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PHRM 865 EXAM2 > Erdman AG > Flashcards

Erdman AG Flashcards

1
Q

T/F: AG are non-polar compounds

A

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

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2
Q

MOA of AG

A

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

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3
Q

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

A
  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
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4
Q

AG display ________ activity in a _____________ dependent manner

A

rapidly bactericidal; concentration

** static against enterococcus **

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5
Q

MOR of AG resistance (3)

A

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

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6
Q

Alteration in AG uptake is?

A

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

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7
Q

Synthesis of AG-modifying enzymes is?

A

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

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8
Q

T/F: cross resistance occurs within all AG abx

A

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

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9
Q

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

A

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

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10
Q

AG clinical efficacy correlates with ____:MIC ration

A

PEAK (10-20:1 ratio)

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11
Q

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

A

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

primarily gent used

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12
Q

Which gram (+) are covered

A

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

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13
Q

Which AG are highly active against gram (-) aerobes

A

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

  • COVERS P. AERUGINOSA*
  • often used in combination with cell wall active agents)
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14
Q

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

A

FALSE: reverse is true

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15
Q

Which AG cover tuberculosis caused by mycobacteria

A

Streptomycin and Amikacin

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16
Q

What bacteria do AG have a PAE for

A

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

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17
Q

Synergy exists between…?

A

AG and cell wall active agents

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

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18
Q

synergy has been demonstrated for

A

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

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19
Q

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

A

the fact that they are highly polar cations

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20
Q

T/F: AG do not display interpatient variability

A

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

21
Q

T/F: All methods of admin are equally effective

A

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

22
Q

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

A

TRUE

23
Q

AG are primarily distributed into……

A

ECF

24
Q

AG are distributed poorly into…..

A

CSF, sputum and adipose tissue

25
Q

______ body weight should be used for calculating AG dose

A

Lean

**use adjusted for obese patients >130% LBW

26
Q

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

A

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

27
Q

AG are eliminated?

A

renally - 85-95% eliminated unchanged in the urine

28
Q

How does decreased renal function influence half life of AG

A

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

29
Q

T/F: AG need to be supplemented after dialysis

A

TRUE

30
Q

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

A

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

31
Q

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

A

therapeutic concentration; increased mortality in these patients

32
Q

Standard dosing is determined by

A

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

33
Q

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

A

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

34
Q 
Gentamicin desired peak levels in (traditional dosing)
gram (-) 
Mild -
Moderate - 
Severe -

gram synergy (+) -

A

gram (-)
4-6
6-8
8-10

gram (+)
3-5

35
Q 
Gentamicin desired trough levels in (traditional dosing)
gram (-) 
Mild -
Moderate - 
Severe -

gram synergy (+) -

A

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

gram (+)
1

36
Q

dosing for once-daily dosing of AG

A

5-7 mg/kg/dose

37
Q

dosing for traditional dosing of AG

A

1-2.5 mg/kg/dose

38
Q

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

A

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

39
Q

In extended interval dosing subsequent dosing is based on?

A

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

40
Q

Desired peak and trough levels from extended interval dosing

A

peak: 13-20
trough: <0.5

**rarely obtained in once-daily/extended interval

41
Q

T/F: AG are rarely used alone

A

TRUE

42
Q

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

A

Amik, Gent, Tobra

43
Q

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

A

gent and strep

44
Q

Which two AG are used in the tx of tuberculosis

A

Amikacin and streptomycin

45
Q

Most common side effects

A

nephrotoxicity & Ototoxicty

46
Q

T/F: nephrotoxicity is irreversible if caused by AG

A

False: if caught early enough it is reversible

47
Q

What are the risk factors for nephrotoxicity

A

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

48
Q

T/F: Ototoxicity damage is irreversible

A

True- must be caught early to prevent detrimental loss

same risk factors as nephrotox

49
Q

what rare ADE is seen with neomycin

A

neuromuscular blockade

PHRM 865 EXAM2 (3 decks)

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