Pharm - Penicillins & cell wall synth gen concepts Flashcards
name 3 glycopeptide antibiotics
are they beta lactams?
not beta lactams
vancomycin
telavancin
dalbavancin
name 4 “miscellaneous” AB’s
daptomycin
fosfomycin
bacitracin
polymyxin
name 3 “classes” of penicillins
G and V
B-lactamase resistant penicillins
extended spectrum penicillins
name 3 “extended spectrum” penicillins
amino, carboxy, ureido
name 5 beta lactam classes
penicillins
cephalosporins
monobactams
carbapenems
B-lactamase inhibitors
differentiate between gram positive and gram negative cell walls as far as peptidoglycan
gram positive has MANY more layers of peptidoglycan than gram negative
in gram negative, peptidoglycan layer is very thin
in gram positive cell walls, what binds the many layers of peptidoglycan together?
lipoteichoic acid
where is the penicillin binding protein located in bacteria?
is it in gram positive, gram negaitve, both?
on the cell membrane
in both gram pos and neg
which has porin channels and what do these do?
(gram pos or neg)
gram neg
controls entry into the bacteria
which can antibiotics enter more easily and why - gram positive or gram negative bacteria?
gram positive is easier to enter
it’s more porous
gram negative has a DOUBLE phospholipid membrane (outer and inner)
which has LPS - gram positive or negative
gram negative
compare the location of beta lactamases between gram pos vs gram neg
gram pos - outside the peptidoglycan layers
gram neg - most in the periplasmic space (btwn the 2 membranes) and some also in periplasmic space but trapped within the lipoproteins. –NOT outside the bacteria like in gram positive
peptidoglycan is composed of….
sugar + amino acids (peptides)
what enzyme do beta lactams like penicillins and cephalosporins block
transpeptidase - AKA PBP (penicillin binding protein)
explain what transpeptidase does
explain specific for staph aureus
enzyme involved in synthesizing cell wall peptidoglycan
forms a peptide cross bridge between 2 glycopeptide polymers via amino acid side chains. Specifically, in staph aureus, the bridge is (Gly)5-D-Ala between lysines. removes the last (5th) alanine and fuses the 4th onto the glycine of the other glycopeptide monomer
this reaction happens millions of times to form the cell wall
what is NAM
N-acetylmuramic acid
single sugar monomer (glycopeptide) that, along with NAG (N-acetyl glucosamine) forms the backbone for peptidoglycan
NAG + NAM are attached to….
a penta peptide (5 amino acids)
what are the terminal 2 amino acids in the glycopeptide polymer
D-ala D-ala
for cell wall synthesis to occur, it’s very important for PBP to bind…..
D-ala D-ala
explain the 3 “stages” of peptidoglycan/cell wall synthesis
- Make everything within the bacteria. racemierize and condense L-Ala to D-Ala with D-alanyl-D-alanine synthase
- Tranport outside of the membrane to start forming crossbridge
- Transglycosylation (fuse sugars) and transpeptidation (fuse amino acids) by PBP
what does D-alanyl-D-alanine synthase do and what inhibits it
racemerizes and condenses L-Ala into D-ala
inhibited by D-cycloserine (a medication)
Name 2 rings within penicillin
name 2 enzymes and their sites that can break down penicillin - RESISTANCE
4-membered beta lactam ring is fused to a thiazoline ring
beta lactam ring broken down by penicillinase/b lactamase
amidase is an enzyme that can destroy amide bond (O=C-N)
CN bond broken
penicillins and other beta lactams structurally resemble what?
D-alanyl D-alanine
(D-ala D-ala)
explain the MOA of penicillin
IRREVERSIBLY binds and inhibits PBP (transpeptidase enzyme) which forms a highly unstable penicilloyl-enzyme intermediate
true or false
penicillin reversibly binds PBP
FALSE
irreversibly with covalent bond
what does penicillin compete with
D-ala D-ala for PBP
true or false
all the beta lactams have the same MOA as penicillin
true
What penicillins CANNOT be hydrolyzed by staph beta lactamases?
are they active against MRSA?
antistaphylococcal penicillins like methicillin, nafcillin, oxacillin, and cloxacillin
NOT active against MRSA still
Penicillin V vs Penicillin G
Penicillin V given orally
Penicillin G given IV
name 2 things that penicillins (ie: pen g) are NOT active against
gram negative rods and staph aureus (resistance!! - b lactamases)
name what regular penicillins (like pen g) are active against
gram positives and gram negative cocci
NON-b-lactamase producing anaerobes
name 3 things that antistaphylococcal penicllins are active against
staphylococci (NOT MRSA)
streptococci
s. epidermis
true or false
penicillin G is active against staph
FALSE - staph is resistant through B-lactamases
only the antistaphylococcal penicillins are active against staph - BUT STILL NOT MRSA
name some things that antistaphylococcal penicillins are NOT active against
MRSA
enterococci
anaerobic
gram negatives
what are extended spectrum penicillins
like penicillin, but better against gram negatives - wider spectrum
true or false
extended spectrum penicillins are NOT active against staph
true
get hydrolyzed by beta lactamases
name 2 extended spectrum penicillins
aminopenicillins
antipseudomonal penicillins
4 mechanisms of penicillin resistance
what are the 2 main?
2 main:
-inactivation by B lactamases
-modification of target PBP’s
other 2:
-impaired penetration of the drug to target BPB (only gram - through porin channels)
-antibiotic efflux
name 2 ways that PBP is modified to give resistance
major - staph aureus modifies to PBP2a so penicillin can’t bind
other - pneumococcal and enterococci do same
**penicillinase acts on….
B lactam ring - breaks it
the penicillins differ in their ___ and ____
acid stability and protein binding
which 4 penicillins are acid-stable? what does this say about their route of administration?
Penicillin V
dicloxacillin
ampicillin
amoxicillin
given orally and relatively well absorbed
oral penicillins should be administered how in regard to food?
1-2 hours before or after a meal
which penicillin is usually given IV
Pen G
could also be given IM but it’s irritating and painful
true or false
penicillins are highly plasma protein (albumin) bound
TRUE
can displace other things
explain the distribution of penicillins
not well distributed to eyes and prostate and CNS
how is penicillin mainly excreted and why is this important
UNCHANGED (not lot of metabolism) in the kidneys
therefore, renal function is important consideration
route nafcillin and class
IV
anti-staphylococcal
route oxacillin and class
IV
anti-staphylococcal
route and class cloxacillin
PO
anti-staphylococcal
route and class dicloxacin
PO
anti-staphylococcal
route penV
oral
route and class amoxicillin
PO
extended-spectrum penicillin
(same as augmentin)
route and class pipercillin
IV
extended spectrum penicillin
route and class ticarcillin
IV
extended spectrum penicillin
as mentioned, penicillins are weakly distributed to the CNS. Therefore, can they be used for meningitis
they actually can - bc in meningitis the meninges are kind of “leaky” so they can still get in
name 2 IM penicillin injections and rationalize the ingredients
benzathine penicillin - benzathine is a stabilizer for IM injection
procaine penicillin G - procaine is anesthetic for IM injection to help with the pain
DEPOT
benzathine penicillin and procaine penicillin G is effective treatment for….
B-hemolytic streptococcal pharyngitis
(STREP THROAT)
penicillin is synergistic with which 2 drugs
gentamicin and tobramycin
_______ is really only indicated for minor infections (like simple respiratory inf or minor SSTI) because of relatively poor bioavailability
penicillin V
name 3 anti-staphylococcal penicillins
which strain are they specifically used to treat
nafcillin
cloxacillin
dicloxicillin
ONLY MSSA
penicillinase-producing staphylococci - they are resistant to the B lactamase they produce and can survive
as mentioned, nafcillin, cloxacillin, and dicloxacillin can be used to treat MSSA and penicillinase producing staphylococci
name their routes of administration as a recap
nafcillin - IV
cloxacillin and dicloxacillin - PO
name the aminopenicillins and their general common feature
which is better absorbed?
how do their spectrums of activity differ?
ampicillin and amoxicillin
they are stable orally!!!!
amox is better orally absorbed
both have similar spectrum
explain what kind of infections amox/ampicillin can and CANT be used for
can - UTI, lowerrespiratory tract, sinusitis, otitis, meningitis, speticemia
NOT - for common nosocomial infections like pseudomonas, enterobacter, and klebsiella
what is calvulanic acid
beta lactamase inhibitor often combined with amoxicillin
chemical name for the “extended spectrum” penicillins
carboxypenicillins AND ureidopenicillins
example of ureidopenicillin and route administration
pipercillin
IM/IV
what can pipercillin be combined with
a beta lactamase inhibitor to increase activity
ie- TAZOBACTAM, sulbactam, clavulanic acid
explain what pipercillin is active against
lot of gram negatives
MAINLY - PSEUDOMONAS (NOSOCOMIAL) and klebesiella
anti-pseudomonial penicillins
extended spectrum
carboxy penicillins - like ticarcillin
ureido penicillins - like pipercillin
name a carboxypencillin as well as route administration
ticercillin IV/IM
ticarcillin is given in combo with…..
clavulanate
briefly explain what ticarcillin can be used for
more serious infections - like bacteremia, pseudomonas, bone and joint infections, SSTI, UTI, gynecologic infections, intra-abdominal infections, lower resp
carboxypenicillins are NOT used for ___ and ___
gram positive cocci and listeria
can ampicillin be combined with a beta lactamase inhibitor
YES
side effects penicillin
well tolerated generally
obviously - risk of hypersensitivity and anaphylaxis (less than 1%) which could progress to shock
SEIZURES in renal failure pts – only for high doses – we must lower the dose for them!!!
HOW does penicillin cause hypersensitivity in some patients
the degradation products of penicillin like penicilloic acid and products of alkaline hydrolysis bind the host protein
which penicillin can cause neutropenia
nafcillin
which penicillin can cause interstitial nephritis
methicillin
which penicillin can cause hepatitis
oxacillin
NVD from penicillins is most common when
either broad spectrum or high doses – killing all the good
_____- can cause pseudomembranous colitis and vaginal candidiasis
ampicillin
3 DDIS of PEN G and PEN V
decrease effectiveness oral contraceptives
probenecid increases plasma levels
colestipol decreases PEN V (oral) absorption
are penicillins bactericidal or static
CIDAL
