Penicillins & Cephalosporins Flashcards
beta lactams target ______ by interfering with ______
cell wall synthesis, transpeptidase
bacterial cell wall is a cross-linked polymer called _______ which allows a bacteria to maintain its shape despite the internal pressure caused by ______
peptidoglycan, osmotic pressure differences
if the peptidoglycan fails to _____, the cell wall will lose its strength which results in cell lysis
crosslink
the cross linking reaction is catalyzed by a class of transpeptidases known as ________
penicillin binding proteins (PBPs)
a critical part of the cross linking process is the recognition of the ________ sequence of the NAMA peptide side chain by the PBP
D-Ala-D-Ala
beta lactams mimic the structure of the _______ link and bind to the active site of _____, disrupting the cross-linking process
D-Ala-D-Ala, PBPs
the ____ of the beta lactam ring is unusually reactive due to ring strain
amide
beta lactams acylate the _____ group on the serine residue of PBP active site in an irreversible manner
hydroxyl
what is the “secondary” mechanism of beta lactams that cannot occur without the primary mechanism
the bacteria detect a “defect” in its cell wall so it produces more peptidoglycan. in doing so, it produces autolysin, which is an enzyme produced by the bacteria to remove damaged cell wall for repair (slices off its own cell wall)
what are 3 mechanisms of bacterial resistance
efflux pumps, beta lactamases, mutation at genes that control PBP production
how do beta lactamases render beta lactams useless
they hydrolyze the amide bond of the beta lactam ring
beta lactams can easily penetrate _____ bacteria
gram positive
the outer membrane of ____ bacteria makes diffusion of beta lactams to the site of activity challenging
gram negative
any bacteria which lack ____ will not be affected by beta lactams
peptidoglycan
why are beta lactams relatively non toxic
they target PBPs exclusively, human cell membranes don’t have PBPs
penicillin __ is not orally active due to gut acidity
G
penicillin __ is orally viable and acid stable because of an added oxygen
VK
caution with high potassium/ESRD for which natural penicillin
VK
what was oral penicillin historically used for
dental prophylaxis in patients w/ prosthetic heart valves
when is oral penicillin actually used now
dental infections (soft tissue impacted molar), IM for syphilis, IV for susceptible severe streptococcal infections
______ are enzymes that hydrolyze the beta lactam ring, deactivating the drug
beta lactamases
beta lactamases can be present in both gram positive and negative bacteria, but they are a significant focal point in _____
gram negative, particularly those causing nosocomial infections
________ penicillins have a notable large R group which can block the beta-lactamases which hydrolyze the beta lactam ring
anti-staphylococcal
what are the oral anti-staphylococcal penicillins
cloxacillin, dicloxacillin
what are the IV anti-staphylococcal penicillins
oxacillin, nafcillin
what is the downside to anti-staphylococcal penicillins
due to the bulky side group, they have difficulty penetrating the cell membrane and are less effective against gram negative bacteria (no clinically relevant activity)
staphylococcus produces _____
penicillinase (beta lactamase)
Pen VK/G activity against staphylococci
extremely limited
Pen VK/G activity against streptococci
good activity against some: pyogenes is always susceptible, pneumoniae is mostly susceptible
anti-staphylococcal penicillin activity against staphylococcus
excellent activity against MSSA, no activity against MRSA
anti-staphylococcal penicillin activity against streptococci
little to no activity
_________ have more hydrophilic groups, allowing the drug to penetrate into gram negative bacteria via the outer membrane porins
aminopenicillins
downside to aminopenicillins
without the bulky R group of the anti-staphylococcal PCNs, they are once again susceptible to attack by beta lactamases
the hydrophilic groups of aminopenicillins also allow for greater absorption in the ____
GI tract
aminopenicillins are the drugs of choice for _____
enterococcus and listeria
acronym for aminopenicillin activity
HELPS: hemophilus, enterococcus, listeria, proteus, salmonella/shigella
PO frequency of administration for ampicillin
4x/day
PO frequency of administration for amoxicillin
3x/day
which aminopenicillin is more bioavailable
amoxicillin, less frequency of diarrhea too
ampicillin with regards to food?
should be administered PO on an empty stomach, food decreases absorption and peak plasma concentration
amoxicillin with regards to food?
may be taken without regards to meal
what are the IV beta lactamase inhibitors
sulbactam, tazobactam
what is the PO beta lactamase inhibitor
clavulanic acid
what are the first generation cephalosporins
cefazolin, cephalothin, cephalexin, cefadroxil
which first generation cephalosporins are PO
cephalexin, cefadroxil
what is the spectrum of activity for first generation cephalosporins
excellent against MSSA and streptococci, no activity against enterococcus, limited activity against gram negative, no activity against gram negative obligate anaerobes in the gut
first generation cephalosporins are excreted by the _____ unmetabolized
kidney
dose adjustments for first generation cephalosporins are made for patients with _____
poor kidney function
what are the second generation cephalosporins
cefaclor, cefuroxime, cefprozil
what second generation cephalosporins are PO
cefaclor, cefuroxime, cefprozil
what second generation cephalosporins are IV
cefuroxime
spectrum of activity for second generation cephalosporins
slightly less potent against gram positive, increased activity against gram negatives
given the spectrum of first generation cephalosporins, what are they good for
skin and skin structure infections, clean surgical procedures
given the spectrum of second generation cephalosporins, what are they good for
URTIs (bacterial sinusitis, otitis media), UTIs
the PO form of cefuroxime is a ____ that increases absorption by increasing lipophilicity
prodrug
______ possess a methoxy group at the 7-alpha position of the cephem ring instead of a carboxylic acid
cephamycins
what are the cephamycins
cefoxitin and cefotetan
cefoxitin and cefotetan possess ______ activity whereas other 2nd generation cephalosporins do not
gram-negative obligate anaerobic
_______ contains an N-methylthiotetrazole side chain (NMTT or 1-MTT) that can lead to inhibition of vitamin K epoxide reductase and increase prothrombin times and risk for bleed
cefotetan
if the cephamycins have anaerobic activity why are they not used in the setting of active infection where obligate anaerobes are present
due to resistance. so they are used for peri-operative prophylaxis
what are the third generation cephalosporins
cefotaxime, ceftriaxone, ceftazidime, cefpodoxime, cefixime, ceftibuten, cefdinir, cefditoren
spectrum for third generation cephalosporins
broad spectrum gram negative
the third generation cephalosporins are mostly excreted by the kidney except for ______ which undergoes enterohepatic recycling
ceftriaxone
therapeutic uses for third generation cephalosporins in the community
otitis media (recurrent/frequent), URTI
cefpodoxime PO form is a ______ that increases absorption by increasing lipophilicity
prodrug
bioavailability of cefpodoxime proxetil is ____
50%
what is different about ceftazidime
gram negative coverage includes pseudomonas aeruginosa
what is pseudomonas aeruginosa
nosocomial pathogen typically causing infections in hospitalized patients
