Antibiotic therapy Flashcards
fluoroquinolones
Which is the parent compound of the quinolone group
Nalidixic acid
What is the mechanism of action of fluoroquinolones
They inhibit the topo-isomerase II (also known as DNA gyrase) in gram-negative bacteria or the topo-isomerase IV in some gram-positive bacteria
- This results in inhibition of DNA replication and transcription
Topo-isomerases are enzymes that twist or untwist bacterial DNA into “supercoils”
- If the supercoils cannot relax, then replication enzymes such as DNA polymerase cannot move along the strand
Quinolones are highly effective in blocking TP-II, but TP-IV is less susceptible, which partially explains why these drugs are less effective against gram-positive bacteria
Mammalian TPs are much less susceptible to the effects of these drugs
What is nthe spectrum of action of fluoroquinolones
They are mainly effective against gram-negative organisms (especially enteric organisms)
- they may have activity against some gram-positive and facultative anaerobic bacteria
They have poor activity against obligaate anaerobes and Streptococcus
Fluoroquinolones are bactericidal, concentration-dependent drugs
How is resistance to fluoroquinolones acquired
Resistance is primarily chromosomal rateher than plasmid mediated
It comes when structural changes to DNA gyrase cause a sunstantial decrease in the binding affinity to fluoroquinolones
Unfortunatelyy, resistance to some of these drugs is now relatively common
Which generation of fluoroquinolones is common usage in veterinary medicine
Third-generation compounds with improved pharmacokinetics, increased bioavailability, less toxicity and broader antibacterial spectrum
What can influence the bioavailability of fluoroquinolones
Food, antacids, sucralfate
Their administration should be separated from the fluoroquinolones by approximately 2 hours
Explain why fluoroquinolones can be used for UTI
Approximately 50% of the absorbed drug are excreted unchanged in the urine
- the remainder of the dose is excreted unchanged in the bile
This makes them useful for urinary and GI tract infections
What is the spectrum of action of fluoroquinolones
They are minimally protein-bound and are lipophilic which means they penetrate well into tissues of the body
They accumulate in phagocytes, making them useful for some intracellular pathogens such as rapidly growing mycobacteria
The fourth generation (eg moxifloxacin), despite their price, may be useful for lepromatous and slowly growing mycobacteria
What are the possible side effects of fluoroquinolone
Overdosage may cause:
- GI (vomiting/diarrhoea)
- Cardiovascular (hypotension, tachycardia and other arrhythmias)
- Central nervous system (seizures)
- Ocular toxicity
The most characterized toxic effect of the quinolones in cats is the propensity to cause retinotoxicity (mostly observed with dses of enrofloxacin about 5 mg/kg, PO, q24h)
The inhibition of proteoglycan synthesis and subsequent cartilage degeneration is not as significant in cats as it is in dogs
What are the characteristics of pradofloxacin
Pradofloxacin is a broad spectrum third-generation fluoroquinolone bactericidal antibiotic, with gram-negative activity similar to other fluoroquinolones, but it has enhanced aerobic gram-positive activity and activity against anaerobes
It is the only antibiotic shown to date that can eliminate Mycoplasma haemofelis from the blood of experimentally inoculated cats
What is the dosage for pradofloxacin
Oral suspension: 5-7.5 mg/kg, PO, q24h
Oral tablets: 3-4.5 mg/kg, PO, q24h
What are the side effects of pradofloxacin
Pradofloxacin at recommended dosages appears to be well toleraated with diarrhea/losse stools occasionally reported
If using at higher than labeled dosages, or past 7 days, it is recommended to check the white blood cell count periodically
Does pradofloxacin have a retinal toxicity in cats such as enrofloxacin
No
