Antibiotics 4.1 - Streptogramins and Oxazolidinones Flashcards Preview

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Flashcards in Antibiotics 4.1 - Streptogramins and Oxazolidinones Deck (33):
1

Streptogramins are a ___ derivatives of a natural mixture of ____ and _____.

 

(Isolated from?)

Semisynthetic derivatives of Pristinamycin I and II

 

Isolated from Streptomyces pristinaspiralis

2

Synercid combo = 

30% Quinupristin

70% Dalfopristin

3

Quinupristin and Dalfopristin have side chains that...

Have amino side chains that allow salt formation

 

(Enhance water solubility)

4

Each (Quin/Dalf) given alone is ______, but when given together are ________.

Each is bacteriostatic, but together are bactericidal

5

Dalfopristin MOA

Directly interferes with the peptidyl transferase-catalyzed step.

 

(PT = Formation of bond between two amino acids, while breaking the bond between the fmet and its tRNA)

6

Quinupristin MOA

Binds in the ribosomal tunnel and causes blockage in the tunnel.

 

7

Binding of Quin/Dalf results in...

a very stable ternary dalfo-quinu-ribosome complex 

 

(1:1:1 stoichiometry)

8

Dalfo and Quinu bind to the _____ within the ribosome

23S rRNA

9

Mutation in _____, which gates the exit tunnel, confers resistance to ______

A2062

Streptogramin

10

Synercid uses

  1. VREf (Vanc resistant E. faecium)
  2. MRSA (cutaneous)
  3. VREf UTIs

11

Most common resistance to quinupristin

adenine methylation of A2058 in 23S rRNA

 

(as in erythro+clinda)

12

In addition to methylation of A2058, restistance to streptogramins can also be due to...

efflux + enzymatic inactivation

13

Cure rate of VREf by Streptogramins

70%

14

Streptogramin reserved for serious life threatening infctns caused by _____

Gram positives

15

What is virginiamycin

Streptogramin that is used in animal feeds

 

increases the indicience of AB resistance

16

Average Streptogramin T1/2

1.5 hrs in serum

 

(linear relationship between dose and AUC)

17

BBB penetration in Streptogramin

N/A

18

Macrophage Streptogramin PK's?

Concentrate the drug up to 50X the ECF concentration

19

Clearance of Streptogramin is _______

75% biliary

 

(remainder = renal)

20

DDI for Streptogramin

Inhibit CYP3A4

(warfarin, diazepam, astemizole, terfenadine, cisapride, NNRTI's, cyclosporine)

21

Oxazolidinones compounds

Linezolid (available)

Eperezolid (experimental)

22

What separates linezolid in terms of MOA?

Interacts with 50S subunit (with micromolar affinity)

--> Prevents formation of the 70S initiation complex

 

*most AB's inhibit protein synthesis at the elongation stage

23

Linezolid interacts specifically with _____

23S rRNA

24

Linezolid is used to treat: (3)

  1. VREf
  2. Nosocomial MRSA's
  3. Cutaneous MRSA's

25

Linezolid ROA's

Oral (high BA) and I.V.

26

Important consideration when choosing Linezolid as a treatment

Should only be used to treat of prevent infections that are proven or strongly suspected to be caused by multiple drug-resistant Gram+ bacteria

27

Linezolid resistance organisms

MRSA, E.coli, others

28

Linezolid mechanism of resistance

Target site modification = reduced affinity of linezolid to the 50S subunit

 

G->U mutation in Peptidyltransferase at position 2576

29

Most common Linezolid sides

N/V/D

also headache, tongue discoloration and oral Candida

30

Long term use of Linezolid sides (2)

Myelosuppression

Neuropathy

31

BA and Half life of Linezolid oral

100% BA

4-6 hrs T1/2

32

Linezolid effect on P450

Neither an inducer nor an inhibitor

33

Linezolid effect on MAO

Reversible nonselective inhibitor of MAO

 

DDI with serotonergic or adrenergic agents

(--> avoid tyramine)