Fluoroquinolones

Question 1

What is the MOA of fluoroquinolones?

Answer 1

Only Class Inhibiting. DNA Synthesis. Rapidly Bactericidal. Concentration-dependent killing
Inhibits 2 Bacterial Enzymes.

Inhibits topoisomerase II (DNA gyrase)
Inhibits transcription and replication Gram -
Inhibits topoisomerase IV
Inhibits separation of replicated chromosomal DNA Gram +

Question 2

What are the mechanisms of resistance?

Answer 2

Efflux Pumps
Changes in Porin Structures
Mutations in chromosomal genes

Question 3

What is the spectrum of activity?

Answer 3

Enterobacter
E coli
H influenzae
M cattarhalis
Salmonella
Shigella
Campylobacter
Legionella

Poor activity against Anaerobes

Question 4

What is the classification of fluoroquinolones?

Answer 4

First Generation (Norfloxacin) - least active
Second Generation (Ciprofloxacin, Ofloxacin) - gram -
Third Generation (Levofloxacin)
Fourth Generation (Moxifloxacin, Gemifloxacin) - gram +

Question 5

What are the general pharmacokinetics?

Answer 5

A - Good oral bioavailability. However, absorption reduced by chelation
D - Wide tissue distribution (X norfloxacin). Kidneys, lungs, bone, stool, WBCs.
M- Majority hepatically metabolized. Variability in half lives (3 – 10hrs).
Some long enough to allow once daily dosing
Elimination.
Renal elimination (tubular secretion)
Dosage reduction necessary if CrCl < 50ml/min
(X: moxifloxacin)

Question 6

What are the adverse effects?

Answer 6

GIT Effects,Nervous System Effects, Hypersensitivity Reactions, Arthropathy, QT Prolongation, Tendinitis and Tendon Rupture

Question 7

What are some clinical uses?

Answer 7

UTIs and Prostatitis (Second generation agents)
STDs (Second generation agents)
GIT infections (Traveller’s diarrhoea, Second generation agents)
Bone, joint and soft tissue infections (Osteomyelitis: S aureus + gram-ve rods) Respiratory tract infections (RTIs) (Moxifloxacin, Levofloxacin or gemifloxacin)
Pseudomonal and pneumococcal infections (in cystic fibrosis patients) (Ciprofloxacin)

Question 8

What are some drug interactions?

Answer 8

Multivalent cations, Sucralfate, Theophylline and caffeine, Warfarin, Erythromycin, Drugs causing hypokalaemia
Class IA or III antiarrhythmics, TCADs
Glibenclamide, Probenecid

Question 9

What are some counselling tips you can give to the patient?

Answer 9

Take on empty stomach
Do not administer antacids/dairy products and other multivalent cations within 2 hours of taking the dose
Stop treatment if tendonitis symptoms start
Maintain adequate fluid intake