Fluroquinolones

Question 1

General features

Answer 1

• antimicrobial
• double ring of quinoline
• uncommon SE in TD
• competitive inhibition of CYP3A and CYP1A
• rapidly inhibit DNA synthesis by promoting cleavage of bacterial DNA -> rapid bacterial death
• Bacteriocidal , CONCENTRATION dependant.
• PAE: 2-5h

Question 2

Spectrum

Answer 2

1st gen: not used anymore except for research. Nalidixic acid, oxalinic acid, cinoxacin
* Effective against Gram-ve. Enteric bacteria

2nd gen: 1-fluro: Flumequine(used in livestock) , Norfloxacin (topically) , mostly G- enteric bacteria. 2-fluro: Danofloxacin, Difloxacin, Enrofloxacin, Ibafloxacin, Marbofloxacin, Orbitfloxacin, Sarafloxacin
G-, modernately G+ (staph,strep,myco are resistant!) active against pseudomonas! (ciprofloxacin) , IC pathogens!

3rd gen (mainly hu):Balofloxacin, levofloxacin, sparfloxacin, temafloxacin : G+(+staph and strep). G- ,pseudomonas and IC pathogens

4th gen: (mainly hu): Pradofloxacin (used in vet) Gram+ve, Gram-ve, Pseudomonas, anaerobes, intracellular pathogens.
* effective against MRSA, streptococci, anaerobes( prevotella spp)
•

Question 3

Resistance

Answer 3

1. Chromosomal mutation
2. gyrase A gene mutation- 1st gene resistance
3. gytase A+B mutartion - full resistance
   * freq in zoonotic E.coli, salmonela and campy
   * membrane proteins
   * inc. bacterial efflux
   * Cross resistance is complete within the generations
   * Plasmid mediated resistance

Question 4

Pharmacokinetics

Answer 4

• except the 1st gen.
• absorption: excellent
• Distribution: Excellent, good good special barriers penetration (CSF, ocular)
• concentrated within phagocytic cells (reduction of survival of intracellular pathogens).

Question 5

Metabolism

Answer 5

except 1st gen

• Partially metabolized , based on CYP450A
• metabolites may be active (Enrofloxacin to ciprofloxacin)
• Eliminiation: Kidneys as an active drug (UTI) , bile, enetrohepatic recirculation can prolong its action.

Question 6

Indication

Answer 6

• used when thiere is no other antibiotic that can be used (to decrease ressistance)
• UTI, GI -best
• respiraroty,mycoplasmosis,soft tissue,pyoderma,osteomyelitis,prostitis,eye infection, gingivitis, meningitis

Question 7

Side Effects

Answer 7

• inhibition of load bearing cartilage development
• retinopathy (fe)- blindness
• CNS sign (epilepsy)
• Dysbacteriosis (NOT in eq) , vertigo, dizziness,headache
• GI: vomitting,diarrhoea , abdominal pain
• photosensitivity , pruritis
• cardiac toxicity, hepatotoxicity

Question 8

combination

Answer 8

• Synergic with: Betalactams, aminoglycosides, vancomycin
• staphiloccocus aureus: ciprofloxacin+azlocillin // levofloxacin + oxacillin
• pseudomonas aeruginosa (ciprofloxacin+imipenem/azlocillin/amikacin
• antagonistic interaction: chloramphenicol , rifampin