Dr. RAGHU PRASADA M SMBBS,MDASSISTANT PROFESSOR DEPT. OF PHARMACOLOGYSSIMS & RC.

1

The quinolones (Qs) and fluoroquinolones (FQs)are a family of broad-spectrumsynthetic antimicrobial agents.

The parent of the group is nalidixic acid The fluoroquinolones have a fluorogroup attached the central ring system.

Qs and FQs are bactericidal drugs.

FQs enter into the host cells active against intracellular pathogens Legionella spp., Mycoplasma spp. and Chlamydia spp.

They inhibit enzymes called topoisomerase, enzymes needed for supercoiling, replication and separation of circular bacterial DNA.

1. G-VEDNA Gyrase is a topoisomerase II that catalyzes the negative supercoiling of the circular DNA found in bacteriaprevent replication of bacterial DNA

2. G+veTopoisomerase IV relaxation of the supercoiled circular DNA, enabling the separation of the interlinked daughter chromosomes at the end of bacterial DNA replicationinhibition of cell division

First Generantion- Norfloxacin, Ciprofloxacin, Ofloxacin, Pefloxacin, Lomefloxacin

Second Generation- Levofloxacin, Prulifloxacin, Third Generation- Gatifloxacin, Sparfloxacin,

Gemifloxacin Fourth Generation- Moxifloxacin, Trovafloxacin,

Alatrofloxacin, Finafloxacin

CIPROFLOXACIN The most potent of the fluoroquinolones for P.

aeruginosa. Long post-antibiotic effect. Well absorbed from GIT. Administration: orally, IV. Excreted in urine. Potent CYP450 inhibitor

CIPROFLOXACIN The most potent of the fluoroquinolones for P.

aeruginosa. Long post-antibiotic effect. Well absorbed from GIT. Administration: orally, IV. Excreted in urine. Potent CYP450 inhibitor

Levofloxacin An isomer of Ofloxacin and has largely replaced it

clinically. Very well absorbed from GIT. Administration: orally, iv. Excreted unchanged Long post-antibiotic effects. Long-acting (single daily dose)

Treatment respiratory tract infections due to S. pneumonia (pneumonia, COPD exacerbation).

Used in the treatment of prostitis due to E. coli and of sexually transmitted diseases(gonorrhea), with the exception of syphilis.

levofloxacin is utilized in wide range of infections, including skin infections, acute sinusitis, nosocomial pneumonia

MOXIFLOXACIN Long-acting (single daily dose). Long post-antibiotic effect. Mostly used for the treatment respiratory tract

infections (pneumonia, COPD exacerbation). Used for the treatment severe bacterial infections

including sepsis, peritonitis. The most potent fluoroquinolones against M.

tuberculosis. Poor activity against P. aeruginosa.

FINAFLOXACINNovel, under phase IIIAntibacterial activity increases at acidic pHMore efficacious in tissue and body compartments

acidified due to infection and inflammationWidest spectrum of G+ve, G-ve, anaerobic, and

atypical pathogensVery long t1/2

High safety profile-no incidence of hepato, renal, cardio and phototoxicity.

GI: Nausea, vomiting

CNS: HA, dizziness, confusion, insomnia, delerium, hallucinations, seizure (rare)

Cardiovascular: QT-prolongation Torsades de pointes (III gen)

Endocrine -Blood glucose disturbances in DM patients(levo, moxi)

Musculoskeletal: Rupture of tendon (prolonged use)

Hepatotoxicity- Trova, Alatro

Photo toxicity- Lome, Pefl, Gati,

Ciprofloxacin is a potent CYP450 inhibitor. Increases plasma levels and toxic effects of anticoagulants, digoxin, theophylline

FQs in combination with with class IA and class III antiarrhythmics prolong QT and may cause arrhythmias

Antacids has been found to result in six to ten fold decreases in the absorption of oral quinolones.

Fluoroquinolones generally should not be administered to patients younger than 18 years of age.

Fluoroquinolones should not be administerd to pregnant or lactating women.

Should not be given to arrythmic patient.

Gemifloxacin has been approved for the treatment of mild to moderate community-acquired pneumonia and acute exacerbation of chronic bronchitis but has increased risk of tendinitis

Sparfloxacin-photosensitivity, cardiotoxicity- QTcprolongation

Trovafloxacin/Alatrofloxacin-was withdrawn because of the risk of hepatic toxicity.

Gatifloxacin was withdrawn because of an increased frequency of hypoglycemia and hyperglycemia, cardiotoxicity- QTc prolongation

NALIDIXIC ACID Non flourinated quinolone 98% protein bound, excre- urine G-ve coliforms except pseudomonas

PHENAZOPYRIDINEDye with analgesic effectsRelives burning sensation, dysuria, urgencyADR-Epigastric distress, orange coloured urine

Nitrofurantoin niitroanion superoxidedamagebacterial DNA

Nitrofuron derivative MOA- blocks acetyl CoA synthesis carbohydrate

metabolism BacteriostaticBactericidal Loses its action at p H of 8 E.coli, proteus, St.aureus, E.faecalis Prophylaxis of UTI ADR-Nausea, Ph.neuritis, hepatitis, pulmonary

fibrosis, hemolytic anemia D/I- probenacid, nalidixic acid

Acidic urine NITROFURANTOIN TETRACYCLINE METHICILLLIN CLOXACILLIN

Alkaline urine COTRIMOXAZOLE GENTAMYCIN CEPHALOSPORINS