Antibiotics - Vancomycin/Macrolides

Question 1

What type of antibiotic is vancomycin

Answer 1

glycopeptide

Question 2

Vancomycin method of action

Answer 2

binds D-Ala-D-Ala and blocks transpeptidase

Question 3

Mutation which gives Vanc resistance

Answer 3

D-Ala-D-Lactate; 1000x less affinity

Question 4

Vanc spectrum

Answer 4

G+ bacteria NO G- or mycobacteria; particularly effective against staph/strep

Question 5

Vanc Resistance history tidbit

Answer 5

VRE came about due to antibiotics in european cow feed

Question 6

Vanc toxicities

Answer 6

red skin rash and potential anaphylaxis (rare)
nephrotoxicity and ototoxicity (rare)
just watch dosing

Question 7

Erythromycin ring description

Answer 7

14 member ring

Question 8

Polyketides are formed how? Which antibiotic?

Answer 8

sequential propionate groups (methyl groups on all alternating carbons); erythromycin

Question 9

Erythromycin is cidal or static

Answer 9

mainly static… cidal in high conc.

Question 10

Erythromycin has special delivery how?

Answer 10

accumulates in leukocytes so delivery to infection!!

Question 11

Erythromycin mechanism of action

Answer 11

bind reversibly to P site on 50S and inhibits translocation OR b/w P and A site to block peptide formation

Question 12

Erythro resistance occurs how

Answer 12

1) lactone ester hydrolase induced to degrade macrolides
2) RNA methylase blocks macrolide binding
3) adenine to guanine (10k affinity reduction)
4) efflux pump

Question 13

Erythronolide. What’s that all about?

Answer 13

starting molecule for synthesis

Question 14

Erythro doesn’t work on…

Answer 14

pseudomonas and enterobacter

Question 15

Erythro administration must be in what form? Why?

Answer 15

coated capsules or stable salts/esters as it is unstable in high acidity - forms ketals

Question 16

Macrolide acid stability achieved via…

Answer 16

1) 6-OCH3 derivative (actually clarithromycin) which increases oral absorption and block ketal formation at low pH
2) amine analog (actually Azithromycin) is also acid stable and reliable absorption; methyl amino replaces C-9 ketone

Question 17

Macrolides include

Answer 17

erythromycin clarithromycin azithrmycin

Question 18

Macrolide metabolism

Answer 18

mainly in liver via bile with some in urine; contraindicated in liver disease

Question 19

Erythromycin half life

Answer 19

1.5 hours

Question 20

Erythro and Clarithro inhibit…

Answer 20

CYP3A (dirithromycin doesn’t) (azithro doesn’t)

Question 21

DDI with erythro and clarithro?

Answer 21

hell yes…

Question 22

Macrolide side effects include

Answer 22

increased GI motility (vomit, cramp, ab pain)
skin reaction/hives
Stevens-Johnson and toxic epidermal necrolysis (rare)

Question 23

Extended macrolide use…

Answer 23

10-20 days give reversible cholestatic hepatitis w/ jaundice/cramp/nausea/fever

Question 24

Erythromycin in kiddos and millky moms

Answer 24

pyloric stenosis in kids

Question 25

lauryl sulfate prodrug of erythro

Answer 25

erythro estimate (more lipophilic which increases oral F); contraindicated in patients with liver disease; Tx GAS, 1* syphillis, amebic dysentery, surgery prophylaxis(endocarditis via viridians)

Question 26

ethyl succinate ester prodrug of erythro

Answer 26

erythro ethyl succinate (more lipophilic which increases oral F) flavored for kids

Question 27

Clarithromycin is better bc

Answer 27

blocks ketal formation (more stable in acid)
less side effects (due to ketals)
14 (R) metabolite has greater antibiotic activity than clarithromycin (esp against H. inf)

Question 28

Arithromycin is better bc

Answer 28

15 member ring - prevents metal formation (more stable in acid)
longer t1/2 (68 hours) compared to erythro (1.5hr)
conc is 50x higher in tissues than plasma
doesn’t give DDI like erythro and clarithro

Question 29

what stops azythro absorption

Answer 29

Mg and Al

Question 30

Azythro spectrum different how

Answer 30

more G- activity than erythro or clarithro