1. Antimicrobial Agents (Sulfonamides and Quinolones)
Prof. R. K. Dixit
Pharmacology and Therapeutics
K.G.M.U. Lucknow

2. Objectives After completion of this lecture you will be able to
Know about sulphonamides
Types (Classification)
MOA
Combination with Trimethoprim or Pyrimethamine
Uses
ADRs, DDI, and Contraindications
Special points
Know about Quinolones

3. Quinolones and Fluoroquinolones
Have Quinolone structure
Nalidixic acid is first member
Fluorination of Quinolones Fluoroquinolones
Gram negative mainly
(Plus gram positive New FQs)
N to P

4. Why not human cells affected ? Mammalian cells have Topoiosmerase II
MOA- (Queen stops gyrating dancers)
In gram negative –
Inhibition of DNA gyrase enzyme (Inhibit negative super coiling)
In gram positive –
Inhibition of Topoiosmerase IV – Inhibition of nicking and separation of daughter DNA strands after DNA replication (Inhibition of Decatenation)
The malformed DNA is digested by Exonucleases
Why not human cells affected ?
Mammalian cells have Topoiosmerase II

5. Quinolones

10. Resistance- Due to mutation in chromosomes
Altered DNA gyrase and Topoisomerase IV
Reduced permeability for drug
Increased efflux of drug

11. Members MAN Can SPOT Good Life Fluoroquinolones Fluoroquinolones
Nalidixic acid
Fluoroquinolones
New Generations
Lomefloxacin
Levofloxacin
Prulifoxacin
Sparfloxacin
Gatifloxacin
Gemifloxacin
Moxifloxacin
Trovafloxacin
Alatrofloxacin
Finafloxacin
Fluoroquinolones
First Generation
Ciprofloxacin
Norfloxacin
Pefloxacin
Ofloxacin
Second
Third
Fourth
MAN Can SPOT Good Life

12. M A N Can S P O T Good Life Moxifloxacin Alatrofloxacin Norfloxacin
Ciprofloxacin
Sparfloxacin
Pefloxacin
Prulifoxacin
Ofloxacin
Trovafloxacin
Gatifloxacin
Gemifloxacin
Lomefloxacin
Levofloxacin M A N
Can S P O T
Good
Life

13. Don’t give with Nitrofurantoin (Antagonism)
Nalidixic Acid-
Gram negative, (Narrow spectrum)
Bactericidal,
Acts by DNA gyrase inhibition,
Highly protein bound,
High concentration is in Urine
Neurological toxicity(vertigo, visual and seizures)
Haemolysis in G-6PD deficiency
Used as
Urinary antiseptic,
Bacterial Diarrhea.
Don’t give with Nitrofurantoin (Antagonism)

14. First generation FQs Ciprofloxacin- Drug Interaction-
Long Post Antibiotic Effect (PAE)
Less active at acidic pH
Interacts with food and calcium
High tissue penetrability ( Except BBB)
High conc. in urine and bile
CNS side effects are common,
Tendonitis and tendon rupture
Drug Interaction-
Inhibition of metabolism of other drug,
Chelation
QT interval prolongation

15. USES- (Extended spectrum)
CNSI, MFI, OI, ENTI, RTI, GITI, UTI, PID, STDs, SBI
Nosocomial Infections
Septicaemia
Tuberculosis- MDR TB and XDR TB
Typhoid
Treatment 2 weeks
Prevention of carrier state 2 months
Other drugs-
Other FQs
Cephalosporins ,Ceftriaxone (Fastest)
Chloramphenicol
Cotrimoxazole
Ampicillin

16. Norfloxacin – Ofloxacin- Pefloxacin – Less potent,
Primarily used for UTI and GIT infections,
Ofloxacin-
Highly active against Mycobacterium leprae
Pefloxacin –
Methylated derivative of Norfloxacin,
Oral bioavailability is 100%

17. Second Generation FQs Lomefloxacin – Levofloxacin –
Once a day dose
Levofloxacin –
Levo-isomer of Ofloxacin,
Oral absorption is 100%
Single daily dose
Minimal drug interactions

18. Sparfloxacin – Enhanced action against Chlamydia,
Maximum half life and Plasma Protein Binding
Second line Anti-tubercular drug
MAC in AIDS, Leprosy
No interaction with Theophylline and Warfarin,
Photoxicity
Single daily dose,
May prolong Q-T interval ( Avoid with Cisapride, TCAs, Phenothiazines, Anti-arrhythemics, Hypokalemia)

19. Gatifloxacin – Moxifloxacin – 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
Trovafloxacin –
Hepatotoxic (Reserved and maximum of 15 days Tt.)
Alatrofloxacin - Prodrug of Trovafloxacin
Finafloxacin, Prulifoxacin, Gemifloxacin

20. Elimination of Fluoroquinolones
Renal
Norfloxacin
Ofloxacin
Ciprofloxacin
Lomefloxacin
Levofloxacin
Gatifloxacin
Hepatic
Pefloxacin
Moxifloxacin
Trovafloxacin
Sparfloxacin
Gemifloxacin
Fluoroquinolones safe in renal failure Pefloxacin Moxifloxacin Trovafloxacin

21. Miscellaneous points about Quinolones
No FQs effective against spirochaetes
Ofloxacin and Pefloxacin are effective against M. leprae
Moxifloxacin is the only FQ NOT used in UTI as its concentration is poor in urine

22. Levofloxacin, Moxifloxacin, Gemifloxacin,
Levofloxacin, Moxifloxacin, Gemifloxacin, Gatifloxacin, Sparfloxacin have good activity against S. pneumonia and also called Respiratory FQs. They also have good activity against anaerobes
Chronic Prostatitis Tt. Ciprofloxacin for 1 to 2 months
Gonorrhea- Tt. Single dose Ciprofloxacin 500mg
Chlamydia trachomatis- Ciprofloxacin one week or single dose Azithromycin

23. Summary Sulphonamides Quinolones
Act by inhibition of folic acid synthesis
Combined with Trimethoprim
Produce Stevens Johnson Syndrome
Prolonged use may produce hypothyroidism, goitre, arthritis and drug fever
Quinolones
Act by inhibition of DNA gyrase or Topoiosmerase IV
Have extended spectrum
Have chelating and enzyme inhibition property
Used for multiple infective diseases

24. Thanks