Derm Antibiotics Flashcards
percutaneous administration
application of the drug to the skin
topical or transdermal
topical administration
achieves local concentrations
transdermal administration
achieves systemic concentrations
what is the major barrier to drug administration on the skin
stratum corneum
how do drugs move through the epidermis
passive diffusion either intracellular or intercellularly
what drug factors affect drug movement through the skin
solubility, concentration, molecular weight, vehicle
- must be able to partition out of vehicle
- must be able to diffuse through stratum corneum/epidermis
once it reaches dermis –> absorbed into circulation
what cutaneous factors affect drug movement through the skin
hydration, thickness, integrity of stratum corneum, blood flow
- skin is POORLY perfused; systemically administered drugs take longer to reach the skin and are in lower concentrations
broad spectrum antibiotics
effective against a wide range of microorganisms
narrow spectrum antibiotics
effects against a limited range of microorganisms
bacteriostatic
ability to inhibit growth of an organism; relies on animals own immune system to kill the organism
- tetracyclines, lincosamides, sulfonamides, trimethoprim
bactericidal
ability to kill an organism
- beta-lactams, Fluoroquinolones, aminoglycosides, lincosamides
MIC
minimum inhibitory concentration
the target concentration to achieve therapeutic effect
PAE
post-antibiotic effect
the period of suppression of bacterial growth after a short exposure of the organism to the drug
drug will still have effect after concentration falls below the MIC; allows for longer time between doses
time-dependent PK:PD
efficacy of the drug depends on the amount of time spent above the MIC
PDC > MIC for majority of dosing interval
concentration dependent PK:PD
efficacy of the drug depends on reaching a certain concentration
Cmax / MIC = 10-12
mechanisms of antibiotic resistance
- inactivating enzymes
- decreased drug accumulation
- altering binding sites
- development of alternative metabolic pathways
first tier antimicrobials
“go-to” drugs that are effective for most infections without requiring susceptibility testing
- clavamox
- 1st and 3rd generation cephalosporins
- clindamycin
- lincomycin
- potentiated sulfonamides
second tier antimicrobials
used when 1st tier antimicrobials are ineffective and when indicated by susceptibility testing
- doxycycline
- minocycline
- chloramphenicol
- fluoroquinolones
- aminoglycosides
examples: B-lactams
penicillins:
- clavamox
cephalosporins:
- cephalexin, cefadroxil
- cefovecin (Convenia), cefpodoxime
B-lactams: PK/PD and MOA
time dependent
bactericidal - disrupts proteoglycans in cell wall
B-lactam resistance
- dec. penetration through cell wall
- efflux through pumps
- altered penicillin binding proteins
- B-lactamases
B-lactamases
enzymes that inactivate B-lactam antibiotics
B-lactamase inhibitors
bind to B-lactamase enzymes to inhibit activity
do NOT have antibacterial activity
ex. clavulanic acid
B-lactam side effects
safe
- gi upset
- CNS reactions
- hypersensitivity
lincosamide examples
clindamycin, lincomycin
lincosamide PK/PD and MOA
time-dependent
bacteriostatic at low dose
bactericidal at high dose
inhibits protein synthesis
lincosamide resistance
altered drug binding by bacterial ribosomes
lincosamide adverse effects
rare in small animals
contraindicated in horses due to enteritis/colitis
potentiated sulfonamide examples
ormetoprim-sulfadimethoxine
trimethoprim-sulfadiazine (TMS)
pot. sulfonamide PK/PD and MOA
bactericidal
- each component is bacteriostatic on their own, bactericidal when combined
inhibits folic acid synthesis
potentiated sulfonamide resistance
- increased PABA production
- decreased sulfonamide binding
potentiated sulfonamide side effects
- crystalluria
- dry eye
- hypersensitivity
- anemia
- thrombocytopenia
tetracycline examples
doxycycline
minocycline
tetracycline PK/PD and MOA
time-dependent
bacteriostatic
- inhibits protein synthesis
tetracycline resistance
- decreased drug uptake
- active transport out of cell
- altered target
tetracycline adverse effects
- GI upset
- esophageal strictures
- binding to bone and teeth
chloramphenicol PK/PD and MOA
time dependent
bacteriostatic & broad spectrum
- inhibits protein synthesis
chloramphenicol resistance
- production of metabolic enzymes
chloramphenicol side effects
- anemia
- GI upset
fluoroquinolones examples
enrofloxacin (Baytril)
ciprofloxacin
fluoroquinolones PK/PD and MOA
concentration dependent
bactericidal
- inhibits DNA replication
fluoroquinolones resistance
mutation in gene coding binding site
fluoroquinolones adverse effects
- retinal degeneration in cats
- GI upset
- developmental arthropathy
aminoglycoside examples
amikacin
gentamicin
aminoglycoside PK/PD and MOA
concentration dependent
bactericidal
- inhibits protein synthesis
aminoglycoside administration
injectable only
aminoglycoside side effects
- ototoxicity
- nephrotoxicity
what is the goal of an antibiotic dosage regimen
maximize drug concentrations at the site of infection
what causes therapeutic failure
- poor drug penetration to target
- drug resistance
- inadequate dose
- inadequate duration of administration
