Nucleic Acid Synthesis Inhibitors

Mechanism Of Action??☆☆☆

Following cell wall entry through porin channels, fluoroquinolones bind to these enzymes and interfere with DNA ligation. This interference increases the number of permanent chromosomal breaks, triggering cell lysis.

Gram negative-DNA gyrase

Gram positive-topoisomerase IV

First generation?

Nalidixic acid [with each generation become wider spectrum]

Second generation

Ciprofloxacin

Third generation

Levofloxacin

Fourth generation☆☆☆

-Moxifloaxacin

-Gemifloxacin

-Delafloxacin

Resistance

1)Altered target binding:Mutations in bacterial genes encoding DNA gyrase or topoisomerase IV alter target site structure amd reduce binding efficiency of fluoroquinolones.

2) Decreased accumulation: Reduced intracellular concentration is linked to

1-a reduction in membrane permeability or

2- efflux pumps

Alterations membrane permeability are mediated through a reduction in outer membrane porin proteins, thus limiting drug access to topoisomerases. Efflux pumps actively remove fluoroquinolones from the cell.

3)Fluoroquinolone degradation: An aminoglycoside acetyltransferase variant can acetylate fluoroquinolones, rendering them inactive.

Adverse reactions?

Tendinitis, tendon rupture, peripheral neuropathy, and central nervous system effects.

Should be avoided in patients predisposed to arrhytmias or taking medication associated with QT prolongation. Ciprofloxacin inhibits P450.