Pharm - Cell Wall Inhibitors Flashcards
What are the two types of B-lactam antibiotics?
Penicillins
Cephalosporins
Explain the mechanism of action for a B-lactam antibiotics
penetrate the outer cell wall and binds to and inhibits penicillin binding proteins (PBPs) which are transpeptidase enzymes required for cross-linking of cell wall precursors
ie by inhibiting PBPs, the abx interferes with the structure putting a hole in the cell wall allowing fluid in and eventually the rupturing and killing of the cell
Are B-lactam antibiotics considered bacteriocidal or bacteriostatic?
bacteriocidal
Explain the general principles of pharmokinetics associated with B-lactams
Are B-lactam antibiotics hydrophobic or hydrophilic? What does this mean?
Hydrophilic - water soluble
minimal intracellular concentrations
do NOT distribute well to protected sites
Do B-lactam antibiotics have a high or low plasma protein binding? Why is this significant?
Low
distribute well to the extracellular fluid in most tissues
Are B-lactam antibiotics metabolized?
minimally
How are B-lactam antibiotics eliminated?
glomerular filtration and tubular secretion
Why is the elimination of B-lactam antibiotics significant clinically?
very high conc. in urine so are very efficient at treating UTIs
What is the short life of B-lactams? How does this correlate with dosing?
short half life - frequent dosing
B-lactams are time dependent. If dosing for 12 hours, what will the time above MIC be?
6 hours
What bacteria are Benzylpenicillins effective against?
Streptococcus and anaerobes
What are penicillins inactivated by?
B-lactamases
Explain the varying routes of Penicillin G and which are the most effective
Oral - limited
IV - potassium or sodium - HUMAN PRODUCT SO EXPENSIVE
IM/SC - complexed with procaine or benzathine which have longer half lives and can be dosed less frequently
Why does Benzathine penicllin suck?
Sticks around for a long period of time but at subclinical concentrations
The old label on penicillin was 6600 IU/kg, what is it now and why?
22,000 IU/kg because it was used so frequently that now a higher dose is needed for it to be effective
What two drugs in the aminopeniciillin class are used very frequently in small animals
ampicillin
amoxicillin
Which aminopenicillin has a better oral absorption in small animals, although both have a considerably good absorption?
amoxicillin
Which drug is limited to NO ORAL ABSORPTION in large animals?
amimopenicillins
Aminopenicillin has an increased spectrum against gram _______ bacteria
negative
What two drugs are part of the anti-staphylococcal penicillins?
methicillin, oxacillin
What organisms do anti-staphylococcal penicillins have little activity against?
gram neg or anaerobes
Bacteria reported to be resistant to oxacillin should also be considered to be resistant against _____________
all other B-lactam antibiotics
What are the classifications of Cephalosporins?
1st
2nd
3rd
4th
Generations
What are 1st generation drugs active against?
gram-positive bacteria including some B-lactamase positive staphlococci
What generation are cefazolin, cefadroxil, and cephalexin considered to be under?
1st generation
Which of the 1st gen cephalosporin drugs have the most activity against gram-negative bacteria?
cefazolin
What 1st gen cephalosporin drug is commonly prescribed for dogs?
Cephalexin
What are 2nd generation drugs active against?
gram-negative bacteria
What generation are the drugs cefoxitin, cefotetan, and cefaclor under?
2nd generation
Which generation of Cephalosporins are often used before dental procedures as it has activity against anaerobes and dental disease?
2nd
What are 3rd generation drugs active against?
gram-negative
What generation is ceftiofur, cefovecin, cefpodoxime, and proxetil under?
3rd
What generation are cefepime and cefquinone under?
4th generation
As you go from 1st to 4th, which has more importance in human medicine? Which is more active against gram-negative while still retaining activity against gram positive
4th gen more important in human med
increasing activity against gram-neg from 1st to 4th
What species is Cephalexin approved in, whats the preferred route, and what is it used to treat?
oral use in dogs and cats for dermatitis caused by non-methicillin/oxacillin resistant staphylococci
What species is cefazolin approved in, whats the preferred route, and what is it used to treat?
IV use in dogs and cats (sometimes horses) for surgical prophylaxis
What species is Cefpodoxime approved in, whats the preferred route, and what is it used to treat?
oral use dogs for skin and soft tissue infectious
Besides dogs, which species has Cefpodoxime been safely used in?
cats and foals
What is the half life of Cefpoxoxime? How does this relate to dosing?
longer half-life leading to a once daily dose
What is Cefovecin and what species has it been approved for, what is the route of administration?
Convenia - SQ single dose approved for treatment of skin infections in dogs and cats providing therapeutic concentrations for up to 14 days
Why can long-acting antibiotics be dangerous?
effects persist longer
adverse effects last longer
not fact acting - not useful for an emergency
What is Ceftiofur, what species has it been approved for and what are the 3 formulations available?
Main Cephalosporin used systemically in LA but approved in dogs (mostly), horses, chickens, turkeys, cattle, goats, sheep, swine
three formulations
- ceftiofur sodium (Naxcel)
-ceftiofur hydrochloride (Excenel)
- ceftiofur crystalline free acid (Excede)
Where is ceftiofur crystalline free acid (Excede) administered, in what species, and how long does it last?
long lasting administered in the base of the ear in cattle
What are the species differences in the admin of ceftiofur crystalline free acid (Excede) in cattle, swine, and horses?
cattle - base of the ear
swine and horses- IM
While in cattle and swine Ceftiofur crystalline free acid (Excede) are given as a single dose, which species requires a second dose? What is the timing of this second dose?
horses - repeated once in 4 days
Extralabel use of cephalosporins is prohibited in ___________
major food producing species
While adverse reactions of B-lactam antibiotics are rare, what are 5 different ways in which an adverse reaction can occur?
Hypersensitivity reactions
high concentrations inhibiting GABA
Procaine reactions
GI effects
B-lactam antibiotics can rarely cause adverse effects such as GI effects which species is this prevalent to and what occurs?
dogs and cats - vomiting with high oral doses due to irritation of the gastric mucosa
horses and rabbits - high incidence of antibiotic associated colitis with oral admin
What drug reactions are associated with B-lactam antibiotics?
aminoglycosides
If having to give B-lactam antibiotics and aminoglycosides, should they be mixed in the same syringe or should the animal be given two injections, one with the B-lactam and the aminoglycoside in another?
separately
What are the 3 mechanisms of resistance pertaining to B-lactam antibiotics?
methicillin resistance mediated by MecA gene which encodes for penicillin binding protein
reduced penetration of drug into bacteria due to gram-neg capsule or altered/reduced number of porins
enzyme mediated degradation by beta-lactamases, penicillinases, cephalosporinases, etc
What are 3 B-lactamase inhibitors?
claculanic acid, sulbactam, and tazobactam
What is the mechanism of action for b-lactamase inhibitors
combine w/ b-lactamase enzymes to form an inactive complex allowing for co-administered abx to exert its effect
can also bind to different PBPs to have bacteriocidal effects
Amoxicillin + clavulanic acid –>
clavamox
Ampicillin + sulbactam –>
Unasyn
