Flumequine and Balofloxacin

Flumequine and BalofloxacinMade byLAB GROUP F2Lab InstructorsT.A/Spring 2015Table of ContentsIntroduction on (Flumequine) pg. 3 and (Balofloxacin) pg. 4Discussion on (Flumequine) pg. 5, 6, 7 and (Balofloxacin) pg. 8, 9, 10Conclusion pg. 11Reference pg. 12FlumequineThe first of the quinolone family is the nalidixic acid. The drug was followed by the floroquinolones including flumequine which is a initiatory generation agent in the floroquinolones. The first generation including flumequine had a variety of problems such asLimited natural processpoor distributiontendon rupturesHepatotoxicity and elongate effect on neurological disorders ex myasthenia gravisAll of the first generation drugs were used for the treatment of infections in the urinary tract. The benzo quinolzine (flumequine) was invented in 1973 by (rikker labs) a german inventors. Flumequine is known to be the first of the quinolone family to include a fluoride at degree centigrade subject six on the skeleton of the quino lone compound. Although flumequine is basic totallyy the first of all floroquinolones it is frequently overlooked upon classification of this class of drugs through generations it was omitted from the list. It is more often used for the treatment of farm animals and on certain cases pets. And as follows the use in humans is for infections in the urinary tract. It was originally used only for urinary tract infections until reports of toxicity were filed reporting anaphylactic shock and degrees of damage in the liver. The (FDA) solid food and drug administration made a request on all the quinolone and floroquinolone boxes to be delivered to contain a black boxed warning thus, notifying the risks of sudden ruptures in the tendon which basically includes the flumequine. As well letters were sent to physicians based on the FDA&aposs request to notify the doctors. The tendon complications were also exhibited in flumequine.The legal age of floroquinolone generic versions did not include t he black boxed warning in 2009 September as well some reports were filed to claim that this information was never distributed or sh ard among pharmacists and some products to this day still are shipped without the warning or medication guide that the physicians and pharmacists merchant ship distribute.Uses (licensed)Infections in the urinary tractBalofloxacinBalofloxacin is often substantial as an anti bacteriuml agent. It has a broad spectrum bactericidal act. It is less toxic than other fluoroquinolones. The distinction between a quinolone drug and a fluoroquinolone drug is the summation of fluorine to the basic pharmacophore, which causes a fluorinated drug. Quinolones and fluoroquinolones terms are often used interchangeably regardless of this distinction. Balofloxacin is a third generation fluoroquinolone.A meta-analysis of skin infections and fluoroquinolones showed that the fluoroquinolones are more associated with unfavorable reactions than beta lactam. However, the incr ease was due to a slight to moderate rate of nausea and diarrhea spunkyer. Enough to cause serious view effects withdrawal of the trial occurred at similar rates.Rarely, fluoroquinolones have been associated with serious and adverse effects on the musculoskeletal governing body, cardiovascular system, central nervous system and peripheral nervous system, circulatory system, the maxillofacial system, endocrine system, gastrointestinal system the urological system, liver, brain, skin, and sensory systems such as sight, hearing, touch, smell and taste. After a single acid toxic reactions had been reported to occur.UsesUncomplicated infections of the urinary tractChemical structureFlumequineChemical structure and formula C (14) H (12) F (1) N (1) O (3)IUPAC name9-fluoro -6, 7 dihydro -5 methyl -1 oxo -1H, 5H -benzo quinolizine -2- carboxylic acidMode of actionFlumequine is in the first place an antibiotic that is broad spectrum and mostly active against gram positive bacteria and g ram negative. Mechanism works through the inhibition of gyrase deoxyribonucleic acid, topoisomerase specifically type 2 and type 4 they are enzymes that are responsible for bacterial desoxyribonucleic acid segregation therefore by inhibiting them the bacteria cannot replicate hence, inhibition of electric cell division. This mechanism might also alter mammalian cell division. Basically the drugs of high activity could lead to toxic effects in mammals. The report of DNA damage was first filed in 1986, its mechanism of cytotoxicity is still unknown.Dosage formsFor veterinary forms spontaneous solutions (10-20%) prescription requiredFor human forms Oral tablets (400mg) notice it is discontinued 20% solution Tablet formulation stoppedSynthesis of flumequineStructure activity family (SAR)The fluorine that is present at carbon number six which enhances the inhibition of gyrase and cellular penetration.The carbon number seven constituent was set to control cell permeability according t o the properties of the constituent.Substitution of N number 1 is essential in obtaining the anti-bacterial properties.The introduction of a butyl group at N number 1 enhances the activity against the gram positive bacteria and little or stripped-down reduction of activity against gram negative bacteria.At position two the accession of nitrogen did show an improvement of the pharmacokinetic properties.At positions 4 and 3 they do have a link with the keto and carboxylic group which is an essential thing for bond to the gyrase DNA.At position number 5 the renewal by small groups like amino, nitro, halogens and alkyl groups could improve the tissue distribution and absorption. Though suggestions were raised that the substitution at position 5 could falling off the anti-bacterial properties.At position 6 the substitution by F, H, Br, Cl, nitro, methyl and Cyanide would actually increase the potency of anti-bacterial activity by means of improving the bind and penetration abilitie s.MetabolismFlumequine is known to have good absorption thus, well absorbed and is mainly excreted in dejection and urine as a glucuronide conjugates according to the parent drug and active ingredient of metabolism which is flumequine 7-hydroxy. The drug is eliminated within 168 hours after dosing. Major residue was found in chickens, pigs and sheep to be in the form of flumequine 7-hydroxy it was found in minimal amounts. The detection of the parent drug was only found in trout. Metabolism can be summarized as well absorbed and metabolized in the liver.BalofloxacinIUPAC1-Cyclopropyl-6-fluoro-8-methoxy-7-(3-methylaminopiperidin-1-yl)-4-oxoquinoline-3-carboxylic acidSynthesisMode of actionFirst and second generation fluoroquinolone selectively inhibit the theatre of ligase topoisomerase II, leaving two areas nuclease full. This modification, combined with the constant action in the bacterial cell by topoisomerase II, results in fragmentation of DNA through nuclease activity domain s of intact enzymes. fluoroquinolones that are third and fourth generation are more selective for the ligase domain topoisomerase IV and therefore improved the gram positive coverage.Fluoroquinolones can land cells through porins easily thus, could be used for the treatment of pathogens that are intracellular such as Mycoplasma pneumoniae and Legionella pneumophila. Too many bacteria that are gram-negative, the backside is the DNA gyrase, in turn the topoisomerase IV is the target of many Gram-positive bacteria. Some compounds of this class were found to inhibit the synthesis of mitochondrial DNA.Dosage formsTablets 100-400 mg ad-lib examMetabolismPharmacokinetics of balofloxacin, the new fluoroquinolone, was a study conducted on mice, dogs and rats through liquid chromatography (high-performance). The bioavailabilities oral means of balofloxacin it was obtained through calculation of the AUC (area under the curve) after intravenous and oral in mice, rats and dogs 87.50 and 87.7 3%, respectively, suggesting that was absorbed almost entirely balofloxacin in rats and dogs, but not in mice after single oral administration. The average elimination half-life in plasma after intravenous injection in mice, rats and dogs are 0.92, 1.33 and 6.38 hours, respectively. I mean cumulative urinary excretion rate unchanged balofloxacin within 24 hours of oral administration of balofloxacin in dogs, mice and rats respectively. May secrete a small part of the metabolism in the urine as glucuronide balofloxacin and N-desmethyl balofloxacin in these species. After oral administration of balofloxacin in a dose of 100 mg / kg in rats, and was for a long period of absorption compared with those after administration in doses of 5 and 20 mg / kg. The plasma concentration-time profiles and pharmacological parameters of balofloxacin in male mice similar to those found in female mice, suggesting a lack of sex-related differences. Once a day for 21 days, multiple departments were not a ffected by this drug in mice of balofloxacin formations.Structure activity relationship (SAR)The fluorine that is present at carbon number six which enhances the inhibition of gyrase and cellular penetration.The carbon number seven constituent was found to control cell permeability according to the properties of the constituent.Substitution of N number 1 is essential in obtaining the anti-bacterial properties.The introduction of a butyl group at N number 1 enhances the activity against the gram positive bacteria and little or minimal reduction of activity against gram negative bacteria.The addition at position two of nitrogen did show an improvement of the pharmacokinetic properties.They do have a link at positions 4 and 3 with the keto and carboxylic group which is an essential thing for binding to the gyrase DNA.The substitution at position number 5 by small groups like amino, nitro, halogens and alkyl groups could improve the tissue distribution and absorption. Though suggestions were raised that the substitution at position 5 could decrease the anti-bacterial properties.The substitution at position 6 by F, H, Br, Cl, nitro, methyl and Cyanide would actually increase the potency of anti-bacterial activity by means of improving the binding and penetration abilities.ConclusionFlumequineIt is a first generation fluoroquinoloneWell absorbed orally and metabolized hepatically (glucuronide conjugates)Discontinued due to dangerous adverse effects such as hepatotoxicityVeterinary use onlyBlack box warningIs used for UTI but discontinued in humansMechanism of action is inhibition of DNA gyrase, less selective than third generation drugs and lower gram positive activityWas administered orally as tablets for human use but discontinued and mainly now as solutions for veterinary useExcreted in feces and urine.BalofloxacinIt is a third generation fluoroquinoloneWell absorbed orally and minimal hepatic metabolismIt is very useful because it has less adverse effects than o ther fluoroquinolonesHuman useNo black box warning due to minimal side effectsMainly used for uncomplicated UTISame mechanism of action of fluoroquinolones (Inhibition of DNA gyrase) more selective and improved gram positive activity due to 3rd generation propertiesOrally administered in the form of tabletsExcreted in feces and urineReferenceChemspider, Flumequine Available at http//www.chemspider.com/Chemical-Structure.3257.html (Accessed 12 April, 2015)FAO, Food and tillage Organization of The United States, Flumequine, Available at http//www.fao.org/docrep/w8338e/w8338e0a.htm (Accessed 12 April, 2015)NCBI, Structure Activity relationships of The Fluoroquinolones, Anti microb Agents Chemother (1989) pages 131-135 Available at http//www.ncbi.nlm.nih.gov/pmc/articles/PMC171443/(Accessed 12 April, 2015)World Public Library, Flumequine Available at http//www.netlibrary.net/articles/flumequineMode_of_action (Accessed 12 April, 2015)Medicine India. Balofloxacin Pharmacology. Available at https//www.medicineindia.org/pharmacology-for-generic/2923/balofloxacin(Accessed 13 April, 2015)NCBI. Pharmacokinetics of the new fluoroquinolone balofloxacin in mice, rats, and dogs. (1995). Available at http//www.ncbi.nlm.nih.gov/pubmed/7646579(Accessed 13 April, 2015)WHO. Medical reference publication. (2005). PDF, Available at http//www.netlibrary.net/eBooks/WPLBN0000173166.aspx(Accessed 13 April, 2015)Drugs and Pharmacology. Balofloxacin. (2013). Available at http//drugsandpharmacology.blogspot.com/2013/03/balofloxacin.html(Accessed 13 April, 2015)1