Polymyxins

Question 1

Polymyxins include 5 different chemical compounds but only 2 are used clinically:

Answer 1

B and E (colistin)

Question 2

Polymyxin structure

Answer 2

cationic polypeptide

Question 3

Polymyxin is an _____

Answer 3

amphiphilic molecule

Question 4

Polymyxin has a hydrophilic ____ and a hydrophobic ____

Answer 4

peptide ring; tail

Question 5

Polymyxin MOA

Answer 5

positively charge amino groups (L-Dab) align with lipopolysaccharide of Gram - and then hydrophobic tail interacts with bacterial cell membrane this causes increase in permeability of the cell wall and inner membrane allowing leakage of contents

Question 6

PolymyxinB oral absorption

Answer 6

nominal

Question 7

PolymyxinB 1/2 life

Answer 7

6 hours (long)

Question 8

PolymyxinB elimination

Answer 8

not renal

Question 9

Colistin oral absorption

Answer 9

nominal

Question 10

Colistin 1/2 life

Answer 10

1-3 hours; shorter

Question 11

Colistin elimination

Answer 11

renal

Question 12

Polymyxins are ____ dependent

Answer 12

concentration

Question 13

Polymyxins are bactericidal/bacteriostatic

Answer 13

bactericidal

Question 14

Colistin tissue penetration

Answer 14

poor into lung, pericardial fluid, and CSF

Question 15

inhaled colistin is used to optimize

Answer 15

lung exposure

Question 16

Conversion of CMS to colistin in kidneys causes

Answer 16

high urine concentrations

Question 17

Colistin is administered as

Answer 17

inactive prodrug (CMS)

Question 18

CMS is cleared by

Answer 18

renal excretion or converted to colistin (active agent)

Question 19

In patients with good renal function, CMS clearance is ____ than coversion leading to ____

Answer 19

faster; low serum concentrations

Question 20

Variables affecting colistin concentrations

Answer 20

batch to batch variability in composition of CMS

variability based on renal function

Question 21

Polymyxin B is administered

Answer 21

active form

Question 22

Polymyxin B has improved _____ over colistin

Answer 22

serum concentrations

Question 23

Polymyxin B is reabsorbed in the kidneys resulting in

Answer 23

low urinary concentrations of the agent

Question 24

CMS goes through mostly renal clearance and a small amount of other clearance this results in

Answer 24

high concentration of CMS and colistin in urine

Question 25

Left over CMS (that didn’t get renally cleared) conversion to colistin results in

Answer 25

largely Colistin clearance by other means and small % of colistin renally cleared

Question 26

Polymyxin B primary goes through

Answer 26

other clearance and small amount of renal clearance which results in low concentrations of it in the urine

Question 27

Polymyxins spectrum coverage

Answer 27

GRAM - ONLY
dark red: h. influenzae, E. coli, klebsiella, enterobacter, citrobacter, p. aeruginosa, acinetobacter

light red: m. cattarhalis

Misc: mycobacterium, not active against steno

Question 28

Polymyxins mechanisms of resistance

Answer 28

alterations of LPS
increase production of capsule polysaccharide
efflux pumps
increased levels of H1

Question 29

Polymyxins adverse effects

Answer 29

nephrotoxicity onset within 1 week and dose dependent (coadministration with other nephrotoxins may increase risk)

neuromuscular blockade

• dose dependent and reversible
• blocks release of acterylcholine
• weakness, paresthesia, ataxia

Question 30

Polymyxin B is considered _____ than colistin since

Answer 30

more reliable; administered in its active form

Question 31

Polymyxin B does/does not need renal adjustment

Answer 31

does not

Question 32

Colistin is preferred in treating

Answer 32

lower UTI

Question 33

Polymyxin B is preferred in treating

Answer 33

systemic use in invasive infections

Question 34

Polymyxin B are better used as

Answer 34

combination therapy