fINAL: aNTIMICROBIAL dRUGS Flashcards
How are antimicrobial drugs classified?
four characteristics
They can be bacteristatic, bactericidal, and are classified by microorganism and antibacterial spectrum.
What is the difference between concentration and time dependent activities of antimicrobials? What are the dosing startegies to optimize each?
concentration verse time, one is more important than the other.
For concentration, a higher dose is more important so hugher dose less frequently. For time the frequency is more important so lower dose more frequently.
What is MBC and MIC and how are they determined experimentally?
MBC is minimum bactericidal concentration and is determined by the min concentration that kills 99.9% bacteria used in MIC testing.
MIC is minimum inhibtory concentration and is the lowest concetration of a drug required to inhibit visible growth of bacteria in a test tube.
What is the relationship between MIC and breakpoints? How do you select an agent for use based on these values?
If the MIC is above the breakpoint value, it will not be an effective dose. MIC is species specific and the breakpoint can depend on the sensitivity of the bacterium and the achievable drug concentraition.
What is PK, PD, AUC, Cmax, T>MIC, and PAE? When are they important?
PK is dose and exposure
PD is exposure and response
AUC is area under the curve, high doses less frequently or low doses more frequently is equivalent in this regard. patient compliance is important here.
Cmax is to know how high you can get, not how long. Important for toxicity risks. is cmax is important, you want higher doses less frequently.
time above MIC is how long the drug stays above target. This is important in extended release drugs.
PAE is the persistant inhibition of bacterial growth even when the drug goes below MIC.
When do you want to give drugs in combination and what effects can they have?
They can have additive, synergistic and antagonistic effects.
You want to do combinations when you need to hit something hard, to avoid toxicity and if you have a polymicrobial infection.
Quinolones and Fluroquinolones
What is the MOA?
Inhibition of bacterial DNA gyrase and/or topoisomerase IV, which leads to the inhibitoion of DNA supercoiling and replication. They enter cells via porins and replicate quickly. (This is bacteria specific and they do not do this in mammalian cells)
Quinolones and Fluroquinolones
What is their effect, PK, and activity?
Concentration dependent
PAE in enrofloxacin and orbifloxacin
Has good oral absorption (divalent/trivalent cations can decrease this this nursing young or antacids)
volume of distribution (can reach CNS and eye in concentrations for for gram neg organisms, accumulated and macrophages and neutrohils so higher concentration in unhelathy tissues)
extended half-life, and good intracellular drug penetration.
best for gram neg aerobe, some gram positive aerobe. no anaerobes.
Quinolones and Fluroquinolones
What are any contraindications?
Retinal degeneration in cats with enrofloxacin at doses higher than 5mg/kg/day.
arthroppathies and cartilage regeneration in some species of immature animals. avoid use during rapid growth.
neurotoxic effects, GABA receptor inhibition.
occasional enterocolitis in horses as with many antimicrobials.
Quinolones and Fluroquinolones
What are the mechanisms of resistance?
Target modification: mutation in DNA gyase and topoisomerase IV
Decreased permeability: altered outer membrane porins
Efflux: induced efflux
Target protection: quinolone resistance gene qnr, protects DNA gryase.
banned in use in poultry products
Beta-Lactams
What is the MOA?
prevention of cell wall formation, bactericidal.
inhibition of peptidoglycan synthesis with penecillin binding proteins, PBPs
time dependent
beta-lactams
What are the mechanisms of resistance?
4 classes of beta-lactam enzymes produced by the bacteria, break the beta lactam ring and destroy the pharmacore. Now have beta-lactamase inhibitory drugs. cephalosporins more inherentyl resistant to these.
also has PBP modifications and reduced permeability and efflux.
beta-lactams
What is their effect, PK, and activity?
many poor oral absorption, short half lives, rapid elimination, mostly through kidneys (high urine concentration), small volume of distribution.
gram pos some gram neg
time dependent
beta-lactams
what are any contraindications?
not to be used in exotic species.
cephalosporins and carbapenems not first line use of drug, easy to cause sistance.
protein synthesis inhibitors
What are their MOA? activity? PK? effect? resistance?
tetracyclines
shared for all, bind to ribosomal subunits (ususally 30S and 50S) which inhibit formation of polpeptide chains and blocks protein synthesis.
tetracyclines: bind to 30S ribosomal subunit, inhibit tRNAS from binding
first true broad spectrum. first line of drugs in food animal, aquaculture species, exotics, and honeybees.
bacteristatic and time dependent
formulated as salts to give orally or parenterally.
energy dependent (H for Mg) efflux and removal of tetracycline from binding site.
osteotropic, poor oral bioavailability, primarily glomerular filtration, some biliary, enterohepatic circulation.
