Vancomycin

Question 1

Vancomycin MOA

Answer 1

-inhibits cell wall synthesis by binding D-alanyl-D-alanine portion of cell wall precursors
= prevents cross-linking and further elongation of peptidoglycan strucutre
= weakens cell wall
=lysis (bactericidal)

Question 1

Vancomycin targets

Answer 1

-gram + pathogens
-MRSA, stept, listeria
-high resistance in enterococcus f
-c. diff give orally bc GI infection

Question 2

Vancomycin adverse effects

Answer 2

-nephrotoxicity/ototoxicity
-infusion issues (histamine release)
-local phlebitis
-hypersensitivity, Stevens Johnson Syndrome
-Thrombocytopenia (prolonged admin)

Question 3

Vancomycin PK

Answer 3

-poorly absorbed PO
-must admin IV for systemic infections (NOT IM)
-longer distributions phase (1-2 hours)
-Vd = 0.7 L/kg
-50% protein binding
-renal elimination
-6-12h t1/2
-removed by high-flux hemodialysis (10%/h, admin dose after dialysis on dialysis days)

Question 4

Vancomycin PD

Answer 4

-time-dependent activity
-PD target: Auc/MIC
-goal AUC/MIC= 400-600mg*h/L (assuming MIC of 1mcg/mL)

Question 5

elevated AUC of vancomycin

Answer 5

-AUC >600-700mg*h/L
-prolonged is risk factor for nephrotoxicity
-high AUC during first 48 hours inc risk 3-4x

Question 6

Vancomycin loading dose

Answer 6

-20-35mg/kg based on total body weight in critically ill pt
-do not exceed 3000mg
-25mg/kg is good dose

Question 7

Vancomycin maintenance dose

Answer 7

-15-20mg/kg q8-12h based on total BW in pt with NORMAL renal function

Question 8

Vancomycin max infusion rate

Answer 8

-10-15mg/min

-1000mg takes about an hour
-2000mg takes about 2 hours

-some might need slower

Question 9

Vancomycin dosing interval

Answer 9

-dependent on renal function CrCL

Question 10

Loading dose

Answer 10

-useful to rapidly achieve targeted serum concentrations and dec risk of subtherapeutic concentrations
-pt do NOT achieve SS faster!! that shit is dependent on half life!!

Question 11

Loading dose recommended for

Answer 11

-critically ill/ICU
-dialysis/renal replacemnt therapy
-initiating continuous infusion dosing

Question 12

Vancomycin intitial dosing intervals based on CrCl

Answer 12

-120: 12
-100:12-18
-80: 18
-60: 24
-40: 36
-20: 60

Question 13

Vancomycin Vd=

Answer 13

0.7L/kg

Question 14

Vancomycin maintenance dosing

Answer 14

-15-20mg/kg using TBW
-15 if 120-200kg, use 0.6L/kg Vd
-q8-12h if <30 and >100ml/min CrCl
-12-18h if >60
-q24 for 40-49
-q36-48h 25-39
-intermittent is <25
-consider q8h for pt w fast drug clearance: cystic fibrosis, thermal burn injury, trauma, IV drug users

Question 15

Vancomycin monitoring

Answer 15

-AUC/MIC over 24 h = 400-600
-maintain trough concentrations > 10mcg/mL

Question 16

Vancomycin loading dose

Answer 16

-20-35mg/kg ABW
-max 3000mg

Question 17

Vancomycin monitoring methods (2)

Answer 17

-obtain 2 concentrations at or near Css (peak around 1-2 hours after infusion)
-SAWCHUK-ZASKE FIRST ORDER to determine AUC and optimal dose
-use BAYESIAN software and obtain 1-2 concentration with at least one trough
-preferred: 2 samples shortly after and right before end of interval (pt doesnt have to be at Css)

Question 18

Two compartment model

Answer 18

-inc during infusion
-distribution, elimination

Question 19

Initial dosing using population parameters

Answer 19

1. select desired Cmax and Cmin to achieve target AUC
2. calc IBW, AdjBW, LBW prn
3. estimate CrCl (Cockcroft-Gault)
4. estimate elimination (k)
5. half-life
6. Vd
7. tau
8. MD to nearest 250mg
9. double check
10. AUC

Question 19

Initial vancomycin dosing in practice

Answer 19

-dose based on mg/kg and interval on CrCl
-or
-population dosing to calc INITIAL regimen

Question 20

Cmax, Cmin targets

Answer 20

-30-35 mcg/mL
-10-15 mcg/mL

Question 21

use adjBW in vancomycin when

Answer 21

-TBW >1.3IBW
-use LBW if obese (BMI>40)

Question 22

Cockroft-gault

Answer 22

-estimates CrCl
-if TBW < IBW use TBW
-LBW if obese
-CR comes from. muscle, need good estimate of lean mass

Question 23

Sawchuk-Zaske Method

Answer 23

1. verify

Question 24

when to begin new infusion regimen

Answer 24

t equation
-number of hours to wait from PEAK to beginning new regimen
-on the hour no half hour

Question 25

Continuous Infusion (CI) dosing

Answer 25

-Ci is reasonable alt
-simililar/reduced risk of nephrotoxicity
-LD: 15-20 mg/kg
-MD: 30-40 mg/kg up to 60mg/kg
-Css 20-25mcg/mL
-need dedicated IV line
-fewer blood samples, obtain blood sample at any time
-more rapid attainment of desired concentrations

Question 26

24 hour dose of CI dosing

Answer 26

-24h dose = desired AUC24 by Cl (v*k)