Antimicrobials 4 Flashcards
what other beneficial effects do macrolides have other than antibacterial?
One of the safest classes of antibacterial drugs
Also have anti-inflammatory effects
pharmacokinetics of macrolides
- Penetrate cells better than most drug
classes - Concentrate in lung & lung macrophages
- Erythromycin, the first to be discovered, has a short half-life; newer macrolides have long half-lives
- Weak bases
mechanism of action for macrolides
Inhibit protein synthesis
Bacteriostatic effect
spectrum of activity for erythromycin (a macrolide)
Relatively broad
-Gram positive aerobes
-Anaerobes
-Some Gram negative aerobes (but not enterobacteriaceae)
-Some atypical bacteria
important uses for erythromycin
- Intracellular pathogens
- Respiratory infections
- In place of penicillin in animal with allergy
Erythromycin inhibits P450 enzymes,
(unlike most newer macrolides)
Increases T1/2 of other drugs that are metabolized by same enzymes (e.g., omeprazole, theophylline)
spectrum of activity for newer macrolides
- Most effective against Gram-negative aerobes (usually more effective than erythromycin)
>some efficacy against all other bacterial types
newer macrolides in veterinary medicine are generally used for what species?
livestock
* Several injectable drugs approved for livestock
Human-labelled drugs sometimes used for bacterial pneumonia in non-food- producing animals (horses, small animals)
how does the half life of newer macrolides compare with that of erythromycin
Longer half-lives: once-a-day admin
Newer macrolides approved for livestock are used mainly for the treatment of
respiratory disease
what is tilmicosin? what is it used for? what bacteria is it effective against? administration consideration?
Tilmicosin - macrolide
* For bacterial pneumonia
* Effective mainly against Gram-negative aerobic lung pathogens
* IV injection fatal; fatal to swine and various other non-approved species
what is tulathromycin? used in what species and for what diseases? effective against what kind of bacteria? half life?
Tulathromycin - macrolide
-used in cattle and swine for bacterial pneumonia
-Effective mainly against Gram-negative aerobic lung pathogens of cattle & swine
T1⁄2 = ~90 h; lung elimination T1⁄2 = ~1 week
>single dose therapy
what is gamithromycin and what is it used for?
Another similar new macrolide
* Single SC therapy for bovine resp. disease
macrolides resistance profile and mechanism
- May develop during therapy, due to mutation of ribosomal gene encoding efflux pump
- Acquisition of plasmid-encoded efflux pump
macrolides main adverse effects
1) Tissue irritation
* IM injection: severe pain from chemical irritation
* PO: vomiting – erythromycin stimulates motilin receptors (much more than newer macrolides)
> prokinetic GI effects > nausea +/- diarrhea; effect is highly variable from animal to animal
2) Oral toxicity in herbivores: potentially fatal rumen stasis, risk of serious colitis in hindgut fermenters (horses, rabbits) even by other routes
3) Tilmicosin can cause rapid cardiac fatalities in several species other than cattle (humans, swine, goats, horses) when administered parenterally
macrolides flash card: mechanism of action
Inhibition of protein synthesis (bacteriostatic effect)
macrolides flash card: main adverse effects
- Tissue irritation: pain on injection (all macrolides); nausea & vomiting (oral erythromycin)
- Potentially fatal colitis in hindgut fermenters (most likely with oral admin.)
macrolides flash card: general spectrum
- Erythromycin: Relatively broad
- Newer macrolides: a mix, but esp. Gram-neg aerobes
Macrolides Flash Card: health canada prudent use stats
Erythromycin: first-line
Newer macrolides: second-line
macrolides flash card: PK features
Concentrate in lung
Enter cells
Most newer macrolides have long half-lives
Erythromycin: inhibits P450 enzymes & stimulates motilin receptors
what is the most recent class of antimicrobial drugs (1989)?
Fluoroquinolones
Fluoroquinolones mainly used for what?
- Used mainly in small animals & exotics; some approved uses in horses & food animals
Fluoroquinolones are best thought of as second-line drugs to be used for infections resistant to first-line drugs (based on C&S)
Examples of veterinary fluoroquinolones
Generic names end in “-floxacin”
- Enrofloxacin (Baytril®)
- Orbifloxacin (Orbax®)
- Marbofloxacin (Zeniquin®)
- Difloxacin (Dicural®)
- Danofloxacin (A180®)
Fluoroquinolones Mechanism of Action
Damage DNA
* Inhibit bacterial DNA gyrases & topoisomerases
Bacteria must cleave their chromosome in order for supercoiling and reading of genes to occur
DNA gyrases & topoisomerases then re-attach the cleaved ends
Fluoroquinolones inhibit re-attachment > chromosome becomes fragmented
> bactericidal effect
Fluoroquinolones spectrum of activity
Similar to gentamicin
* Many Gram-neg. aerobes
* Staph but few other Gram-pos aerobes
* Several atypical bacteria
- All veterinary-licensed FQs are ineffective against obligate anaerobes
Fluoroquinolones phamacokinetics: absorption
- Generally very well absorbed orally by monogastric animals
(oral bioavailability close to 100%)
Fluoroquinolones phamacokinetics: distribution
- Most tissues including prostate, and esp. lung (as for macrolides, lung concentrations can be dozens of times higher than in other tissues)
- Poor: CNS, skin
Fluoroquinolones phamacokinetics: elimination
- Depends on drug but most are excreted primarily unchanged in the urine
- Long half-lives
Fluoroquinolones adverse effects
1) Cartilage damage
Rapid onset of cartilage lesions at moderate doses in immature animals > many veterinary species highly sensitive (e.g., puppies, foals)
2) Retinal degeneration in cats
Cats on high dosages of enrofloxacin
3) Can trigger seizures in epileptics (FQs inhibit inhibitory NT GABA)
Fluoroquinolones resistance mechanism and profile
Resistance often sudden & stable, due to mutations in bacterial DNA gyrase/topoisomerase genes
Some mutations confer resistance to one drug, some confer resistance to all FQs
Resistance may be minimized by using the highest safe dose
Plasmid-borne mechanisms have also been identified
Fluoroquinolones Flash Card: mechanism of action
Damage DNA (Inhibition of DNA gyrases & topoisomerases)
Fluoroquinolones Flash Card: main adverse effects
- Cartilage damage (immature animals)
- Retinal damage (enrofloxacin in cats)
- Reduction of seizure threshold
Fluoroquinolones Flash Card: general spectrum
Similar to gentamicin (but effective against more atypical bacteria)
Fluoroquinolones Flash Card: health canada prudent use stTS
Second-line (Ongoing prudent use problems)
FLUOROQUINOLONES FLASH CARD: PK FEATURES
Most have long half-lives (except enrofloxacin)
Oral absorption ~100%
Concentrate in lung
use of chloramphenicol in food animals?
banned in food producing animals
