aminoglycosides

Question 1

MOA

Answer 1

Aminoglycosides irreversibly bind to the 30S ribosomal subunit (some to 50S subunits), which results in a disruption in the initiation of protein synthesis, a measurable decrease in protein synthesis, and misreading of messenger RNA

rapidly bactericidal in a concentration-dependent manner

Question 2

Mechanism of resistance

Answer 2

1.Alteration in aminoglycoside uptake
2.Synthesis of aminoglycoside-modifying enzymes
3.Alteration in ribosomal binding sites -rare

Question 3

Spectrum of activity

Answer 3

Gram-negative aerobes:
Acinetobacter spp. (not plazo)
Proteus spp.
Citrobacter spp.
Providencia spp.
E. coli
Pseudomonas aeruginosa**
Enterobacter spp.
Salmonella spp.
Klebsiella spp.
Serratia marcescens
Morganella morganii
Shigella spp.

Gram positive aerobes - never used alone always with cell wall active agents
Viridans streptococci
Enterococcus spp. (gentamicin or streptomycin)
Most strains of Staphylococcus aureus and coagulase-negative staphylococci

Mycobateria: Streptomycin is active against Mycobacterium tuberculosis

Question 4

Pharmacology

Answer 4

Highly polar cations
Must use IBW when dosing

Question 5

Absorption

Answer 5

Poor GI absorption
well absorbed after IM - peak concentration occurs 30 to 120 minutes after IM injection
IV infusion is preferred route of administration

Question 6

Distribution

Answer 6

distributed primarily in the extracellular fluid compartment
distribute poorly into CSF

Question 7

Elimination

Answer 7

Eliminated unchanged by the kidneys - decreases in renal function directly influence elimination causing prolonged half life

Question 8

Serum concentration monitoring

Answer 8

Because of interpatient variability in pharmacokinetic parameters and the narrow therapeutic index of the aminoglycosides, serum concentration monitoring is necessary in ALL patients.

must achieve therapeutic concentration within 24 hours as studied show increased mortality with sub-therapeutic levels

Question 9

Adverse Effects

Answer 9

1. Nephrotoxicity
2. Ototoxicity
   - risk factors: prolonged use >2 weeks, presence of renal insufficiency, advanced age, concomitant use with Vancomycin, Loop diuretics (ototox-), Cisplatin(nephro-)
3. Neuromuscular blockade

Question 10

Drugs in class

Answer 10

Gentamicin, Tobramycin, Amikacin, Streptomycin, and Plazomicin