Glycopeptides Flashcards
Glycopeptides
Polypeptide agents- basic structural elements amino acids.
complex heterocyclic molecules with a heptapeptide backbone and various attached substituted sugars.
Inhibit cell wall synthesis which have a different target enzyme from B-lactams and no cross-resistance.
Active vs Gram +ves only. Too bulky to cross G-ve OM
Some G+ve genera are inherently resistant.
Vancomycin:
background mode of action pharmacokinetics pharmacodynamics spectrum of activity adverse effects
First isolated mid 1950s
Was then used to treat penicillin resistant staphylococci + other G+ves
Its usage dropped because of its toxicity and better options are emerging. Its use is now rising again because of emergence of resistant G +ves, especially MRSA. Staph aureus with decreased sensitivity is a problem.
Mode of Action:
Active in complexes with D-alanyl-D-ala of peptide precursor units.
It inhibits PG transglycosylation reaction –> inhibits 2nd stage of PG synthesis, at site earlier than penicillin site of action.
affects permeability of cell membrane.
may impair RNA synthesis.
Pharmacokinetics:
Poorly absorbed from GI
IV route used for parenteral admin
70-90% of IV dose excreted unchanged via kindeys.
oral route used for treatment of enterocolitis.
Pharmacodynamics.
concentration-independent killing occurs once concentration is greater than MBC, further increases in conc dont increase rate.
The time which conc exceeds MIC is most important pharmacodynamic principal in predicting efficacy.
postantibiotic effect duration is around 1.5-3hrs
Spectrum of activity.
bacterial endocarditis
bactericidal against coagulse -ve staphs, most S. aureus. bacillus species. only bacteriostatic against enterococci. resistance is a growing problem, especially in enterococci.
Adverse effects:
damage to auditory nerve
Red man syndrome, rash on neck and upper torso.
slow infusion is important
Teicoplanin
Naturally occuring, complex mix of closely related compounds sharing some structural & antimicrobial properties with vancomycin. restricted to G+ves can be injected intramuscularly. elimination of 40-70 hours MICs tend to be lower fewer adverse reacitions
Lipoglycopeptides (NEW)
eg. oritavancin, Dalbavancin, televancin
These contain lipophilic side-chain which aid in:
- prolonging half-life
- anchoring to cell membrane
- increasing activity against gram +ve cocci
recently approved in EU, UK US
Summary:
Glycopeptides and lipoglycopeptides used o treat some serious gram +ve infections.
Primary mode of action is to inhibit transglycosylation during PG synthesis
Lipoglycopeptides may also affect bacterial cell membrane.
