This document provides information about quinolones, including their classification, mechanism of action, and examples of specific quinolones. It discusses the classification of quinolones as first, second, third, or fourth generation. It also summarizes the mechanisms of action, pharmacokinetic properties, uses, and adverse effects of several common quinolones like ciprofloxacin, norfloxacin, ofloxacin, and moxifloxacin. Finally, it mentions some quinolones currently under clinical trials.

1. AVILEEN KAUR
ASSISTANT PROFESSOR
DEPT. OF PHARMACOLOGY
ISF COLLEGE OF PHARMACY
WEBSITE: - WWW.ISFCP.ORG
EMAIL: avileenkaurbrar@gmail.com
ISF College of Pharmacy, Moga
Ghal Kalan, nGT Road, Moga- 142001, Punjab, INDIA

2. QUINOLONES
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 Quinolones are synthetic antimicrobials having a quinolone
structure.
• Active against gram-ve bacteria, newer fluorinated compounds also inhibit
gram +ve bacteria.
• First member was nalidixic acid introduced in 1960’s
• Their usefulness is limited to urinary and GI tract infections because of
 Low potency
 Modest blood and tissue levels
 Limited spectrum
 High frequency of bacterial resistance

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 In gram negative bacteria –
•Inhibition of DNA gyrase enzyme (Inhibit negative super coiling)
 In gram positive bacteria –
•Inhibition of Topoisomerase IV – Inhibition of nicking and separation
of daughter DNA strands after DNA replication
•The malformed DNA is digested by Exoneucleases
Mechanism of Action

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ISF CP
CLASSIFICATION
Quinolones
NALIDIXIC ACID
Fluoroquinolones
New Generations
 Lomefloxacin
 Levofloxacin
 Prulifloxacin
 Sparfloxacin
 Gatifloxacin
 Gemifloxacin
 Moxifloxacin
 Trovafloxacin
 Alatrofloxacin
 Finafloxacin
Fluoroquinolones
First Generation
 Ciprofloxacin
 Norfloxacin
 Pefloxacin
 Ofloxacin
Second
Third
Fourth

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MOXIFLOXACIN
ALATROFLOXACIN
NORFLOXACIN
CIPROFLOXACIN
SPARFLOXACIN
PEFLOXACIN
PRULIFOXACIN
OFLOXACIN
TROVAFLOXACIN
GATIFLOXACIN
GEMIFLOXACIN
LOMEFLOXACIN
LEVOFLOXACIN

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•Gram negative, (Narrow spectrum)
•Bactericidal
•Acts by DNA gyrase inhibition
•Highly protein bound
• High concentration in urine
Adverse Effects
a) Neurological toxicity: (Vertigo, Visual disturbances , seizures and
Drowsiness)
b) Haemolysis in G-6PD deficiency
Uses
•Urinary antiseptic
•Bacterial Diarrhea
Nalidixic Acid

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Ciprofloxacin
•Most susceptible against aerobic Gram-ve bacilli
•Active against β-lactam and amino- glycoside resistant bacteria
•Long Post Antibiotic Effect (PAE)
•Less active at acidic pH
• Low frequency of mutational resistance
•Rapidly absorbed orally
Pharmacokinetics
• Interacts with food and calcium
•High tissue penetrability ( Except BBB)
•High conc. in urine and bile
First generation FQs

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Adverse Effects:
•CNS –Dizziness,Anxiety,Insomnia,Headache
•GIT-Nausea,Vomiting,Anorexia
•Tendonitis and tendon rupture
Uses:
•UTI
•Typhoid
•Tuberculosis
•Gonorrhoea

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Norfloxacin
• Less potent then ciprofloxacin
•Many pseudomonas and gram positive organisms are not
inhibited
•Attains lower concentration in tissues i.e non therapeutic
Uses
• UTI and GIT infections
• Bacterial diarrhoeas
*Not recommended for respiratory and other systemic infections.

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Ofloxacin
•Highly active against Mycobacterium leprae
•Also inhibits M.tuberculosis
•Alternative drug for nonspecific urethritis,cervicitis and atypical
pneumonia
•Lipid soluble,oral bioavailability is high
•Excreted unchanged in urine
Pefloxacin
•Methylated derivative of Norfloxacin,
•More lipid soluble, penetrates tissues better
•Oral bioavailability is 100%

12. 12Second Generation FQs
Lomeflaxacin
•More active against gram-negative bacteria and Chlamydia
•Once a day dose
Levofloxacin
•Levo-isomer of Ofloxacin,
•Oral absorption is 100%
•Single daily dose
•Minimal drug interactions

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Gatifloxacin
•Prolongs Q-T interval,
•Unexpected Hypo or Hyperglycemia in Diabetes mellitus patients. (
Withdrawn )
Moxifloxacin
•Most potent FQ against M. tuberculosis.
•Can prolong Q-T interval,
•Phototoxic

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 Nausea, vomiting & diarrhea
 Headache, dizziness, insomnia, skin rash
 Acute hepatitis & hepatic failure: trovafloxacin
 Photosensivity: lomefloxacin, pefloxacin
 QT prolongation: sparfloxacin
 Hyperglycemia or hypoglycemia
 May damage growing cartilage: arthropathy
 Tendinitis
Fluoroquinolones: adverse effects

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Drug Half-Life
(h)
Oral
Bioavailability
(%)
Peak Serum
Concentration
(mcg/mL)
Oral Dose
(mg)
Primary Route of
Excretion
Ciprofloxacin 3–5 70 2.4 500 Renal
Gatifloxacin 8 98 3.4 400 Renal
Gemifloxacin 8 70 1.6 320 Renal & nonrenal
Levofloxacin 5–7 95 5.7 500 Renal
Lomefloxacin 8 95 2.8 400 Renal
Moxifloxacin 9–10 > 85 3.1 400 Nonrenal
Norfloxacin 3.5–5 80 1.5 400 Renal
Ofloxacin 5–7 95 2.9 400 Renal
Pharmacokinetic Properties of Fluoroquinolones

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 NEMONOXACIN- has completed phaseii clinical trials in community-aquired
pneumonia and diabetic foot infections.
 FINAFLOXACIN- has proven activity against mrsa,vre and other drug-resistent
strains as well as anaerobes.
Oral and iv formulations of finafloxacin are undergoing phaseii clinical trials.
 DELAFLOXACIN- developed as an oral and iv formulation and being evaluated in
skin and soft tissue infections and community aquired pneumonia and bronchitis.
 ZABOFLOXACIN- undergoing phaseii trials for oral treatment of community aquired
pneumonia.
QUNOLONES UNDER CLINICAL TRIALS