Cell Wall Synthesis Inhibitors Flashcards
Natural 1st Gen Penicillins
penicillin G, penicillin V
Penicillinase-Resistant 2nd Gen Penicillins
dicloxacillin, methicillin, nafcillin, oxacillin
Which 2nd Gen penicillin is never used for treatment?
methicillin, only clinical MRSA identification
Aminopenicillins 3rd Gen
amoxicillin, ampicillin
Extended Spectrum 4th Gen Penicillins
piperacillin, ticarcillin
Which penicillin do optometrists prescribe most?
amoxicillin
1st Gen Cephalosporins
cefadroxil, cefazolin, cephalexin
2nd Gen Cephalosporins (5)
cefaclor, cefotetan, cefoxitin, cefprozil, cefuroxime
3rd Gen Cephalosporins (8)
cefdinir, cefditoren, cefixime, cefotaxime, cefpodoxime, ceftazidime, ceftibuten, ceftriaxone
4th Gen Cephalosporins
cefepime
5th Gen Cephalosporins
ceftaroline, ceftolozane
What are the three beta-lactamase inhibitors used in antibiotic combos?
clavulanic acid, sulbactam, tazobactam
“Other” cell wall synthesis inhibitors…
bacitracin, daptomycin, telavancin, vancomycin
Why do antibiotics work?
selectively interfere with synthesis of bacterial cell wall which bacterial cells cannot live without and human cells do not possess
What do these antibiotics require?
a cell that is actively dividing (should not be combined with a bacteriostatic antibody)
What is the main difference between gram + and - bacteria?
(+) have cell wall most exterior (-) have outer lipopolysaccharide membrane in addition to cell wall
What two cell components do cell wall inhibitors target?
peptidoglycan and transpeptidase
What cell wall component do penicillins and cephalosporins target?
transpeptidase
What cell wall component do bacitracin and vancomycin target?
peptidoglycan
Penicillins are…
among the most widely effective and least toxic drugs known but have limited use due to increased resistance
What are penicillin drug difference attributed to?
side chains
What differences do side chains manifest?
antimicrobial spectrum, stability to stomach acid, cross-hypersensitivity, susceptibility to degradative enzymes
What is constant in antibiotic chemical structure?
the beta lactam ring
What are transpeptidase enzymes?
PBPs, a group of bacterial enzymes that are anchored in the cytoplasmic membrane and extend into the periplasmic space
What is the function of transpeptidase enzymes?
assembly, maintenance, and regulation of the peptidoglycan portion of the bacterial cell wall
What is the MOA of beta-lactam antibiotics?
form a covalent bond with transpeptidase and inhibit catalytic activity of these enzymes which prevents elongation and cross linking of peptidoglycan and leads to autolysis
T/F each bacterial species has a unique set of PBPs to which particular antibiotics bind
true
Penicillins easily cross the cell wall of…
gram (+) bacteria
“Easy to kill” gram (-) bacteria have…
proteins inserted to act as channels to allow entry of antibiotic
“Hard to kill” gram (-) bacteria have…
very restrictive porins and thus are resistant to many antibiotics including penicillin
Hard to kill gram (-) bacteria example
pseudomonas
Where are natural penicillins obtained from and what are they susceptible to?
obtained from mold fermentation, susceptible to inactivation by beta-lactamases
Of the two natural penicillins, which one is injected and more available systemically?
penicillin G
What are penicillinase-resistant penicillins used for?
use restricted to the treatment of infections caused by penicillinase-producing staph
What is important to remember about methicillin?
it is NOT used for treatment due to causing interstitial nephritis and is used only to identify resistant strains of S. aureus aka MRSA (methicillin resistant staph aureus)
What is used to treat MRSA?!
vancomycin!! because it is resistant to all beta-lactam antibiotics
What are extended spectrum penicillins used for? (aminopenicillins)
designed to maintain gram (+) coverage and add “easy” gram (-) coverage
What do optometrists usually prescribe?
amoxicillin (oral) + a penicillinase inhibitor
What are 4th gen extended-spectrum penicillins used for?
gram (-) coverage, aka antipseudomonal penicillins
What are the natural forms of bacterial resistance?
no cell wall, cell wall impermeable to the drug
What is the acquired form of bacterial resistance?
plasmid transfer of genetics for resistance to multiple agents
What are three acquired resistance properties?
beta-lactamase activity, decreased permeability and altered PBPs
Explain b-lactamase activity resistance
enzyme hydrolyzes the b-lactam ring of drug resulting in loss of bactericidal activity
Explain decreased permeability resistance
bacteria possess an efflux pump to push antibiotic back outside the cell
Explain altered PBPs
different PBPs have a lower affinity to antibiotics requiring a clinically unattainable concentration of the drug
Which form of acquired resistance does MRSA have?
altered PBPs
Describe the absorption of penicillins
most are incompletely absorbed after oral administration (some have only injection because of poor GI absorption)
Why do antibiotics affect intestinal flora?
they are incompletely absorbed and have sufficient quantities to affect flora
Which penicillin is almost completely absorbed?
amoxicillin
T/F penicillinase-resistant penicillins are destroyed in acidic environment
true
Why can’t you take penicillinase-resistant penicillins with food?
must be taken 30-60 minutes before or 2-3 hrs after because you cannot have an acidic stomach environment
T/F penicillins cross the placenta AND are teratogenic
false- they do cross the placenta but are NOT teratogenic
T/F penetration to bone or CSF is insufficient unless inflammation is also present
true
Is penicillin metabolism significant or insignificant?
insignificant
How are most penicillins excreted?
the kidneys
What percent of patients have hypersensitivity to penicillin?
5-10%
What are three signs of penicillin hypersensitivity?
rash, angioedema, anaphylaxis
T/F cross-allergic reactions with other beta-lactam antibiotics can happen
true, but rare… happens with 1st generation cephalosporins
What are adverse reactions to penicillins?
hypersensitivity, diarrhea, nephritis, neurotoxicity, hematologic toxicities
What is an important hematologic consideration with penicillin prescription?
penicillin causes decreased coagulation and should not be given to patients on a blood thinner (like warfarin)
T/F cephalosporins are closely related to penicillins and are also B-lactam antibiotics?
true
Cephalosporin MOA
the same as penicillin, cell wall synthesis disruption via transpeptidase
T/F cephalosporins tend to be more resistant to certain B-lactamases than penicillins are
true
First gen cephalosporins are used for…
gram positive coverage (including staph aureus)
Second gen cephalosporins are used for…
gram positive coverage, improved gram negative coverage, and anaerobic coverage ex: cefaclor or cefoxitin
Third gen cephalosporins are used for…
gram negative coverage (some pseudomonal coverage by ceftazidime)
Fourth gen cephalosporins are used for…
broad spectrum coverage, gram + and - with full Pseudomonas coverage but no anaerobic coverage (cefepime)
Fifth gen cephalosporins are used for…
gram negative and anaerobic with activity against S. aureus including MRSA (ceftaroline), S. pneumonia, and Pseudomonas (ceftolozane/tazobactim)
Which generation of cephalosporins are considered advanced?
5th gen
Which generation of cephalosporins have no oral formulations?
5th gen, injection only
What are the six basic uses of cephalosporins?
skin infections, intra-abdominal infections, pneumonia, serious infections, MRSA, pseudomonas
Which cephalosporin generation treats skin infections?
1st gen, gram (+)
Which cephalosporin generation treats intra-abdominal infections?
2nd gen, anaerobic
Which cephalosporin generation treats pneumonia?
3rd (or 4th)
Which cephalosporin generation treats serious infections (especially immunocompromised patients)?
4th gen
Which cephalosporin generation treats MRSA?
5th gen, ceftaroline
Which cephalosporins treat pseudomonas?
ceftazidime (3rd), cefepime (4th), ceftolozane (5th)
T/F cephalosporins are susceptible to staphylococcal penicillinase
false
T/F cephalosporins have poor oral absorption
true
What is true of the cephalosporin distribution?
only a few have penetration to CSF even if there is inflammation
Where are cephalosporins secreted from?
kidney, except ceftriaxone
Where is ceftriaxone eliminated?
liver/bile
What is the risk of cross-reactivity to penicillin?
1% chance with first generation, use generation 3 or later for patients with PCN allergy
What do B-lactamase inhibitors do?
do not have antibacterial activity themselves, blind to penicillinase and inactivate it to protect antibiotics
What are the three b-lactamase inhibitors?
clavulanic acid, sulbactam, tazobactam
What makes augmentin?
clavulanic acid and amoxicillin
What is vancomycin?
an “other” cell wall inhibitor effective against multiple drug resistant organisms aka MRSA
What is bacitracin?
an “other” cell wall inhibitor that causes nephrotoxicity and is only given topically as ointment (no oral/injection)
What is the MOA of vancomycin and bacitracin?
inhibits cell wall synthesis via peptidoglycan damaging the underlying cell membrane
What are vancomycin and bacitracin not effective against?
gram (-) cell wall synthesis
T/F vancomycin is restricted to treatment of serious infections
true, b/c plasma mediated resistance is developing
What is the administration of vancomycin?
slow IV infusion (oral only for enterocolitis)
What eliminates vancomycin from the body?
kidneys
What are the four adverse effects of vancomycin?
fever, chills, phlebitis at injection site, and flushing or shock
Why does flushing/shock happen with vancomycin and how can you prevent it?
happens if infusion is rapid due to rapid release of histamine, for prevention pre-treat with antihistamine
What is the synthetic derivative of vancomycin?
telavancin
What is telavancin used for?
alternative treatment for gram (+) infections, esp. skin
What is the MOA of telavancin?
inhibition of cell wall synthesis
What is the spectrum of telavancin?
used with gram (+) staph and strep including MRSA
T/F telavancin is more effective than vancomycin
false, it is the same not better
What are the pharmacokinetic considerations for telavancin?
hepatic metabolism uncertain, IV infusion, monitor renal function
What are adverse effects of telavancin?
taste disturbances, nausea, vomiting, insomnia, foamy urine, caution in cardiac conditions
T/F you can prescribe telavancin to pregnant women
FALSE
What is the MOA of bacitracin?
interferes with peptidoglycan and cell wall synthesis
Which bacteria, + or -, is bacitracin used for?
gram + coverage
T/F toxicity and allergic reactions are common with bacitracin
false
T/F bacitracin can be used during pregnancy
true
What is the administration of bacitracin?
topical only because of nephrotoxicity systemically
What medication is used mainly for infectious blepharitis and overnight coverage of bacterial corneal ulcers?
bacitracin
What is an alternative medication for treating gram (+) infections including MRSA?
daptomycin
What is the MOA of daptomycin?
induces rapid depolarization of cell membrane
What can daptomycin treat?
gram (+), skin structure infections
What inactivates daptomycin?
pulmonary surfactants, never use it for pneumonia
What are pharmokinetic considerations of daptomycin?
90 % bound to protein AND no hepatic metabolism
What are adverse effects of daptomycin?
constipation, nausea, headaches, myalgia, insomnia
