pharmacology 4 Flashcards
beta lactams antibiotics include
penicillin
cephalosporins
carbapenems
monobactams
ring structure
mechanism of action for beta lactams
penetrate the outer cell wall
bind to and inhibit penicillin binding protein (PBRs)-transpeptidase enzymes required for cross-linking of cell precursors
inhibition of cross linking-opens channels through the cell wall to create pores and allows fluid into the cell, causing cells swelling and death
general pharmacokinetic for beta lactams
low plasma protein binding-distribute well to the extracellular fluid in most tissues-exception cefovecin and ceftiofur
hydrophilic-minimal intracellular concentrations
do not distribute well to protected sites
metabolism-minimal, exception-ceftiofur
elimination-glomerular filtration and tubular secretion
very high concentration in urine
1000x higher than plasma
short half life and require frequent dosing
some PAE against gram + bacteria-penicillin and streptococci
pharmacodynamics
time-dependent
T>MIC 50% of the dosing interval
some say 80% for gm -
if immunosuppressed T>MIC 90-99%
constant rate infusion
penicillins
benzylpenicillin-penicillin G
first beta lactam
first penicillin
first antibiotic
benzylpenicillin
still effective against strep species
anaerobes
gm - bacterial are RESISTENT
inactivated by beta lactamases
spectrum
gm + streptococci anaerobes
penicillin g route of administration
oral absorption limited-degraded in gastric acid
IV formulation-potassium or sodium salt$$$
IM/SC formulation-complexed with procaine or benzathine
longer half life and can be dose less frequently
vet produces$
aminopenicillins
ampicillin and amoxicillin
good oral absorption in small animal-amoxicillin>ampicillin
limited to no oral absorption in large animals
increased spectrum against gm - bacteria
lower urinary tract
#1 drug in cats
#2 in dogs
cephalosporins-1st generation
active against gm + bacteria includes some beta-lactamase positive staphylococci
includes cefazolin, cefadroxil and cephalexin
cefazolin has the most activity against gm - bacteria
cephalexin-very commonly prescribed in dogs
cephalosporins-2nd generation
greater activity against gm - bacteria
activity against gm + bacteria is similar
rarely used in veterinary species
cephalosporins-3rd gen
have the most activity against gm - bacteria
still retain activity against gm + but lesser
not used clinically
ceftiofur, cefovecin and cefpodoxime proxetil
cephalosporins 4th generation
broad spectrum
EU and UK
approval for BRD denied by FDA
Cephalexin
oral use in dog and cat
FDA approved chewable tablet in dogs
dermatitis caused by non-methicillin/oxacillin resistant staphylococci
cefazolin
IV use in dogs and cats (sometimes horses)
extralabel use
surgical prophylaxis
administer within 60 minutes of incision
does ever 90-120 minutes until wound closure
cefpodoxime proxetil
labeled for use in dogs-skin and soft tissue infection
has been used safely in cats and foals
longer half life-once daily-better owner compliance
prodrug-ester improves oral absorption
cefovecin
FDA approved for the treatment of skin infection in dogs and cats (convenia)
single subcutaneous dose-half life due to high affinity protein binding
provides therapeutic concentration for up to 14 days
2nd antibacterial in cats
ceftiofur
FDA approved for use in (dogs), horses, chickens, turkeys, cattle, goats, sheep and swine
main cephalosporin used systemically in large animals-three formulations available
ceftiofur sodium (naxcel)
ceftiofur hydrochloride (excenel)
ceftiofur crystalline free acid (excede)-exceded MIC of bacteria for a long time
ceftiofur crystalline free acid (Excede)
long acting
single SC dose at the base of the ear in cattle
single IM dose in swine
IM dose in horses-repeated once in 4 days
injection site reactions are common
long half life due to extended release formulation
cephalosporin-extra label use in food animal
prohibited by FDA in major food producing species-cattle, swine, chicken and turkey
exception: cephapirin-intramammary, indications not on the label-all other label indications met (dose, route, duration of therapy)
no prohibition in minor food-producing species
ex. cattle label for naxcel says BRD and foot rote-can be used for metritis
beta lactams adverse effects
relatively rare-hypersensitivity reaction
cross-reactivity between penicillin and cephalosporins
at very high concentrations can inhibit GABA
cause CNS excitement and seizure
can occur with other beta-lactams
procaine reaction-do not give to a horse
gastrointestinal effects (dog and cats)
beta lactam drug interactions
aminoglycosides-combine in animal not in syringe
combine in syringe would cause inactivation-does not precipitate
beta lactam mechanism of resistance
methicillin resistance-mediated via the MecA gene-encodes for PBP2a
resistant to all beta lactams
reduced penetration of drug into bacteria-gm - capsule
altered or reduced number of porins-channels the antibiotics can use to cross cell membrane
#1 is enzyme mediated degradation-beta-lactamases, penicillinases, cephaloporinases, carbapenemases
beta lactamase inhibitors
includes clavulanic acid, sulbactam and tazobactam
mechanism of action-combine with beta-lactamase enzymes to form an inactive complex-gm -and gm +
co administered antibiotics is then able to exert its effect
also bind to different PBP-bactericidal effects
not sufficient to ever administer alone
