Antibiotics 2 - Vancomycin and Macrolides Flashcards Preview

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Flashcards in Antibiotics 2 - Vancomycin and Macrolides Deck (54)
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1

Vancomycin is what type of compound

Glycopeptide

2

Vancomycin is an inhibitor of...

Gram+ cell wall biosynthesis

 

*BInding of the peptidyl side chain D-ala-D-ala in the peptidoglycan precursor

**Inhibits the transpeptidation required for PG crosslinking

3

Vancomycin effects and spectrum

Bactericidal, effective against Gram + bacteria

 

4

What is the threshold for a "susceptible strain" in Vancomycin treatment? 

 

Staph strains that are methicillin resistant are usually inhibited with...

MIC of 4 μ/mL

 

...with MIC of 1-5 μ/mL

5

VRE is connected to the use of ____

Avoparcin

(a glycopeptide AB)

6

Mechanism of resistance (VRE)

Mutation in precursor to PG cell wall

 

D-ala-D-ala --> D-ala-D-lactate

 

(1000x less affinity for the lactate one)

7

Vancomycin potential sides (3)

Hypersensitivity response

Nephrotoxicity (.1-1%)

Ototoxicity (rare)

 

8

Macrolide AB's are ________

and _______

Macrocyclic lactones

Polyketides (sequential addn of proprionate groups to a growing chain)

9

Macrolide site of protonation

The N on the desosamine sugar

10

Production of Erythromycin

Propriony-CoA 

(saccharopolyspora erythrea)

Erythronolide

(Converge with deoxyheose)

Erythromycin

11

pHa of the amine in erythromycin

8.8

 

12

The amine in erythromycin can form salts that are more soluble, including ___ and ____

Glucoheptonic acid

Lactobiononic acid

13

During peptide bond formation (transpeptidation), the polypeptide attached to the tRNA in the ____ is transferred to _____

polypeptide in the P site is transferred to the amino group of the aminoacyl-tRNA in the A site

14

Macrolides inhibit protein synthesis by binding _______

irreversibly to the P site -- inhibiting the translocation from A to P

15

Macrolide binding involves the bacterial _____ and not _____

the bacterial 23S RNA and not the protein

16

Macrolide may be _____ or _____ depending on _______

bacteriostatic 

bactericidal

concentration

 

17

Macrolides accumulate within ______

leukocytes

 

*transported to site of infection

18

Four mechanisms of macrolide resistance:

  1. Induction of lactone ester hydrolase (degrades by hydrolysis)
  2. Drug induced production of RNA methylase (methylated A2058 prevents eryth from binding to 50S)
  3. Adenine-> Guanine at A2058 (same as above)
  4. Efflux pump (active transport)

19

Resistance management for macrolides is especially important in regards to...

respiratory infections

20

Intrinsic macrolide resistance organisms

Pseudomonas

Enterobacter

21

Acidic inactivation of the parent molecule (macrolide) is a formation of _________________

intramolecular acid-catalyzed ketal formation

22

Oral erythromycin is administered as ____ or ______

enteric coated tablets or more stable salts or esters

23

(Macrolide) Acid stability can be achieved with the ______

6-OCH3 derivative

 

=blocks ketal formation at low pH

--> enhances oral absorption

**this is CLARITHROMYCIN

24

Amine analog that is acid stable

Azithromycin

25

Azithromycin structural difference

N-methylated methylene-amino moiety replaces the C9 ketone

26

Main route of erythromycin metabolism

demethylation in the liver

 

---> main elimination route is in the bile

27

Erythromycin half life

1.5 hours

28

DDI for Erythromycin and clarithromycin

Lower DDI drug?

They bind and inhibit 3A4

 

Dirithromycin has reduced capacity to inhibit p450's

 

29

Drugs that interact with macrolides

  • Carbamazepine
  • Cyclosporin
  • Disopyramide
  • Midazolam
  • Quinidine
  • Rifampacin
  • Rifabutin
  • Theophylline
  • Triazolam
  • Zidovudine

30

___ and ____ reduce the activity of erythromycin

rifampacin

rifabutin