Quinolones & Metronidazole

Question 1

Fluoroquinolones is bacteriostatic or bactericidal?

Answer 1

Bactericidal

Question 2

MOA of quinolones

Answer 2

Fluoroquinolones enter bacteria through porin channel & exhibit antimicrobial effects on DNA gyrase (topoisomerase II) & bacterial topoisomerase IV

Gram negative bacteria
Exp: P. Aeruginosa
-inhibit bacteria enzyme DNA gyrase (topoisomerase II)
-thus, inhibit DNA replication

Gram positive bacteria
Exp: streptococcus pneumoniae
-inhibit topoisomerase IV
-interfere with separation of replicated chromosomal DNA into respective daughter cells during cell division.

Question 3

Classification of fluoroquinolones

Answer 3

1. First generation
   Exp: Nalidixic acid
   -narrow spectrum of susceptible organism (moderate gram negative)
   -urinary tract infection
2. Second generation
   Exp: Ciprofloxacin, Norfloxacin
   -activity again aerobic gram negative bacteria and atypical bacteria: Mycobacterium pneumoniae & chlamydia pneumoniae
3. Third generation
   Exp: Levofloxacin
   -activity against gram positive bacteria
4. Fourth generation
   Exp: Moxifloxacin & Gatifloxacin
   -activity against anaerobic & gram positive bacteria

Question 4

Therapeutic indication for Norfloxacin, Ciprofloxacin, Levofloxacin & Moxifloxacin

Answer 4

Norfloxacin : Urinary tract infection

Ciprofloxacin : Traveler’s diarrhea by E. Coli, second line agent for tuberculosis, typhoid fever by salmonella typhi.

Levofloxacin & Moxifloxacin:

• respiratory infection by streptococcus pneumoniae
• postitis, skin infection, nosocomial pneumonia.

Question 5

Mechanism of resistance of quinolones

Answer 5

1. Altered target
   - chromosomal mutation in bacterial genes (gyr A & par c) reduce the affinity of fluoroquinolones at site of action.
   - both topoisomerase II and (DNA gyrase) & topoisomerase IV undergoes mutation.
2. Decreased accumulation
   - linked to porin channel & efflux pumps.

Question 6

Adverse reaction of fluoroquinolones

Answer 6

• Phototoxicity
• Nausea
• Vomitting
• headache
• Diarrhea

Question 7

Fluoroquinolones is contraindicated in?

Answer 7

• pregnant women with lactation

- children under 18 years old

Question 8

Metronidazole is a drug of choice for?

Answer 8

-pseudomembranous colitis caused by clostridium difficile (gram positive, anaerobic)

Question 9

MOA of metronidazole

Answer 9

• reduced cytotoxic form
• binds protein & DNA
• cell death

Question 10

Adverse effects of Metronidazole

Answer 10

• Nausea
• Vomitting
• Epigastric distress
• abdominal cramps
• if taken with alcohol, it can cause disulfiram-like reaction

Question 11

What is disulfiram-like reaction?

Answer 11

• Disulfiram blocks the oxidation of acetylaldehyde to acetic acid by inhibiting aldehyde dehydrogenase.
• this results in accumulation of the acetyldehyde in the blood, causing flushing, tachycardia, hyperventilation and Nausea.

Question 12

Therapeutic indication for metronidazole

Answer 12

• Amebiasis
• Giardiasis
• Trichomoniasis