1

Quinolones

Welcome to a Presentationon

2

Presented By:Group : 4

Bipasha Belal (121033)Protic Jodder (121031)MD. Sabbir Hossain (121026)Bikash Kumar Ghosh (121016)

3rd Year; 1st SemesterDepartment of PharmacyJessore University of Science & Technology

Presented To:MD. Rafiqul IslamLecturerDepartment of PharmacyJessore University of Science & Technology

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.

4

History

o A group of synthetic antibacterial agents mainly effective against G-ve.

o Nalidixic acid first member introduced in 1964 for urinary and GIT infections.

o Its congeners Oxolinic acid and rosoxacin with more potency in 1970s.

o Second generation called fluoroquinolones with extended spectrum and systemic effects in 1980s.

o Since then many synthesized with useful spectrum.

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

6

Quinolones : Chemistry…

Fig: Essential structure of all quinolone

7

8

Mechanism of Action Quinolones have dual MOA:

1. Inhibition of bacterial DNA Gyrase (Topoisomerase II) Formation of quinolone-DNA-Gyrase complex Induced cleavage of DNA

2. Inhibition of bacterial Topoisomerase IV Mechanism is poorly understood.

Fig: Mechanism of DNA Gyrase.

9

Fig: The bacterial cell & drug targets.

10

→The drugs in this groups are :A. Nalidixic acid (1st generation quinolon)

Highly protein bound. Mostly used in UTIs.

B. Fluoroquinolones

Modified 1st generation quinolones. Not highly protein bound. Wide distribution to urine & other tissues. Has limited CSF penetration.

Classification

11

Classification : By GenerationGeneration Drug names Spectrum1st Nalidixic acid

CinoxacinGram negative; but, not pseudomonas species.

2nd NorfloxacinCiprofloxacinEnoxacinOfloxacin

Gram negative (including, pseudomonas species)Some Gram positive & some atypicals.

3rd LevofloxacinSparfloxacinMoxifloxacinGemifloxacin

Same as 2nd generation with extended Gram positive & atypical coverage.

4th Trovafloxacin Same as 3rd generation with broad anaerobic coverage.

12Summary of antimicrobial spectrum of quinolones

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

14

Pharmacokinetics of QuinolonesAgent 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%) MLevofloxacin 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

15

IndicationDisease Recommendations

RESPIRATORY TRACT INFECTIONSPharyngitis, otitis media Not appropriateNecrotizing otitis Ciprofloxacin for Pseudomonas aeruginosa

Sinusitis Third-generation fluoroquinoloneCommunity-acquired pneumonia Third-generation fluoroquinoloneHospital-acquired pneumonia Ciprofloxacin, for susceptible gram-negative

pathogensURINARY TRACT INFECTIONS

Cystitis, uncomplicated All effective (second generation most appropriate)

Pyelonephritis All effective (second generation most appropriate)

Prostatitis All effectiveSKIN STRUCTURE INFECTIONS

Primary cellulitis Not appropriate as first line therapyAnaerobic soft-tissue infections Not appropriate

16

Indication…Disease Recommendations

OSTEOMYELITISGram-negative bacterial infections CiprofloxacinBacterial diarrheal diseases Ciprofloxacin used most commonly; all considered

likely to be effective

SEXUALLY TRANSMITTED DISEASESGonorrhea Resistance testing requiredChlamydia Ofloxacin, levofloxacinChancroid All likely to be effectiveMycoplasma Ofloxacin, levofloxacinSyphilis Not appropriate

MYCOBACTERIAL DISEASESDisseminated M. avium complex Ciprofloxacin, ofloxacin as fourth agent if needed

M. tuberculosis Ofloxacin, levofloxacin for drug-resistance or intolerance to first-line agents

17

The most common side effects are:

Side effects

• Nausea• Vomiting• Diarrhea• Headache• Dizziness• Insomnia

18

Adverse effects of Quinolones

① Liver toxicity is rarely for trovafloxacin.② Photosensitivity occurs with lomefloxacin and

pefloxacin.③ 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.

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

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,

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.

22

available Pharmaceutical preparation of Quinolones in market…

LEVOFLOXACINEvo (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.

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

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.

25

The End

26

DoYouHave AnyQuestion.…..?

27

Thank YouFor

Your kind Attention