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Pharm test #3 > Aminoglycosides > Flashcards

Aminoglycosides Flashcards

1
Q

what are the common aminoglycosides

A

Gentamicin
Tobramycin
amikacin
streptomycin

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2
Q

how do aminoglycosides work

A

Irreversibly bind to 30S ribosomal subunit of susceptible bacteria resulting in inhibition of protein synthesis
Cell entry is oxygen-dependent

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3
Q

mechanisms of resistance to aminoglycosides

A

• Synthesis of AG modifying enzymes
Plasmid-mediated
>50 AG altering enzymes
Cause acetyl-, adenyl-, or phosphorylation
these changes usually result in altered uptake or binding
• Altered AG uptake
Loss of porin channel
Efflux pump
• Change in ribosomal binding site/target modification

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4
Q

gentamicin spectrum of activity

A 
Gram-negative
E. coli
K. pneumoniae
Proteus
Citrobacter
Enterobacter
Morganella
Serratia
Pseudomonas
Gram-positive
Enterococcus
S. aureus
Viridans Streptococcus
S. pyogenes

very good gram negative, has the best synergy for enterococcus treatment

least pseudomonas activity of the aminoglycosides

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5
Q

what would you use to treat enterococcus (gram +)

A

gentamicin + ampicillin (or another pcn or vancomycin)

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6
Q

Spectrum of Activity 
Tobramycin

A

Gram-negative

Similar to gentamicin BUT
More active against Pseudomonas**

Slightly less active against other gram-negatives

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7
Q

Spectrum of Activity
 Amikacin

A

Gram-negative
Generally, most active against nosocomial gram-negatives (except vs tobra for Pseudomonas, most of the time)

Mycobacterial
M. tuberculosis
Atypical mycobacteria

Others
Nocardia

used as a broad spectrum 2nd choice empiric therapy

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8
Q

what to use when treating Pseudomonas with an aminoglycoside

A

Tobramycin

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9
Q

Spectrum of Activity 
Streptomycin

A

Gram-positive
Enterococcus

Mycobacterial
M. tuberculosis
Less atypical mycobacteria than amikacin

mainly used for Enterococcus if gentamicin cannot be used

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10
Q

aminoglycosides and synergy

A
  • Synergy between cell wall active agents and AGs

* Likely due to enhanced AG uptake

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11
Q

aminoglycoside distribution

A
  • Low in CSF, bronchial secretions, bile (30%), vitreous humor (40%)
  • high/good Pleural, pericardial, ascitic, and synovial fluid ~50% of serum
  • High in urine
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12
Q

aminoglycoside elimination

A

99% renally eliminated (urine conc ~ 50-100x serum conc)
30-40% removed by hemodialysis
Linear PK - doubling the dose doubles the concentration

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13
Q

Pharmacodynamics

A
  • Concentration-dependent killing

* PK/PD parameter: peak/MIC (goal ≥ 8 – 10) higher = more optimal efficacy

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14
Q

Postantibiotic Effect

A

Persistent suppression of bacterial growth after drug concentration falls below the MIC of targeted organism

wide range of aminoglycosides

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15
Q

Postantibiotic Effect is impacted by

A

Organism
Drug concentration
Duration of drug exposure
Antimicrobial combinations

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16
Q

Dosing 
Gentamicin and Tobramycin for a gram negative infection

A

Traditional : doses give 3x a day or every 8 hours - keeps a more constant low level of drug present

extended interval (once a day) dosing : give one large dose per day - higher peak lower trough

17
Q

Dosing 
Amikacin for gram negative

A

doses are 2-3x what you would give for gentamicin or tobramycin.

may use traditional or extended interval

18
Q

Dosing
 for Gram-positive infections

A

use either gentamicin or streptomycin, gram positive bacteria are killed time dependently therefore multiple smaller and more frequent doses are given

19
Q

Dosing 
Mycobacterial infections

A

Amikacin/streptomycin given in high doses (higher than for gram negative) once a day or less but over a much longer time period (months)

20
Q

Traditional vs. Extended-Interval Dosing

A 
Traditional dosing (MDD)
Approximately same daily dose given every 8 to 12 hours

Extended-interval dosing (ODA)
One large dose given at an interval no less than every 24 hours

21
Q

Rationale for Extended-Interval Dosing

A 
Concentration-dependent bactericidal activity
Post-antibiotic effect (PAE)
Adaptive resistance - may become less resistant during off time
Minimize toxicities
Nephrotoxicity
Ototoxicity
Cost savings
Efficacy
22
Q

Nephrotoxicity of aminoglycoids

A
  • Related to intracellular accumulation of drug in the renal cortex
  • Uptake of AGs into proximal tubule cells is saturable at clinically achieved concentrations
  • Animal studies have shown that continuous infusion AG results in higher renal cortical concentrations compared with a single daily injection regimen – thought to be due to the amount accumulated over time not peak concentration
  • REVERSIBLE
23
Q

ways to decrease nephrotoxicity

A

give higher doses less frequently

make sure to get a low trough level to give kidney time without drug

24
Q

Ototoxicity with aminoglycoids

A
  • Uptake of AGs into different inner ear tissues does not correlate with the degree of ototoxicity
  • Sparse data for risk of ototoxicity based on dosing regimen
  • does not seem to correlate with any dosing perimeter
25
Q

how does extended interval dosing save money

A

Decreased pharmacy preparation time

Decreased nursing administration time

Potentially decreased drug concentration monitoring

26
Q

Clinical Uses of aminoglycoids for gram negative infections

A
  • gent, tobra, amikacin
  • In combination with beta-lactams to treat resistant and/or serious infections
  • Empiric treatment of sepsis, especially from a urinary source
  • Bloodstream, intraabdominal infections, skin/soft tissue infections
  • Need to use high dose if giving for pneumonia
  • Rarely used as monotherapy
27
Q

clinical uses of aminoglycoids for gram positive infections

A
  • mostly gent, some strepto
  • In combination with beta-lactams (ampicillin or nafcillin) or vancomycin for severe infections (enterococcal or staphylococcal endocarditis)
  • High peak concentrations are NOT necessary so low dose is sufficient
28
Q

aminoglycoid use for mycobacteria infections

A
  • amikacin, streptomycin

* In combination with multiple antimycobacterial agents

29
Q

risk factors for nephrotoxicities

A

prolonged/repeditive use, *elevated trough concentrations, prolonged therapy, underlying renal insufficiency, advanced age, hypovolemia, concomitant nephrotoxins

Gent > tobra > amik > strepto

30
Q

Ototoxicity risk factors

A

Usually irreversible (may appear after the end of treatment)

Risk factors: increased age, prolonged AG course, ?increased serum concentrations, ?genetic factors – not as well understood

31
Q

best way to enhance efficacy and minimize toxicity

A

get in and get out

optimize the Peak/MIC ratio by giving high but infrequent doses

Pharm test #3 (17 decks)

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