Erdman AG

Question 1

T/F: AG are non-polar compounds

Answer 1

FALSE: they are very polar compounds that are polycationic, highly soluble in water, and incapable of crossing the lipid-containing cellular membranes

Question 2

MOA of AG

Answer 2

inhibition of protein synthesis through irreversibly binding to 30S (some 50S) ribosomal subunits

leads to disruption of initiation of protein synthesis, measurable decrease in protein synthesis, and misreading of mRNA

Question 3

Step wise process of AG activity in gram (-) bacteria

Answer 3

1. bind to and diffuse through extracellular membrane (porins)
2. once in periplasmic space, must transport across the cytoplasmic membrane
3. AG bind to polysomes and inhibit the synthesis of proteins
4. this disrupts the structure of the cytoplasmic membrane which accelerates AG entry into the cell

Question 4

AG display ________ activity in a _____________ dependent manner

Answer 4

rapidly bactericidal; concentration

** static against enterococcus **

Question 5

MOR of AG resistance (3)

Answer 5

Alteration in AG uptake
Synthesis of AG-modifying enzymes
Alteration in ribosomal binding site

Question 6

Alteration in AG uptake is?

Answer 6

MOR in which a chromosomal mutation takes place that influences either the binding to and/or the electrochemical gradient that facilitates AG uptake

Question 7

Synthesis of AG-modifying enzymes is?

Answer 7

a plasmid-mediated MOR that enables resistant bacteria (gram -) to modify the structure of AG through acetylation, adenylation, or phosphorylation (causes HIGH LEVEL RESISTANCE)

Question 8

T/F: cross resistance occurs within all AG abx

Answer 8

FALSE: Gentamicin and tobramycin generally affected by same enzymes, but amikacin is generally unaffected

Question 9

T/F: Alteration in ribosomal binding sites is a common MOR

Answer 9

FALSE: rarely occurs for A,G,T due to multiple binding sites. Common in streptomycin only as it only has a single binding site

Question 10

AG clinical efficacy correlates with ____:MIC ration

Answer 10

PEAK (10-20:1 ratio)

Question 11

T/F: AG should never be used as monotherapy for gram(+) bacteria

Answer 11

TRUE: should only be used in combination with cell wall active abx (vanc., B-lactams, etc.)

primarily gent used

Question 12

Which gram (+) are covered

Answer 12

viridans strep.
enterococcus spp. (gent/strep)
s. aureus**** and coag (-) staph

Question 13

Which AG are highly active against gram (-) aerobes

Answer 13

Gent, tobra, and amik (A>T>G)

• COVERS P. AERUGINOSA*
• often used in combination with cell wall active agents)

Question 14

T/F: Higher doses of AG are used with gram (+) infections than with gram (-)

Answer 14

FALSE: reverse is true

Question 15

Which AG cover tuberculosis caused by mycobacteria

Answer 15

Streptomycin and Amikacin

Question 16

What bacteria do AG have a PAE for

Answer 16

gram (-) finite PAE (2-4 hours)

Question 17

Synergy exists between…?

Answer 17

AG and cell wall active agents

thought to be due to enhanced uptake of AG due to damage done to cell wall

Question 18

synergy has been demonstrated for

Answer 18

entercoccus (gent/strep)
s. aureus & viridans (gent)
P. aeruginosa and other gram (-) (G,T,A)

Question 19

What characteristic of AG accounts for their lack of absorption orally, pattern of distribution, and elimination as unchanged drug in the urine

Answer 19

the fact that they are highly polar cations

Question 20

T/F: AG do not display interpatient variability

Answer 20

FALSE: display in the PK parameters of VD and CL - which directly influences dosing

Question 21

T/F: All methods of admin are equally effective

Answer 21

False:
poor oral absorption
IM has good absorption (peak 30-120 min after inf)
IV - preferred route - intermittent infusion

Question 22

T/F: IM infusion of AG should not be used in critically ill patients

Answer 22

TRUE

Question 23

AG are primarily distributed into……

Answer 23

ECF

Question 24

AG are distributed poorly into…..

Answer 24

CSF, sputum and adipose tissue

Question 25

______ body weight should be used for calculating AG dose

Answer 25

Lean **use adjusted for obese patients >130% LBW

Question 26

T/F: volume differences of hospitalized/pt. w/ certain medical conditions do not need to be taken into account when calculating dosing of AG

Answer 26

False: must be taken into account and must reach therapeutic concentration (in a timely manner) as they are concentration dependent killers

Question 27

AG are eliminated?

Answer 27

renally - 85-95% eliminated unchanged in the urine

Question 28

How does decreased renal function influence half life of AG

Answer 28

directly correlate with the elimination in the form of prolonged half-life

Question 29

T/F: AG need to be supplemented after dialysis

Answer 29

TRUE

Question 30

T/F: Serum concentration need only be monitored in patients with decreased renal function when receiving AG treatment

Answer 30

FALSE: MONITOR IN ALL PATIENTS - due to interpatient variability in PK parameters and the narrow therapeutic index

Question 31

When treating patients with gram (-) sepsis it is imperative to __________ within 24 hours. Why?

Answer 31

therapeutic concentration; increased mortality in these patients

Question 32

Standard dosing is determined by

Answer 32

LD: patient's renal function, subsequent doses by peak and trough levels

Question 33

Once-daily (extended interval) dosing should only be done in patients with ____?

Answer 33

normal renal function, normal Vd, and in tx of urosepsis, intraabdominal infections, and skin/soft tissue infections

Question 34

``` Gentamicin desired peak levels in (traditional dosing) gram (-) Mild - Moderate - Severe - ``` gram synergy (+) -

Answer 34

gram (-) 4-6 6-8 8-10 gram (+) 3-5

Question 35

``` Gentamicin desired trough levels in (traditional dosing) gram (-) Mild - Moderate - Severe - ``` gram synergy (+) -

Answer 35

gram (-) 0.5-1.5 1-1.5 <2 gram (+) 1

Question 36

dosing for once-daily dosing of AG

Answer 36

5-7 mg/kg/dose

Question 37

dosing for traditional dosing of AG

Answer 37

1-2.5 mg/kg/dose

Question 38

T/F: Institutions never use extended interval dosing in patients with CrCl <40-50

Answer 38

FALSE: some institutions do but extend the interval from 24 hr to 36/48 hours

Question 39

In extended interval dosing subsequent dosing is based on?

Answer 39

serum concentrations taken 2 and 10 hours after the end of the infusion oOR using the Hartford nomogram with a serum concentration drawn 8-12 hours after first dose

Question 40

Desired peak and trough levels from extended interval dosing

Answer 40

peak: 13-20 trough: <0.5 **rarely obtained in once-daily/extended interval

Question 41

T/F: AG are rarely used alone

Answer 41

TRUE

Question 42

Which AG are used for treatment of serious gram (-) aerobic bacteria (including P. aeruginosa)

Answer 42

Amik, Gent, Tobra

Question 43

Which AG are used in combo with cell wall active agents for treatment of gram (+) bacteria

Answer 43

gent and strep

Question 44

Which two AG are used in the tx of tuberculosis

Answer 44

Amikacin and streptomycin

Question 45

Most common side effects

Answer 45

nephrotoxicity & Ototoxicty

Question 46

T/F: nephrotoxicity is irreversible if caused by AG

Answer 46

False: if caught early enough it is reversible

Question 47

What are the risk factors for nephrotoxicity

Answer 47

prolonged high trough concetrations, prolonged therapy >2 weeks, presence of underlying renal insufficiency

Question 48

T/F: Ototoxicity damage is irreversible

Answer 48

True- must be caught early to prevent detrimental loss same risk factors as nephrotox

Question 49

what rare ADE is seen with neomycin

Answer 49

neuromuscular blockade