A presentation on quinolones

This is a presentation on Quinolones antibiotics. it contains what is quinolones, it's history, chemistry, SAR, Mechanism of Action, bacterial cell & drug targets, classification, Summary of antimicrobial spectrum of quinolones, mechanism of resistance to quinolones, pharmacokinetics, indication, side-effects, adverse effect & available Pharmaceutical preparation of Quinolones in Bangladeshi market.

1. Quinolones Welcome to a Presentation on 1

2. Presented By: Group : 4 Bipasha Belal (121033) Protic Jodder (121031) MD. Sabbir Hossain (121026) Bikash Kumar Ghosh (121016) 3 rd Year ; 1 st Semester Department of Pharmacy Jessore University of Science & Technology Presented To: MD. Rafiqul Islam Lecturer Department of Pharmacy Jessore University of Science & Technology 2

3. Quinolones Broad spectrum antibiotics. Play an increasingly important role in treatment of multi-drug resistant bacterial infections. They are widely used because of their relative safety, availability both orally & parenterally and their favorable pharmacokinetics. Quinolone drugs: norfloxacin, ciprofloxacin, ofloxacin, levofloxacin, trovafloxacin etc. 3

4. History A group of synthetic antibacterial agents mainly effective against G- ve . Nalidixic acid first member introduced in 1964 for urinary and GIT infections. Its congeners Oxolinic acid and rosoxacin with more potency in 1970s. Second generation called fluoroquinolones with extended spectrum and systemic effects in 1980s. Since then many synthesized with useful spectrum . 4

5. Quinolones : Chemistry Quinolones are synthetic antimicrobial agents. Parent drug: nalidixic acid. Quinolones are widely used for urinary tract infections. Fig: nalidixic acid or, 1-Ethyl-7-methyl-4-oxo-[1,8]naphthyridine-3-carboxylic acid 5

6. Quinolones : Chemistry… Fig: Essential structure of all quinolone 6

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8. Mechanism of Action Quinolones have dual MOA: Inhibition of bacterial DNA Gyrase (Topoisomerase II) Formation of quinolone-DNA- Gyrase complex Induced cleavage of DNA Inhibition of bacterial Topoisomerase IV Mechanism is poorly understood. Fig: Mechanism of DNA Gyrase . 8

9. Fig: The bacterial cell & drug targets. 9

10. The drugs in this groups are : Nalidixic acid (1 st generation quinolon ) Highly protein bound. Mostly used in UTIs. B. Fluoroquinolones Modified 1 st generation quinolones. Not highly protein bound. Wide distribution to urine & other tissues. Has limited CSF penetration. Classification 10

11. Classification : By Generation Generation Drug names Spectrum 1 st Nalidixic acid Cinoxacin Gram negative; but, not pseudomonas species. 2 nd Norfloxacin Ciprofloxacin Enoxacin Ofloxacin Gram negative (including, pseudomonas species) Some Gram positive & some atypicals . 3 rd Levofloxacin Sparfloxacin Moxifloxacin Gemifloxacin Same as 2 nd generation with extended Gram positive & atypical coverage. 4 th Trovafloxacin Same as 3 rd generation with broad anaerobic coverage. 11

12. Summary of antimicrobial spectrum of quinolones 12

13. Resistance to quinolones may develop during therapy via mutations in the bacterial chromosomal genes encoding DNA gyrase or topoisomerase IV, or by active transport of the drug out of the bacteria. Mechanism of resistance to Quinolones 13

14. Pharmacokinetics of Quinolones Agent Administration Absorption Half-Life ( hrs ) Disposition Norfloxacin Oral 50% 4 (8 in anuria) M (20%)         R (27%) Ciprofloxacin Oral, IV 75% 4 (10 in anuria) R (50%) M Levofloxacin Oral, IV 98% 7 R (80%) Gatifloxacin Oral, IV 96% 7-8 R (70%) Moxifloxacin Oral, IV 89% 10-14 R (20%)         M (25%) (in liver) Nitrofurantoin Oral Adequate 0.6-1.2 R, M (in tissue) Polymyxin B Topical, oral, IV Not absorbed in adults; absorbed in children 6 by IV R 14

15. Indication Disease Recommendations RESPIRATORY TRACT INFECTIONS Pharyngitis , otitis media Not appropriate Necrotizing otitis Ciprofloxacin for Pseudomonas aeruginosa Sinusitis Third-generation fluoroquinolone Community-acquired pneumonia Third-generation fluoroquinolone Hospital- acquired pneumonia Ciprofloxacin, for susceptible gram-negative pathogens URINARY TRACT INFECTIONS Cystitis , uncomplicated All effective (second generation most appropriate) Pyelonephritis All effective (second generation most appropriate) Prostatitis All effective SKIN STRUCTURE INFECTIONS Primary cellulitis Not appropriate as first line therapy Anaerobic soft-tissue infections Not appropriate 15

16. Indication… Disease Recommendations OSTEOMYELITIS Gram-negative bacterial infections Ciprofloxacin Bacterial diarrheal diseases Ciprofloxacin used most commonly; all considered likely to be effective SEXUALLY TRANSMITTED DISEASES Gonorrhea Resistance testing required Chlamydia Ofloxacin, levofloxacin Chancroid All likely to be effective Mycoplasma Ofloxacin , levofloxacin Syphilis Not appropriate MYCOBACTERIAL DISEASES Disseminated M. avium complex Ciprofloxacin, ofloxacin as fourth agent if needed M. tuberculosis Ofloxacin , levofloxacin for drug-resistance or intolerance to first-line agents 16

17. The most common side effects are: Side effects Nausea Vomiting Diarrhea Headache Dizziness Insomnia 17

18. Adverse effects of Quinolones Liver toxicity is rarely for trovafloxacin . Photosensitivity occurs with lomefloxacin and pefloxacin . Fluoroquinolones may damage growing cartilage and cause an arthropathy . They are not used in patients under 18 years of age. The arthropathy is reversible. Since, fluoroquinolones are excreted in breast milk, they are contraindicated for nursing mothers. 18

19. available Pharmaceutical preparation of Quinolones in market… Nalidixic acid Nalid (Square): Powder for Suspn . 300mg/5ml Tk. 30.34/50ml; Tab. 5OOmg Tk. 4.06/Tab. Naligram (Acme): Susp 300mg/5ml, Tk. 56.64/100ml; Tk. 30.34/50ml; Tab. 5OOmg, Tk. 3.84/Tab. Nebactil ( Beximco ): Susp . 300mg/5ml, Tk.30.35/50ml Ultragram (Globe Pharma ): Susp . 300mg/5ml Tk.30/100ml; Tab., 500mg, Tk. 4/Tab. Utirex ( Opsonin ): Susp . 300mg/5ml, Tk.30/50ml 19

20. available Pharmaceutical preparation of Quinolones in market… Ciprofloxacin ( IV infusions, Ciprofloxacin as lactate.Oral preparation .Ciprofloxacin as hydrochloride) Aprocin ( Aristopharma ): Tab, 250mg, Tk.8/Tab;5OOmg, Tk.11.50/Tab; Susp , 250mg/5ml, Tk.60/60ml, Beuflox ( Incepta ): Susp , 250mm/5ml,Tk.60/60ml, Tk.80/100ml; Tab. 250mg,Tk.6/Tab; 500mg,Tk. 10/Tab; 750mg,Tk. 15/Tab., Ciprocin (Square ): Tab. 250mg ,Tk. 6/Tab;5OOmg.Tk 10/Tab; 750 mg. Tk. 15/Taka;Susp.250mg/5ml, Tk.80/100ml, 20

21. available Pharmaceutical preparation of Quinolones in market… Flontin ( Renata ): Tab. 250mg ,Tk. 6/Tab;5OOmg, Tk 3/Tab; 750 mg .Tk. 2.40/ Taka;Susp . 250mg/5ml, Tk.80/100ml, Floxabid (ACI): Susp 250mg/5ml, Tk.60/60ml;Tab. 5OOmg, Tk. 12/Tab; 250mg,Tk. 8/Tab;750mg Tk.18/Tab. Neofloxin ( Beximco ): Tab.5OOmg.Tk. 10/Tab;750mg, Tk. 1S./Tab; 250 mg.Tk . 6/Tab; Neofloxin XR ( Beximco ): Tab, 5OOmg,Tk.11/Tab. 21

22. available Pharmaceutical preparation of Quinolones in market… LEVOFLOXACIN Evo ( Beximco ): Tab. 250mg, Tk.5/Tab.;5OOmg, Tk.8/Tab . Leflox (ACI ): Tab. 5OOmg, Tk. 8/Tab Leo (Acme ): Tab. 250mg, Tk. 5/Tab.; 5OOmg,Tk. 8/Tab . Levoxln ( Incepta ): Tab. 250mg, Tk. 5/Tab.;5OOmg, Tk. 8/Tab. Trevox (Square ): Tab. 250mg, Tk.S /Tab.;5OOmg, Tk.8/Tab. Xenoxin ( Eskayef ): Tab. 250mg, Tk. 4/Tab.;500mg, Tk.7/Tab. 22

23. available Pharmaceutical preparation of Quinolones in market… Brand Name Manufacturer/Marketer Composition Dosage Form Pack Size & Price FACTICIN Square Pharmaceuticals Ltd. Gemifloxacin 320mg (as Gemifloxacin Mesylate INN) Tablet 6's: 390.00 MRP FLOGEM Opsonin Pharma Limited Gemifloxacin mesylate INN 320mg Film Coated Tablet 6's: 390.00 MRP GEMICIN 320 Healthcare Pharmacuticals Ltd. Gemifloxacin mesylate INN equivalent to Gemifloxacin 320mg tablet 7's MRP 455 Tk GEMINOX Eskayef Bangladesh Ltd Gemifloxacin mesylate INN 320mg Gemifloxacin mesylate INN equivalent to Gemifloxacin 320mg Film Coated Tablet 8's MRP: 520.00 23

24. available Pharmaceutical preparation of Quinolones in market… MOXIFLOXACIN Maximox (Orion ): Tab. 400mg, Tk.100/Tab . Odycin ( Beximco ): Tab. 400mg, Tk. 70/Tab; Eye drop 0.5% Optimox ( Aristopharma ): Tab. 400mg, Tk. 50/Tab. 24

25. The End 25

26. Do You Have Any Question.….. ? 26

27. Thank You For Your kind Attention 27