glycopeptides

Question 1

• group of antibiotics represented by natural occurring vancomycin and its semisynthetic analogues of telavancin, dalbavancin, oritavancin

Answer 1

glycopeptides

Question 2

glycopeptides core structure

Answer 2

• linear heptapeptide backbone connected to 5 aromatic rings
• rings provide rigidity
• D ring contains sugars

Question 3

glycopeptides MOA

Answer 3

• bacterial tail forms 5 h bonds w peptide backbone and prevents access to transglycolase enzyme

Question 4

• have long alkyl side chains in their sugar unit
• anchirs antiobitoic to bacterial cell wall
• enhances d ala d ala binding causing depolarization
• prolongs half life of dalbavancin

Answer 4

semi synthetic glycopeptides

Question 5

semi synthetic glycopeptides

Answer 5

• telavancin
• dalbavanin
• oritavancin

Question 6

• semi synthetic glycopeptide

- polar substituent in A ring improves water solubility but also decreases drugs half life

Answer 6

-Telavancin

Question 7

• semi synthetic glycopeptide

- amidation of free carboxyl group enhances activity against staphylococci including coagulase neg staph

Answer 7

• Dalbavancin

Question 8

• semi synthetic glycopeptide

- N alkyl p chlorophenylnezyl sub on sugar unit improving activity against enteroocci including VRSA and VRE

Answer 8

• Oritavancin

Question 9

• block addition of new nag-nam peptide subunit by binding directly to the 2 terminal D-ALA/D-ALA residue of the peptide chain referred to as polymerization
• mediated by transglycosylase, it cannot make anew bond and the nag nam cannot be insterted into cell wall

Answer 9

• glycopeptides

Question 10

what is the major diff between b lactams MOA and glycopeptides MOA?

Answer 10

• b lactams inhibit cross linking between 2 NAM units and involves transpeptidase
• GPs inhibit polymerization of NAG-NAM by binding D-ALA/D-ALA and inhibit transglyosylase activity

Question 11

• this GP not only decreases polymerization of NAG-NAM, but it also disrupts structure of bacterial cell membrane causing leakage of ATP and K and loss of potential
• bacteria’s dependent metabolic functions rapidly fail
• has “rapid kill” effect to decrease hospitalization time

Answer 11

• Telavancin (Vibativ)

Question 12

T or F

- glycopeptides are batericidal

Answer 12

True

Question 13

• Glycopeptides show activity against

Answer 13

• only gram pos aerobes including C. diff

Question 14

• glycopeptides antibiotic map

Answer 14

• enterococcus faecalis (+)
• S. pnuemoniae (+)
• strep pyogenes (+)
• MRSA and MSSA (++)`

Question 15

• MOA of VRE and VRSA to vancomycin

Answer 15

• altered binding sights: instead of D-ALA/D-ALA its replaced w D-ALA/D-lactase or D-set
• interspecies horizontal transfer of plasmid DNA

Question 16

• important ADME and PK of glycopeptides

Answer 16

• poor oral absorption, only use if treating C. Diff
• NOOOOO IM
• infuse at lest of 60 min
• if too fast leads to redmans syndrome**
• enters CSF if meninges inflamed
• dose adjustments required if renal issue in patient

Question 17

adverse effect of glycopeptides

Answer 17

• Infusion toxicity aka Redmans syndrome
• Ototoxicity
• Nephrotoxicity
• risk in pregnancy
• cardiovascular

Question 18

• structure is 13 AA of which 10 terminal residues form a ring, if it were 11 it woul dbe toxic
• ring attached to carbon fatty acid chain deconoic acid thorugh tripetide side chain
• amphipathic so soluble in water
• contains 1 cationoic and 3 anionic amino acids and exhibits net negative charge

Answer 18

• Lipopeptides (Daptomycin)

Question 19

MOA of daptomycin

Answer 19

• binds phospholipid bilayer of cell membrane in GRAM POS bacteria
• successful binding required calcium ions to form cationic DAAP-calcium complex
• DAP-Ca complex allows pore to form and leak ions which alters resting potential
• end result is shutdown of key metabolic path, nucleic acid and protein synthesis

Question 20

• most active against gram positive aerobic bacteria
• good activity against MRS and VRSA sometimes for VRE
• NOT active gains gram negs bc ccant penetrate outter membranes
• NOT active against anaerobes or atypical organisms

Answer 20

daptomycin

Question 21

daptomycin antibiotic map coverage

Answer 21

• note ALL gram pos
• VRE
• Enterococcus faecilis
• S. pnuemoniae
• strep pyogenes
• MSSA
• MRSA

Question 22

indications for daptomycin

Answer 22

• complicated skin and skin structure infections
• blood infections (bacteremia)
• soft tissue infection
• endocarditis has less success
• NOT good for lung infections b binds surfactant

Question 23

ADME of daptomycin

Answer 23

• only available IV
• 92% protein bound
• 1./day dosing and 8hr half life
• 80% eliminated in urine, dose adjust for renal insufficiency
• NO INTERACTION w CYP 450

Question 24

adverse rxn of daptomycin

Answer 24

• Injection sight rxns such as pain
• • rare eosinophilic pneumonia
• reversible myopathy at higher dose*****monitor CPK
• PNS disorder
• may DC in use w statins due to increase risk of myopathy

Question 25

• surface active agents
• amphipathic
• act against gram negs
• interact strongly w LPS endotoxin
• lipid A bonds to Ca and Mg
• positively charged
• disrupt inner membrane though hydrophobic interactions and cause ion/small molecule leakage

Answer 25

polymyxins

Question 26

polymyxins ADME and PK

Answer 26

• poor oral but some forms available
• salvage regimen in that last ditch effort to treat infections such as Psuedomonas
• often administered w Colistin IV route or inhalation
• need to dose adjust for renal insufficiency patients

Question 27

• Adverse effects of polymyxins

Answer 27

• high risk for neurotoxicity due to blockade of neuromuscular transmission
• muscle weakness
• apnea
• paresthesia
• nephrotoxicity (don’t use w aminoglycosides or loop diuretics)