Cell wall synthesis inhibitors Flashcards
What are the drug classes that are cell wall synthesis inhibitors?
What is the mechanism of action for penicillins?
interfere with formation of peptidoglycan layer and bacteriocidal
specifically bind to transpeptidase enzyme whose function cross-links NAM and NAG
What are the penicillin binding proteins activated by penicillins?
transpeptidases
autolysins
carboxypeptidases/endopeptidases
autolysisn is a penicillin binding protein. how does it work?
Carboxypeptidases/endopeptidases are PBPs. How do they work?
break peptide bonds
For penicillins to gain access to microbes, they must permeate the cell wall. What mechanisms of resistance do bacteria have for this?
Penicillins that are combined with bacteriostatic drugs. What happens?
antagonism results
synergistic actions are not expected
For penicillins to be effective inhibitors of cell wall synthesis, what must be taking place?
microbe must be actively growing and dividing
How do penicillins inhibit synthesis of bacterial cell walls? and what are the 2 results?
binding to penicillin binding proteins
- inhibits cell wall synthesis by blocking transpeptidation of peptidoglycan
- activates autolytic enzymes in cell wall that cause lesions resulting in bacterial cell death
What mechanism will allow bacteria to become resistant to penicillins?
actions of penicillins may be terminated by B-lactamase enzymes that reside in the periplasmic space
What can penicillin be combined with to get syngeristic actions?
penicillins + aminoglycosides
combo is a cell wall synthesis inhibitor plus a protein synthesis inhibitor
Why should antibiotics not be taken with oral contraceptives?
estrogens are recycled via the enterohepatic recirculation pathway and normally gut bacteria cleave estrogen-glucuronide allowing them to be reabsorbed
with antibioitcs, normal GI flora are disrupted that impairs enterohepatic recirculation of estrogenic compounds thus diminishing their half-life
use a backup for 7 days after finishing dose of antibiotics
What are the 4 distinct subclassifications of penicillins?
- natural penicillins
- aminopenicillins
- penicillinase-resistant penicillins
- antipseudomonal penicillins
What will coadministering penicillins with drugs that are irreversible inhibitors of B-lactamase do?
broaden the spectrum of coverage to include B-lactamase producing organisms
Which classes of penicillins are used to treat gram + microbes?
natural penicillins and penicillinase-resistant penicillins
Which classes of penicillins are used to treat gram (-) organisms?
aminopenicillins and antipseudomonal penicillins
What are the natural penicillins?
penicillin G and V
How should penicillin G be administered? why? and what indications are necessary?
administered via IV or IM because it is readily destroyed in acidic environments
treats rheumatic fever and syphilis
When should penicillin V be administered? How? What indications?
it is more stable so can be given orally
should be given on empty stomach, or 1 hour before meals, or 2-3 hours after meals
treats streptococcal pharyngitis
What drugs are amino penicillins?
ampicillin
amoxicillin
How should ampicillin be administered?
amoxicillin?
ampicillin can be orally given but best on empty stomach
amoxicilin can be taken w/ or w/o food b/c it is stable in presence of gastric acid
What are the penicillinase-resistant penicillins?
- dicloxacillin,
- methicillin,
- oxacillin,
- nafcillin
What is the mechanism of action of the penicillinase-resistant penicillins?
contain sie groups that protect the drugs from being inactivated by bacterial B-lactamases
Describe the different routes of administration for the penicillinase-resistant penicillins
methicillin, oxacillin, nafcillin => parenterally
dicloacillin => orally
What are the antipseudomonal penicllins (extended-spectrum)?
- carbenicillin
- ticarcillin
- mezlocillin
- piperacillin
How are the antipseudomonal penicillins usually administered? are there any exceptions?
parenterally
carbenicillin can be administered orally but therapeutic levels are only found in urinary tract
Carbenicillin is an antipseudomonal penicillin. What indications provide use for this?
urinary tract and prostatic infections
What are the irreversible inhibitors of B-lactamases?
clavulanic acid
sulbactam
tazobactam
what is important about the administration of the irreversible B-lactamase inhibitors?
they have NO antimicrobial activity by themselves
muse be combined with penicillins, expanded coverage against B-lactamase-producing microbes provided
Describe the cephalosporins structure and when they should be taken and how
cephalosporins resemble penicillins
they possess a B-lactam backbone
unlike natural penicillins, they are stable to pH changes and may be taken w/ or w/o food
If a patient has a penicllin allergy, would you prescribe cephalosporins?
no => possibility that penicillin-allergic patients may also be hypersensitive to cephalosporins
When cephalosporins are given orally, what is an adverse side effect? what if parenterally?
orally=> GI irritation but if taken with food then can be prevented
parenterally=> local irritation at site of injection
WRT excretion, what adverse effect of cephalosporins should be monitored?
since many are excreted by kidneys, renal toxicity is possible
caution for pre-existing renal disease or impaired creatinine clearance
2nd and 3rd generation cephalosporins may cause what adverse side effects? what if they are given parenterally?
disulfiram-like reactions and hyprothrombinemia
parenterally=> may cause seizures especially those with impaired kidney function due to accumulation
Cephalosporins disrupt normal flora. What is an adverse effect of this?
secondary infections
pseudomembrnaous colitis
vaginal yeast infections
What are the drugs considered carbapenums?
imipenem/cilastatin,
doripenem,
ertapenem
meropenem
What is the mechanism of action for the carbapenems? what is there structure and how does this help them?
bactericidial and inhibit cell wall synthesis
different stereochemical structure in B-lactam ring that renders them resistant to B-lactamases
What are some other antibiotics that dirupt cell walls?
- telavancin
- vancomycin
- cycloserine
- polymyxin B
What is the general mechanism of action for tevavancin and vancomycin?
interfere with cell wall synthesis by blocking polymerization and cross-linking of peptidoglycan by binding to D-Ala-D-Ala portion of cell wall
along with blocking polymerization and cross-linking of peptidoglycan by binding to D-Ala-D-Ala portion of the cell wall, what is the other mechanism in which televancin work?
disruption of membrane potential and changes in cell permeability because of presence of lipophilic side chain moiety
What is the mechanism of action for cycloserine? What organisms does it work for? What is it mainly used for?
inhibits cell wall synthesis in gram (+) and gram (-) microbes
reserved usually for treating Mycobacterium tuberculosis that are resistant to 1st-line antitubercular drugs
What is the mechanism of action for polymyxin B? What does it fight well?
cationic detergent that disrupts lipoproteins in bacterial cell walls to increase the membrane permeability
bactericidal to nearly all gram (-) bacilli (except proteus)
