Topic 14-Quinolones and Fluoroquinolones

Question 1

Mechanism of action of quinolones and fluoroquinolones?

Answer 1

Inhibition on bacterial DNA gyrase leading to DNA strand breakage (more important in gram positive bacteria)
and inhibition of bacterial topoisomerase IV inhibiting seperation of replicated DNA (important in gram negative bacteria)

Question 2

Are Quinolones and fluoroquinolones bactericidal or bacteriostatic? Time or concentration dependent?

Answer 2

Bactericidal and concentration dependent

Question 3

Non-flourinated quinolones

Answer 3

Nalidixic acid

Question 4

Pharmacokinetics of Nalidixic acid
Strong ABX?
Excretion?
Spectrum?
Adverse effects?
Indications?

Answer 4

Nalidixic acid is a weak antibiotics
Excreted in the kidneys making it good against UTIs
Spectrum is gram negative aerobic infections
Adverse effect: GI and CNS
Indications: used to be used in UTI

Question 5

Interactions of quinolones

Answer 5

Inhibitions of CYP1A2

Binds Ca, Al, Mg, Fe, Zn

Question 6

Contraindications of quinolones

Answer 6

Pregnancy, children under 18, allergy, epilepsy

Question 7

How many generations of fluoroquinolones are there and what is the base chemical?

Answer 7

4 generations with nalidixic acid as common precursor

Question 8

General pharmacokinetics of Fluoroquinolones
Bactericidal or bacteriostatic?
Spectrum?
Administration?
Distribution?
Elimination
Time/concentration/or other dependent killing

Answer 8

Bactericidal
Broad spectrum
High oral bioavailability (don't take with divalent cations)
Wide tissue distribution (not CNS)
Renal elimination
AUC/MIC-dependent killing

Question 9

Clinical use of Fluoroquinolones?

Answer 9

FILL in later

Question 10

Adverse effects of Fluoroquinolones

Answer 10

1. )Damage growing cartilage in children under 18
2. )Tendinitis
3. ) Pseudomembranous colitis
4. )Anxiety, insomnia, convulsions, psychotic state
5. )QT prolongation
6. )Can’t combine with anti-arrhythmics, can cause high potassium levels

Question 11

What is the 1st generation fluoroquinolones?

Answer 11

Norfloxacin

Question 12

Spectrum of Norfloxacin

Answer 12

Gram negative bacteria (E. Coli, K. pneumoniae, P. mirabilis, shigella, neisseria, H. influenzae)
No or limited activity against Pseudomona, gram-positive cocci, anaerobe, intracellular and atypical bacteria

Question 13

Pharmacokinetics of Norfloxacin
How is it used? Half life?
Administration

Answer 13

Low bioavailability systemically, renal excretion making it good for UTI
Half life is short
oral twice a day

Question 14

Clinical use of Norfloxacin

Answer 14

UTI and prostatitis

Question 15

Adverse effect of Norfloxacin

Answer 15

CI, CNS

Question 16

2nd generation fluoroquinolones?

Answer 16

Ciprofloxacin and ofloxacin

Question 17

Spectrum of ciprofloxacin and ofloxacin?

Answer 17

Excellent activity for gram negative aerobic bacteria
Good activity against gram positive cocci (MRSA?)
Legionella
Mycobacterium
Not effective against atypicals and anaerobes

Question 18

Ciprofloxacin is specifically used for which bacteria

Answer 18

B. Antracis and Pseudomonas

Question 19

Pharmacokinetics of Ciprofloxacin and Ofloxacin
Administration?
distribution?

Answer 19

Administered twice daily, can be parenteral or topical

High serum concentration

Question 20

Clinical use of ciprofloxacin and ofloxacin

Answer 20

-UTIs, multidrug resistant bacteria like pseudomonas
-bactertial diarrhea (shigella, salmonella, E. coli, campylobacter)
-soft tissue, bone, joint, and systemic infections (including sepsis)
-second line treatment in tuberculosis
Not effectie in pneumococci

Question 21

Adverse effects of ciprofloxacin and ofloxacin

Answer 21

GI, CNS, bone cartilage in adolescent, drug interactions

Question 22

What is the third generation fluoroquinolones

Answer 22

Levofloxacin

Question 23

Spectrum of Levofloxacin

Answer 23

Second group with better activity against gram positive bacteria (strep pneumonia) and atypical (mycoplasma) bacteria
Less activity with pseudomonas

Question 24

Clinical use of Levofloxacin

Answer 24

Upper and lower respiratory tract infections

Prostatitis, skin infections, nosocomial pneumonia

Question 25

Pharmacokinetics of Levofloxacin
Administration?
Distriubiton?

Answer 25

1-2x daily oral/IV

good absorption, high serum concentration

Question 26

Adverse effects of levofloxacin

Answer 26

GI, QT prolongation, phototoxicity

Question 27

Fourth generation of fluroroquinolones drugs

Answer 27

Moxifloxacin and prulifloxacin

Question 28

Spectrum of Moxifloxacin and Prulifloxacin

Answer 28

Similar to 3rd generation with further improved activity against gram positive (strep pneumonia)
Moxifloxacin has some activity against anaerobes
Intracellular pathogens

Question 29

Clinical use of Moxifloxacin and Prulifloxacin

Answer 29

Upper and lower respiratory tract infections, NOT UTI
(Community acquire and noscomial)
Mixed infection (aerobe and anaerobic)

Question 30

Pharmacokinetics of Moxifloxacin and Prulifloxacin
Administration
Absorption
Elimination

Answer 30

Once a day, long half life
good absortion
and low elimination

Question 31

Adverse effects of Moxifloxacin and Prulifloxacin

Answer 31

GI, CNS, and pseudomembranous colitis