the bacterial DNA gyrase or the topoisomerase IV enzyme, thereby inhibiting DNA replication and transcription. Quinolones can enter cells easily via porins and therefore are often used to treat intracellular pathogens such as "Legionella pneumophila" and "Mycoplasma pneumoniae". For many gram-negative bacteria DNA gyrase is the target, whereas topoisomerase IV is the target for many gram-positive bacteria. Eukaryotic cells do not contain DNA gyrase or topoisomerase IV.

Adverse effects

In the fall of 2004, the Food and Drug Administration upgraded the warnings found within the package inserts for quinolones regarding potentially serious adverse reactions. It is important to note, that pharmaceutical companies claim that the incidence of the following is quite rare, with occurrences at less than one per ten thousand person-years:However, many people who have been adversely effected dispute that the adverse reactions are rare and they may in fact be much more widespread than previously thought. cite web|title=IDSA: Achilles Tendon Rupture after use of antibiotics|author=Maury M. Breecher, PhD, MPH|date=October 17, 2003|publisher=Doctor's Guide, Global Edition|url=http://www.pslgroup.com/dg/23C5CA.htm|accessdate=2007-07-01]

Side effects from fluoroquinolones can be mild and short lived or they can be severe and long lasting after therapy has been discontinued. If side effects effecting the central nervous system, peripheral nervous system or muscular system occur the patient should discontinue therapy and consult with their doctor. The side effects from fluoroquinolones include tingling, anxiety, numbness, twitching, joint pain, muscle pain, tendinitis, fear, blurred vision, memory loss, diarrhea, severe panic attacks, insomnia, tear of achilles tendon, confusion, impaired concentration, burning pain, carpal tunnel syndrome, nightmares, confusion, tachycardia, nausea, palpitations, hyperesthesia, fatigue, depersonalisation, pins and needles sensation, muscular spasms, tremors, headaches, agitation, hallucinations, psychosis, tinnitus, skin rash, hair loss, abdominal pain, visual disturbances.cite journal | author =Cohen JS | year =2001 | month =Dec | title =Peripheral Neuropathy Associated with Fluoroquinolones | journal =Ann Pharmacother | volume =35 | issue =12 | pages =1540–7 | pmid =11793615 | url =http://fqvictims.org/fqvictims/News/neuropathy/Neuropathy.pdf | format =PDF | doi =10.1345/aph.1Z429 ]

*Peripheral neuropathy (nerve damage): "Rare cases of sensory or sensor motor axonal polyneuropathy affecting small and or large axons resulting in paresthesias, hypoaesthesias, dysesthesias, and weakness have been reported in patients taking quinolones. Therapy should be discontinued if the patient experiences symptoms of neuropathy, including pain, burning, tingling, numbness and/or weakness, or is found to have deficits in light touch, pain, temperature, position sense, vibratory sensation, and/or motor strength in order to prevent the development of an irreversible condition." [cite journal | author =Hedenmalm K |coauthors=Spigset O | year =1996 | month =Apr | title =Peripheral sensory disturbances related to treatment with fluoroquinolones | journal =J Antimicrob Chemother | volume =37 | issue =4 | pages =831–7 | pmid =8722551 | url =http://jac.oxfordjournals.org/cgi/reprint/37/4/831 | format =PDF | doi =10.1093/jac/37.4.831 ]

*Tendon da
tendinitis or tendon rupture had been excluded. Tendon rupture can occur during or after therapy with quinolones." On July 8, 2008, the FDA requested manufacturers to include a black box warning for tendon damage. [ [http://www.fda.gov/bbs/topics/NEWS/2008/NEW01858.html FDA Press release] ]

*Kidney stones due to loss of Oxalobacter formigenes [ [http://www.urologystone.com/CH18WhatsNew/2001AUA.html] - Interim reference; cites Troxel SA, Low RK. Intestinal Oxalobacter Formigenes Colonization Urinary Oxalate Levels in Calcium Oxalate Stone Formers. Journal of Urology 165:245A, 2001. "(Please replace with that citation if the full text of the article agrees with the linked summary)"]

Interactions

Caffeine, nonsteroidal antiinflamatory drugs, Theophylline and corticosteroids enhance the toxicity of fluoroquinolones. [cite web
url= http://www.medscape.com/druginfo/monoinfobyid?cid=med&monotype=druginter&monoid=1443&mononame=QUINOLONES%2FCORTICOSTEROIDS&drugid=17879&drugname=Avelox+Oral&intertype=mod|title= Moderate Interaction: Quinolones/Corticosteroids |accessmonthday= Sep 2|accessyear= 2008|publisher= Medscape
] [cite web
url=http://www.medscape.com/viewarticle/418295_4|title=Fluoroquinolone Adverse Effects and Drug Interactions |accessmonthday= Sep 2|accessyear= 2008|publisher= Medscape
]

Other drugs which interact with fluoroquinolones include Antacids, Sucralfate, Probenecid, Cimetidine, Probenecid, Warfarin, Antiviral agents, phenytoin, cyclosporine, rifampin, pyrazinamide, and cycloserine. [cite web
url=http://www.medscape.com/viewarticle/418295_4|title=Fluoroquinolone Adverse Effects and Drug Interactions |accessmonthday= Sep 2|accessyear= 2008|publisher=Medscape
]

Resistance

Resistance to quinolones can evolve rapidly, even during a course of treatment. Numerous pathogens, including "Staphylococcus aureus", enterococci, and "Streptococcus pyogenes" now exhibit resistance worldwide. [M Jacobs, Worldwide Overview of Antimicrobial Resistance. International Symposium on Antimicrobial Agents and Resistance 2005.] Widespread veterinary usage of quinolones, in particular in Europe, has been implicated.Fact|date=May 2008

There are three known mechanisms of resistance. [A Robicsek, GA Jacoby and DC Hooper, The worldwide emergence of plasmid-mediated quinolone resistance. 2006. The Lancet Infectious Diseases 6-10:629-640] Some types of efflux pumps can act to decrease intracellular quinolone concentration. In gram-negative bacteria, plasmid-mediated resistance genes produce proteins that can bind to DNA gyrase, protecting it from the action of quinolones. Finally, mutations at key sites in DNA gyrase or topoisomerase IV can decrease their binding affinity to quinolones, decreasing the drug's effectiveness.

Generations

The quinolones are divided into generations based on their antibacterial spectrum.cite journal |author=Ball P |title=Quinolone generations: natural history or natural selection? |journal=J. Antimicrob. Chemother. |volume=46 Suppl T1 |issue= |pages=17–24 |year=2000 |pmid=10997595 |doi= |url=http://jac.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=10997595] cite web |url=http://www.aafp.org/afp/20000501/2741.html |title=New Classification and Update on the Quinolone Antibiotics - May 1, 2000 - American Academy of Family Physicians |accessdate=2008-03-18 |format= |work=] The earlier generation agents are, in general, more narrow spectrum than the later ones.

1st generation

* cinoxacin (Cinobac)cite web |url=http://www.aafp.org/afp/20020201/455.html |title=Quinolones: A Comprehensive Review - February 1, 2002 - American Family Physician |format= |work= |accessdate=]
* flumequine (Flubactin) (Veterinary use)
* nalidixic acid (NegGam, Wintomylon)
* oxolinic acid (Uroxin)
* piromidic acid (Panacid)
* pipemidic acid (Dolcol)
* rosoxacin (Eradacil)

2nd generation

* ciprofloxacin (Ciprobay, Cipro, Ciproxin)cite web |url=http://www.medscape.com/viewarticle/410872_6 |title=Clinical Usefulness Of Quinolones |format= |work= |accessdate=]
* enoxacin (Enroxil, Penetrex)
* fleroxacin (Megalone, Roquinol) (withdrawn)
* lomefloxacin (Maxaquin)
* nadifloxacin (Acuatim, Nadoxin, Nadixa)
* norfloxacin (Lexinor, Noroxin, Quinabic, Janacin)
* ofloxacin (Floxin, Oxaldin, Tarivid)
* pefloxacin (Peflacine)
* rufloxacin (Uroflox)

3rd generation

* balofloxacin (Baloxin)
* gatifloxacin (Tequin (withdrawn), Zymar) Sometimes reported as fourth generation. [PMID 17893419]
* grepafloxacin (Raxar) (withdrawn)
* levofloxacin (Cravit, Levaquin)
* moxifloxacin (Avelox,Vigamox) Sometimes reported as fourth generation.cite journal |author=Miravitlles M, Anzueto A |title=Moxifloxacin: a respiratory fluoroquinolone |journal=Expert Opin Pharmacother |volume=9 |issue=10 |pages=1755–72 |year=2008 |month=July |pmid=18570608 |doi=10.1517/14656566.9.10.1755 |url=]
* pazufloxacin (Pasil, Pazucross)
* sparfloxacin (Zagam)
* temafloxacin (Omniflox) (withdrawn)cite web |url=http://www.medscape.com/viewarticle/410872_4 |title=Classification Of Quinolones By Generation |format= |work= |accessdate=]
* tosufloxacin (Ozex, Tosacin)

4th generation

* clinafloxacin
* garenoxacin (Geninax)
* gemifloxacin (Factive)
* sitafloxacin (Gracevit)
* trovafloxacin (Trovan) (withdrawn)
* prulifloxacin (Quisnon)

In development

* ecinofloxacin [cite web|url= http://www.medindia.net/articles/Fluoroquinolones.asp|title= Fluoroquinolones|accessmonthday= Sep 2|accessyear= 2008|author= Dr. T.R.RAMANUJAM. M.D.|publisher= Medindia]

Veterinary use

The quinolones have been widely used in agriculture and several agents exist which have veterinary but not human use.
* danofloxacin (Advocin, Advocid) "(for veterinary use)"
* difloxacin (Dicural, Vetequinon) "(for veterinary use)"
* enrofloxacin (Baytril) "(for veterinary use)"
* ibafloxacin (Ibaflin) "(for veterinary use)"
* marbofloxacin (Marbocyl, Zenequin) "(for veterinary use)"
* orbifloxacin (Orbax, Victas) "(for veterinary use)"
* sarafloxacin (Floxasol, Saraflox, Sarafin) "(for veterinary use)"

External links

* [http://www.cdc.gov/ncidod/dhqp/ar_lab_quinlolones.html Fact Sheet: Quinolones]
* [http://www.fluoroquinolones.org "The Flox Report" An investigative approach to the true toxicity of quinolone antibiotics.]
* [http://www.fqresearch.org Research on Adverse Effects of Fluoroquinolones]
* [http://fqframes.org/fqframes/News/Fluoroquinolone%20Induced%20Tendinopathy/smj9206_11_harr-01.html "Fluoroquinolone-Induced Tendinopathy: What do we know?" Richard M. Harrell, MD.]
* [http://fpnotebook.com/ID160.htm Fluoroquinolones] "Family Practice Notebook" entry page for Fluoroquinolones
* [http://www.infectio-lille.com/diaporamas/invites/struct-act-duatb05-bryskier.pdf Structure Activity Relationships] "Antibacterial Agents; Structure Activity Relationships," André Bryskier MD

References


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Look at other dictionaries:

  • quinolone — ● quinolone nom féminin Médicament d usage courant assimilé aux antibiotiques, utilisé notamment dans les infections urinaires (nom générique) …   Encyclopédie Universelle

  • Quinolone — Structure de base des quinolones: le groupe R (bleu) est assez souvent un groupe pipérazine; si la molécule est liée à un fluor (rouge), il s agit d une fluoroquinolone. Les quinolones et fluoroquinolones[1] …   Wikipédia en Français

  • quinolone — noun Etymology: quinoline + one Date: 1936 any of a class of synthetic antibacterial drugs that are derivatives of hydroxylated quinolines and inhibit the replication of bacterial DNA …   New Collegiate Dictionary

  • quinolone — noun a) Any of several isomeric ketones derived from quinoline b) Any of a range of broad spectrum antibiotics, related to nalidixic acid, based on this structure See Also: fluoroquinolone …   Wiktionary

  • quinolone — quin·o·lone kwin ə .lōn n any of a class of synthetic antibacterial drugs that are derivatives of hydroxylated quinolines and inhibit the replication of bacterial DNA esp FLUOROQUINOLONE * * * n. one of a group of chemically related synthetic… …   Medical dictionary

  • quinolone — [ kwɪnələʊn] noun an antibiotic derived from quinoline and used chiefly against Gram negative organisms. Origin 1930s: from quin (in quinoline) + one …   English new terms dictionary

  • quinolone — quin·o·lone …   English syllables

  • quinolone — n. one of a group of chemically related synthetic antibiotics that includes ciprofloxacin, nalidixic acid, and ofloxacin. These drugs act by inactivating an enzyme, DNA gyrase, that is necessary for replication of the microorganisms and are often …   The new mediacal dictionary

  • quinolone — ˈkwinəlˌōn noun ( s) Etymology: quinoline + one : any of a class of synthetic antibacterial drugs that are derivatives of hydroxylated quinolines and inhibit the replication of bacterial DNA …   Useful english dictionary

  • Fluoro-quinolone — Quinolone Structure essentielle de tous les antibiotiques quinolones: le groupe R (bleu) est généralement un groupe pipérazine; si la molécule est liée à un fluor (rouge), il s agit d une fluoroquinolone Les quinolones et fluoroquinolones[1] …   Wikipédia en Français


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