Quinolones

Question 1

What are flouroquinolones ( Quinolones ) ?

Answer 1

1) Nalidixic acid
2) Ciprofloxacin
3) Levofloxacin
4) Moxifloxacin
5) Norfloxacin
6) Ofloxacin

Question 2

MOA for flouroquinolones ?

Answer 2

Inhibition of ligation step in bacterial DNA gyrase and bacterial topoisomerase 4

Question 3

Inhibition of bacterial DNA gyrase :

Answer 3

• Occurs more in Gram Negative Bacteria
• Causes increasing the number of permanent chromosomal breaks

Question 4

Inhibition of topoisomerase 4 :

Answer 4

-Occurs more in gram positive bacteria
-Causes interference with the separation of newly replicated DNA

Question 5

Antibacterial Spectrum of Quinolones :

Answer 5

• Bactericidal against :
  1) Gram positive bacteria ( Strep )
  2) Gram negative bacteria ( E.coli & Pseudomonas )
  3) atypical
  4) Mycobacteria

Question 6

Flouroquinolones are ……………………………… anti-biotic.

Answer 6

time - dependant killing

Question 7

Generations of Quinolones :

Answer 7

1) First - Generation
2) Second - Generation
3) Third - Generation
4) Fourth - generation

Question 8

First - generation quinolones :

Answer 8

1) Non-flourinated
2) Narrow Spectrum

3) Example : Nalidixic Acid

Question 9

Second-Generation flouroquinolones :

Answer 9

1) A: Gram-negative bacteria ( pseudomonas and H.influenzae ) B:atypical bacteria

2) Examples : Ciprofloxacin and Norfloxacin

Question 10

Third generation of flouroquinolones :

Answer 10

1) Gram negative bacteria , atypical and gram positive bacteria ( S.pneumonia and MSSA )

2) Example : Levofloxacin

Question 11

Fourth- Generation of flouroquinolones :

Answer 11

1) Gram negative enterobacteriaceae and gram positive ( Strep and staph )

2) Examples : Moxifloxacin , gemifloxacin and delafloxacin

Question 12

Clinically useful flouroquinolones :

Answer 12

1) Ciprofloxacin
2) Levofloxacin
3) Moxifloxacin

Question 13

Clinical usage of Ciprofloxacin :

Answer 13

1) traveler’s diarrhoea ( Gastroenteritis)
2) typhoid fever
3) Anthrax
4) UTIs ( مهمة )

Question 14

Pseudomonas and Ciprofloxacin :

Answer 14

Ciprofloxacin is effective against gram negative bacteria including P. Aeruginosa
And in case of pseudomonal infections , high dose of Ciprofloxacin is required

Question 15

Clinical Usage of Levofloxacin :

Answer 15

It has the same activity of Ciprofloxacin , in addition to the first-line therapy for community acquired-pneumonia

Question 16

Levofloxacin anti-microbial spectrum :

Answer 16

1) effective against gram negative bacteria including ( P.aeruginosa )
2) effective against gram positive bacteria ( Streptococcus not staphylococcus )
3) excellent activity against streptococcus pneumoniae

Question 17

Clinical Usage of Moxifloxacin :

Answer 17

1) effective against community acquired pneumonia but not nosocomial pneumonia

2) Second-line for TB

Question 18

Moxifloxacin antimicrobial Spectrum :

Answer 18

1) effective against S.pneumonia , gram negative bacteria and mycobacteria

2) Weak against pseudomonas

Question 19

Clinical utilisation of flouroquinolones :

Answer 19

1) Anthrax
2) Anerobic infections
3) Resistance respiratory infections
4) Gastrointestinal tract infections
5) Urinary tract infections

Question 20

Flouroquinolones and UTIs :

Answer 20

1) first-line oral therapy in Complicated cystitis
2) Second-line therapy in acute uncomplicated cystitis

Question 21

Different usage of flouroquinolones in UTIs is due to :

Answer 21

Have a propensity for causing collateral damage

Question 22

What are the flouroquinolones that are used as a second-agent in UTIs therapy :

Answer 22

Ciprofloxacin , Levofloxacin and Ofloxacin

Question 23

MOR of flouroquinolones: (Mainly and detailed)

Answer 23

1) Mainly : Chromosomal Mutations in topoisomerases 4
2) Detailed :
- Altered target
-Decreased accumulation
-Flouroquinolones degradation
-Cross resistance

Question 24

Bacteria and altered target in Flouroquinolones Resistance :

Answer 24

Mutations in gyrA or parC

Question 25

Decreased accumulation as a MOR in flouroquinolones:

Answer 25

1) Changing membrane permeability by porin channels
2) Efflux pump

Question 26

Administration and Absorption of flouroquinolones:

Answer 26

1) Mainly Oral , and for Ciprofloxacin and Levofloxacin by IV and ophthalmic preps

2) food , Ca++ , Al+++ and Mg++ interfere with absorption

Question 27

Distribution of flouroquinolones:

Answer 27

1) Very well distributed in tissues ( High concentration in bone , urine and lung )
2) Concentrate in Macrophages and neutrophils
3) Good CSF distribution

Question 28

Elemination of flouroquinolones:

Answer 28

• Most of them are excreted renally
• Moxifloxacin is excreted by liver

Question 29

The flouroquinolone that can be used in patients with renal impairment:

Answer 29

Moxifloxacin

Question 30

Adverse effects of Quninolones :

Answer 30

1) N,V,D
2) headache and dizziness
3) Peripheral neuropathy and glucose dysregulation
4) Phototoxicity
5) Articular cartilages erosion , tendinitis and tendon rupture
6) QT prolongation
7) drug-drug interaction

Question 31

Drug-drug interaction :

Answer 31

Ciprofloxacin inhibits cytochrome 450 metabolic pathway , then Serum concentrations of warfarin ,theophylline and cyclosporine increase