Antimicrobial use in Lung Infection 2 Flashcards
what are examples of aminoglycosides
streptomycin
neomycin
kanamycin
gentamicin
tobramycon
amikacin
netilmicin
what is the shape of aminoglycosides
highly cationic polar molecule
highly ionized at physiological pH –> doesn’t distribute very well
how do streptomycin enter bacteria
oxygen dependent polyamine carrier to enter –> more efficient with B-lactams (like getimicin, work together –> B-lactams interfere with cell wall so aminoglycosides can get into the cell)
what is the mechanism of action of aminoglycosides
- bind to 30S subunit of bacterial ribosome
- use anticodones and codones that mismatch and cause them to bind in incorrect place
- protein will be truncated and non-functional
- cell won’t work
- destroys itself
list 6 pharmacokinetic features of aminoglycosides
- highly polar with low lipid solubility
- very poor absorption from GI tract –> give another route IM, SC
- therapeutic concentrations in joints and pleural and pericardial fluids
- don’t cross BBB or penetrate vitreous humour of eye or prostate
- not metabolized, excreted unchanged by kidney (glomerular filtration) (high accumulation in kidney cortex and can cause damage)
- selective binding to certain tissues esp kidney cortex (not used in patients with renal impairement)
what is ototoxicity of aminoglycosides
damage to vestibular apparatus cells –> disturbed balance, ataxia, vertigo, nysatgmus
cochlear: damages sensory cells of cochlea, causing deafness
what is the neprotoxicity of aminoglycosides
usually following prolonged therapy or persistent high plasma through concentrations
urine contains protein and tubular cast
what are examples of fluoroquinolones (6)
norfloxaxin
enrofloxacin (batril)
danofloxacin (advocin)
marbofloxacin (marbocyl, aurizon0
orbifoxacin (prosatex ear drops)
pradofloxacin (veraflox)
what are fluoroquinolones
fluorinated quinolones with mostly broad spectrum of activity
bactericidal
what is the mechanism of action of fluoroquinolones
rapid concentration-dependant killing (bactericidal)
enter bacteria through porins –> reduction in permeability of porins to quinolones may confer resistance
what is the spectrum of activity of fluoroquinolones
broad
highly active against gram - (aerobes)
gram positive (aerobes)
intracellular bacteria (chlamydia, legionella, brucella spp)
mycoplasma
relatively ineffective against obligate anaerobes
bactericidal
what is the metabolism of fluoroquinolones
some unchanged (ofloxacin)
some metabolized in liver (cipro-, enrofloxacin)
what is the excretion of fluoroquinolones
parent drug and metabolies excreted in urine, bile
renal excretion: glomerular filtration & tubular secretion –> high urinary conc of parent drug
in milk
enterohepatic recycling may occur
what is the half life of fluoroquinolines
half life varries with species and drug variations (3-14 h)
what is the clinical use of fluoroquinolines
what is the absorption and bioavailability of fluoroquinolones
highly orally bioavailable
rapid absorption (80-90%)
what is the IM and SC absorption of fluoroquinolones
100%
what is the distribution of fluroquinolones
low protein binding and extensive distribution
enters phagocytes
what are the fluoroqiunolone concentrations in tissues
liver, kidney, urinary tract, lung, prostate, bone, skin
in fluids, interstitial, bronchial secretions, bile
most do not cross BBB
what interferes with fluoroquinolone absorption
aluminium and magnesium antacids
what indications would fluoroquinolones be the drug of first choice in dogs and cats (6)
- UTI with pseudomonas aeruginosa
- prostate infection in dogs
- skin, soft tissue and wound infection
- serious G-negative systemic infection
- serious resp infections
- osteomyelitis caused by G-negative aerobes
what are the indications of fluoroquinolones in small mammals
rabbits, mice, rats and exocits for skin and visceral infection
do not cause GI disturbance as with beta-lactams or macrolides
what are the indications of fluoroquinolones in birds
drinking water or injection
dose is higher than in mammals because of faster clearance rates
what are the indications of fluoroquinolones in large mammals
good safety profile in adult horse but none currently licenced
cattle and sheep (marbofloxacin, enrofloxacin, danofloxacin) for BRD (excreted in milk)
pigs: marbofloxacin, enrofloxacin, danofloxacin
what is the toxicity of fluoroquinolones
considered relatively safe
erosion of weight bearing cartilage –> dogs most susceptible, contraindicated in young growing cats and dogs
some CNS problems may occur and associated with CNS pathology (GABA)
ocular problems in cats (enrofloxacin)
what is the spectrum of enrofloxacin
broad spectrum
wide variety of species including birds and reptiles
what is the mechanism of enrofloxacin
rapid killing of bacteria
what is the absorption and bioavailability
highly bioavailable
rapid absorption
what are the tissue concentrations of enrofloxacin
tissue concentrations frequently exceed plasma concentrations
crosses placenta into aqueous humour and CSF
low plasma protein binding
how is enrofloxacin excreted
renal
what are the trade names of enrofloxacin
baytril
bayer
xeden
alstoe
what is the activity of marbofloxacin
enterobacteriaciae, pasteurella
what is the absorption of marbofloxacin and excretion
adequate plasma levels maintained for 24 hours after SC injection (40%) parent drug excreted (67% uring, feces 33%)
what are the trade names of marbofloxacin
marbocyl, aurizon, vetoquinol
what is marbofloxacin used for
resp infection in cattle and pig
