Mechanism of action dNa gyrase Stabilize Break Reseal break positive node back segment on front side topOisomerase Key enzymes in DNA replication; bacterial DNA is supercoiled
Mechanism of action Topoisomerase DNA gyrase Key enzymes in DNA replication: bacterial DNA is supercoiled
Mechanism of action porin DNA gyrase opo somerase Gram(-) Gram(+)
Mechanism of action Topo isomerase DNA gyrase Gram (-) Gram (+) porin
Mechanism of action dna gyrase Catalytic subunit m八 Fluoroquinolones ATP AtP 4 stacked molecules DNA gyrase aTP binding subunit
Mechanism of action Fluoroquinolones: 4 stacked molecules DNA gyrase Catalytic subunite DNA gyrase ATP binding subunite
Mechanism of resistance decreased permeability active efflux system porin DNA gyrase op mutation of Isomerase the enzymes Gram(-) Gram(+)
Mechanism of resistance Topo isomerase DNA gyrase Gram (-) Gram (+) porin mutation of the enzymes active efflux system decreased permeability
ADME of fluoroquinolones Absorption: well absorbed bound by divalent cations Do not administer with iron magnesium, calcium Distribution: all distribute widely(even in CSF), and most concentrate in urine Metabolism: hepatic metabolism diminishes the activity of norfloxacin and ciprofloxacin Several have predominately hepatic clearance (Grepafloxacin, Sparfloxacin, Trovafloxacin EXcretion: urinary excretion predominates for the first generation fluoroquinolones
• Absorption: well absorbed; bound by divalent cations – Do not administer with iron, magnesium, calcium • Distribution: all distribute widely (even in CSF), and most concentrate in urine • Metabolism: – hepatic metabolism diminishes the activity of norfloxacin and ciprofloxacin – Several have predominately hepatic clearance (Grepafloxacin, Sparfloxacin, Trovafloxacin) • Excretion: urinary excretion predominates for the first generation fluoroquinolones ADME of fluoroquinolones