The document summarizes the quinolones, a class of antibiotics. It describes the history and generations of quinolones from the first discovered nalidixic acid to newer fourth generation drugs. Key points covered include the antimicrobial spectrum against both gram-positive and gram-negative bacteria, mechanisms of action and resistance, pharmacokinetics, individual drug properties, therapeutic uses, and adverse effects. Common side effects involve the gastrointestinal and neurological systems, and drug interactions can increase risks.

1. The
Quinolones
DR. J.N CHATURVEDI
ASSOC. PROF. (DESIG.), PHARMACOLOGY
S.S. MEDICAL COLLEGE, REWA (M.P)

2. HISTORY
The first quinolone- Nalidixic Acid was isolated in 1962 by George lesher as a byproduct of
synthesis of chloroquine.
It was made available for treatment of UTIs.
Norfloxacin was first fluoroquinolone approved in 1983 for medical use.

3. The Fluoroquinolones- Classification
Generation Agents Antimicrobial Properties
1st Generation (quinolones) Nalidixic acid Activity against aerobic, gram-
negative bacteria
2nd Generation Norfloxacin, Ciprofloxacin, Ofloxacin,
Levofloxacin, Lomefloxacin, and
Pefloxacin,
Activity against aerobic, gram-
negative as well as gram-positive
bacteria
3rd Generation Grepafloxacin, Gatifloxacin**,
Sparfloxacin, Temafloxacin, Tosufloxacin
and Pazufloxacin
Similar to 2nd generation with
greater potency against
pneumococci and additional
antianerobic activity
4th Generation Trovafloxacin, Clinafloxacin,
Moxifloxacin and Gemifloxacin
Similar to 3rd generation but more
potent.
**Systemic form

4. List of banned fluroquinolones
S.No Fluroquinolone Reason for ban
1. Lomefloxacin & sparfloxacin Phototoxicity & QT prolongation
2. Gatifloxacin (systemic form) Dysglycemia
3. Temafloxacin AIHA
4. Trovafloxacin Hepatotoxicity
5. Grepafloxacin Cardiotoxicity
6. Clinafloxacin Phototoxicity

5. The Quinolones- Mechanism of Action
Inhibits DNA gyrase (gr -ve bacteria) & Topoisomerase IV (gr +ve bacteria).
Interference with DNA replication.
Cell death

6. The Quinolones-Antibacterial Spectrum
Fluroquinolones are bactericidal against:-
◦ Enterobacteriaceae
◦ Pseudomonas spp. (Ciprofloxacin & Levofloxacin).
◦ Streptococci (newer generations.)
◦ Intracellular pathogens-Chlamydia, Mycoplasma, Mycobacteria.

7. The Quinolones- Mechanism of Resistance
Mutation in gene encoding DNA gyrase or Topoisomerase IV.
Active efflux of drug.
Production of Topoisomerase IV protecting proteins.

8. The Quinolones- Pharmacokinetics
Absorption-
◦ Well absorbed after oral administration.
◦ Tmax (oral)- 1 to 3 hrs.
Distribution-
◦ Widely distributed, large volume of distribution.
Metabolism-
◦ Metabolised in liver.
Excretion-
◦ All active/metabolites are excreted in urine (except moxifloxacin)
Longest acting fluoroquinolone-
Sparfloxacin (T1/2= 19hrs)

9. The Quinolones- Pharmacological
Properties
Individual Agents
1. Norfloxacin:
◦ Good Gr-ve activity. (Enterobacteriaceae)
◦ Low serum level as compared to ciprofloxacin.
◦ Dose= 400 mg PO q12h.
2. Ciprofloxacin:
◦ Good oral bioavailability (70%).
◦ Can be used by oral & i.v. route.
◦ Typical Dosing= 250-750 mg i.v & 250-500 mg PO twice daily.(max. 1.5g/d)

10. The Quinolones- Pharmacological
Properties
Individual Agents
3. Ofloxacin/Levofloxacin:
◦ Ofloxacin has additional activity against Gram +ve bacteria.
◦ L-isomer (Levofloxacin) has still better activity against strep.
◦ Excellent oral bioavailability. Thus both oral & i.v. dose are same.
◦ Typical dosing:
◦ Levofloxacin 250-750 mg once daily.
◦ Ofloxacin 100-200 mg twice daily

11. The Quinolones- Pharmacological
Properties
Individual Agents
4. Moxifloxacin:
◦ Has further improved activity against gr +ve bacteria. (S.pneumoniae)
◦ Also active against anaerobes. (B.fragilis)
◦ Excellent oral bioavailability. Thus, both oral & i.v. dose are same.
◦ Metabolized in liver and excreted in bile
◦ Not excreted in urine thus not suitable for UTIs.
◦ T1/2= 12hrs
◦ Typical dosing- 400 mg once a day

12. The Quinolones- Pharmacological
Properties
Individual Agents
5. Gatifloxacin/ Gemifloxacin
◦ Antimicrobial spectrum similar to moxifloxacin.
◦ Enhanced potency against Gr+ve
◦ Less active against B.fragilis.
◦ Gatifloxacin no longer used for systemic purpose but ophthalmic preparations are used.
◦ Typical dosing- Gemifloxacin 320 mg once a day

13. The Quinolones- Therapeutic Uses
1. Urinary Tract Infections:
◦ Fluroquinolones are mainstay therapy for both Upper & Lower UTIs.
◦ More efficacious than TMP-SMX & oral β-lactam.
◦ All except Moxifloxacin.
◦ Typical duration of therapy for uncomplicated cystitis is 3 days & 5-7 days for uncomplicated
pyelonephritis.
2. Prostatitis:
◦ Norfloxacin/ Ciprofloxacin/ Ofloxacin/ Levofloxacin used for patients not responding to TMP-SMX.
◦ Duration of therapy 4-6 weeks.

14. The Quinolones- Therapeutic Uses
3. Sexually Transmitted Diseases:
◦ Chlamydia urethritis/ cervicitis: Alternative to Azithromycin/ Doxycycline. 7 day therapy with
ofloxacin/levofloxacin.
◦ Chancroid (H.ducreyi): Alternative to Azithromycin. 3 day therapy with Ciprofloxacin.
4. GI & Abdominal infections:
◦ Traveler's Diarrhea: 1-3 day therapy with Norfloxacin/Ofloxacin/levofloxacin/Ciprofloxacin for
treatment. Ciprofloxacin single daily dose for prophylaxis.
◦ Enteric fever: Ciprofloxacin/ Ofloxacin.
◦ Intra-abdominal infections: Ciprofloxacin/Ofloxacin/Levofloxacin + Metronidazole. Moxifloxacin as
single agent is comparable to piperacillin + tazobactam for complicated intra-abdominal infections.

15. The Quinolones- Therapeutic Uses
5. Respiratory Tract infections:
◦ Community Acquired pneumonia
◦ Upper respiratory tract infections
◦ Mild to Moderate respiratory exacerbations in pts with cystic fibrosis.
6. Bone, Joint & Soft tissue Infections:
◦ Chronic osteomyelitis : Ciprofloxacin + Rifampicin
◦ Diabetic foot: Fluroquinolones (parenteral) + Metronidazole.
Levofloxacin/ Moxifloxacin/
Gemifloxacin.

16. The Quinolones- Therapeutic Uses
7. Other infections:
◦ Ciprofloxacin/ levofloxacin for prophylaxis of Anthrax & t/t of Tularemia.
◦ Moxifloxacin for MDR TB, atypical mycobacterial infections & MAC.
◦ Ciprofloxacin/ levofloxacin for prophylaxis & treatment of plague.

17. The Quinolones- Adverse Drug Reactions
1. Gastrointestinal:
◦ Common (3%-17%)
◦ Nausea, vomiting, abdominal discomfort.
◦ Common Cause of C.difficile colitis.
2. Neurological:
◦ Less common (1%-11%).
◦ Mild headache, dizziness are more common.
◦ Rarely neuropsychiatric reactions s/a hallucinations, delirium & seizures.
◦ Seizures particularly occurs in patients on theophylline or NSAIDs.

18. The Quinolones- Adverse Drug Reactions
3. Musculoskeletal:
◦ Arthralgia, joint pain.
◦ Tendon rupture (usually of Achilles tendon) in elderly or pts. On corticosteroids.
◦ Cartilage damage (in animal studies not in humans) Typically avoided in pregnancy & children <8
years
4. Other:
◦ Moxifloxacin: QT prolongation.

19. The Quinolones- Drug Interactions
1. Ca/Fe/Al preparations & All quinolones: Inhibits absorption of quinolones.
2. Methylxanthines & Ciprofloxacin: Increased toxicity of methylxanthine.
3. NSAIDS & quinolones: Increased risk of seizures.
4. Class III & Class IA antiarrhythmics + quinolones: Increased chances of QT prolongation &
Torsade-de-pointes.