Aminoglycosides

Question 1

Aminoglycosides

Answer 1

First group of antibiotics that are dosed individually for each patient and require serum concentration monitoring.
Ex.
Gentamicin
Tobramycin
Amikacin
Streptomycin

Question 2

Aminoglycosides Mech of Action

Answer 2

IRREVERSIBLY bind to 30S ribosomal subunit (and some 50S), thus disrupting protein synthesis.
Require aerobic energy to enter cell & bind ribosomes.

Question 3

Aminoglycosides- Bactericidal or Bacteriostatic?

Answer 3

RAPIDLY CONCENTRATION-DEPENDENT BACTERICIDAL; need to assure adequate levels

Has PAE

Question 4

Mechanisms of Resistance to Aminoglycosides

Answer 4

Alteration in aminoglycoside uptake (chromosomal mutation)
Synthesis of aminoglycoside-modifying enzymes (plasmid-mediated)
Alteration in ribosomal binding sites

Question 5

Aminoglycosides Spectrum of Activity

Answer 5

Gram (-) Aerobes incl. PSEUDOMONAS AERUGINOSA
Mycobacteria
NOT ACTIVE against anaerobes
NOT ACTIVE against Gram (+) aerobes unless given with cell-wall agent (primarily gentamicin)

Question 6

Aminoglycosides Synergy

Answer 6

Exhibit synergy when combined w/ cell-wall active agents like B-lactams and vancomycin

Question 7

Aminoglycosides Absorption

Answer 7

Poorly absorbed from G.I. tract
IV infusion is preferred route of administration
IM injection rarely used, except streptomycin

Question 8

Aminoglycosides Elimination

Answer 8

85-95% is ELIMINATED UNCHANGED BY THE KIDNEY

= HIGH URINARY CONCENTRATIONS

Question 9

Aminoglycosides Clinical Uses Overview

Answer 9

RARELY USED AS MONOTHERAPY
Largely replace by B-Lactams
UTIs
septsis, esp. from urinary tract
intraabdominal infections
skin and soft tissue infections
does not penetrate into lung, so cannot be used alone for pneuomonia

Question 10

Amikacin Clinical Uses

Answer 10

Gram (-) infections w/ multi-drug resistance
Least likely to be inactivated by bacterial resistance enzymes
Less renal toxicity

Question 11

Gentamicin & Streptomycin Uses

Answer 11

Used for synergy w/ cell wall active antibiotics
Used in combination w/ B-lactams or vancomycin to treat endocarditis caused by Staphylococcus spp., viridans strep, Enterococcus spp.

Question 12

Streptomycin Clinical Uses

Answer 12

Injectable drug for the treatment of M. tuberculosis

Question 13

Aminoglycosides Adverse Effects

Answer 13

NEPHROTOXICITY
- risk factors include PROLONGED HIGH TROUGH CONCENTRATIONS

OTOTOXICITY- AUDITORY AND VESTIBULAR
IRREVERSIBLE

Neuromuscular blockage, cannot be used in patients w/ myasthenia gravis