Antibiotics 2 - Vancomycin and Macrolides Flashcards Preview

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

31

Other drugs that can have DDIs with macrolides

ergotamine

digoxin

methylprednisone

32

14-membered macrolides stimulate ______

GI motor activity

33

Serious allergic/immune responses from macrolides include ___ and ____

Steven-Johnson syndrome 

Toxic epidermal necrolysis

34

Long term macrolide use can induce...

reversible cholestateic hepatitis

35

Erythromycin can increase the probability of ____ in kids whose mothers took the med during pregnancy or breastfeeding

pyloric stenosis

36

Erythromycin is inactivated by gastric acids, so all formulations are...

given as enteric coated capsules

37

Erythromycin is rapidly absorbed and accumulates in high concentrations within...

phagocytes

38

During active ____, large amounts of Erythromycin are released

phagocytosis

39

the propionyl ester, lauryl sulfate prodrug of erythromycin

Erythromycin estolate

40

2 functions of the propionyl ester group in erythromycin estolate

  • makes the drug more lipophilic than erythromycin itself
  • increases oral absorption and blood levels of erythromycin after oral administration

41

Pathophys of the erythromycin induced Cholestatic jaundice

  1. The bile becomes granular in the bile duct
  2. Granules impedes bile flow
  3. Bile salts back up into the circulation

 

42

What must you do if a patient develops cholestatic jaundice while being given erythromycin

drug must be replaced by a nonmacrolide antibiotic

43

Erythromycin estolate is contraindicated in

patients with preexisting liver disease or dysfunction

44

Erythromycin Estolate is used to treat... (4)

  • Beta hemolyric strep
  • Primary siphilis
    • amebic dysentery
  • Viridans endocarditis prophylaxis

45

Erythromycin Ethyl Succinate 

  • It is a ______
  • It is more ______ than erythromycin
  • It is used as a ________

  • It's an ethyl succinate ester prodrug
  • It is more lipophilic and orally available
  • it is used as flavored oral suspension for kids

46

Clarithromycin is the ________ of erythromycin

What does this do?

 

 the C-6 methyl ether of erythromycin

It blocks ketal formation and makes it more stabile in acid

47

Clarithromycin results in ________ due to reduction of ketals

reduced gastric upset

 

(gastric upset is usually caused by ketal degradation products)

48

Clarith forms a _____ compound

Which is especially good against _____

14-(R)-Hydroxy  metabolite

 

H. influenzae

49

Structure of azith: its a ____ ring (why?)

15 membered lactone ring

 

because an N-CH3 group has been inserted between C9 and C10, and the carbonyl Oxygen has been removed

50

Azith half life compared to eryth

Longer - terminal half life 68 hours

51

Magnesium / aluminum and Azithromycin?

Forms coordination complexes - prevents absorption

52

Major route of elimiation of azithromycin

53

Azithromycin has a greater activity against ____ than erythromycin or clarithromycin

Gram negatives

54

Most common side effects of azith

Diarrhea, nausea, abd. pain