Macrolides and Fluoroquinolones Flashcards
Are macrolides knows to be safe?
Yes! One of the safest classes of antibacterial drugs
What are the key pharmokinetic points about macrolides?
- penetrate cells better than most classes
- concentrate in the lungs
- Newer macrolides have longer half lives
What is the mechanism of action of a macrolide?
Inhibit protein synthesis
What is the spectrum of activity of macrolides?
- relatively broad
- mostly GP ae. and anaerobes but also can be effective against GN ae. and atypical bacteria
What are some important uses of macrolides?
- intracellular pathogens
- respiratory infections
- erythromycin inhibits P450 enzymes (recall P450 is an enzyme that metabolizes drugs = long half life)
What is the spectrum of activity of newer macrolides?
- gram negative aerobes
- several injectable drugs for livestock
- long half lives
- human labelled drugs sometimes used for bacterial pneumonia in non-food producing animals
What do we mainly use newer macrolides for in kivestock?
Respiratory disease
What do we use Tilmicosin for?
- bacterial pneumonia
- effective against GN ae.
- IV injection is fatal
- drug is fatal to swine
What do we use Tulathromycin for?
- bacterial pneumonia (cattle and swine)
- effective against GN ae.
- half life is approximately 90 hours, lung elimination half life is about 1 week = single does therapy
What do we use Gamithromycin for?
- Bovine respiratory disease
How do we commonly see resistance present in macrolides?
- acquisition of a plasmid-encoded efflux pump
- a resistant cell shares with a sensitive cell
What are the main adverse effects of macrolides?
- Tissue irritation: IM injection = pain, PO = vomiting (erythromycin)
- Oral toxicity in herbivores
- Tilmicosin can cause rapid cardiac fatalities
How would we typically use a fluoroquinolone?
As a second-line drug for infections resistant to the first-line drugs.
What is the mechanism of action of a fluoroquinolone?
- Damage DNA (inhibit bacterial DNA gyrase and topoisomerases)
- bactericidal effect
What is the spectrum of activity with a fluoroquinolone?
- many GN ae.
- staph (GP ae.)
- many atypical bacteria
- completely ineffective against anaerobes
- recall this is similar to gentamicin
Are fluoroquinolones absorbed well orally?
Yes
Where do fluoroquinolones distribute to in the body?
- most tissues including prostate and especially the lungs
- not well in CNS and skin
How are fluoroquinolones eliminated?
- mostly unchanged in the urine
- long half-lives
What are the main adverse effects of fluoroquinolones?
- Cartilage damage in juvenile patients (many veterinary species are highly sensitive)
- retinal degeneration in cats
- can trigger seizures in epileptics
What is resistance like in fluoroquinolones?
- often sudden due to mutations in bacterial DNA/gyrase topoisomerase genes
- some mutations have resistance to one drug and some to all FQs
- there are also plasmid-borne resistance mechanisms
What is the main issue with chloramphenicol?
- it is very potent to handle and it can cause fatal idiosyncratic aplastic anemia in humans
- this is very rare and not does related
Do we use chloramphenicol?
- starting to become more popular due to rising MRS and MRSP resistance to other drug classes
- banned in food producing animals
What type of AMD does CVMA suggest we try to use as veterinarians?
“drugs of lesser importance in human medicine in preference to newer generation drugs”
What drug classes should we avoid as veterinarians for the sake of resistance?
- Fluoroquinolones
- potentiated penicillins
- 3rd generation cephalosporins
