Dr. Roane Aminoglycosides Exam 2

Question 1

Name Aminoglycosides

Answer 1

Amikacin
Gentamicin
Neomycin
Neptilmicin
Streptomycin
Tobramycin

Question 2

What is the target site of Aminoglycosides?

Answer 2

30S subunit of bacterial ribosomes

Question 3

Mechanism of action of Aminoglycosides

Answer 3

1. Block initiation
2. Initiates premature termination
3. Incorporates incorrect amino acids

Question 4

What is the killing profile of Aminoglycosides?

Answer 4

-considered bacteriocidal (argueable)
-concentration-dependent killing
-post-antibiotic effect -> due to irreversible binding to ribosomes -> prolonged effect

Question 5

Spectrum of activity - Aminoglycosides

Answer 5

gram (+) cocci: Enterococcus (Aminoglycosides require synergistic treatment w/ 2 drugs and different MOA), Strep agalactiae

gram (-) rods: Klebsiella, Pseudomonas

Question 6

Why does Aminoglycoside often require a 2nd drug for treatment?

Answer 6

Because it bearly penetrates the cell wall -> a drug that disrupts the cell (f.e. ß-lactams) wall is needed

Question 7

What would be an example of synergy using Aminoglycosides for treatment?

Answer 7

Gentamicin + Streptomycin + VNC or Pen G for Enterococci

Question 8

How do Aminoglycosides enter bacterial cells?

Answer 8

By oxygen-dependent pumps
-> not effective against anaerobes

Question 9

What are the toxicities associated with Aminoglycosides?

Answer 9

-Ototoxicity: permanent tinnitus, vestibular actions (dizziness, imbalance)

-Nephrotoxicity
-Neuromuscular paralysis -> ACh effects at the NMJ (less common)

Question 10

How are Aminoglycosides eliminated from the body?

Answer 10

Renal Elimination -> Kidney
The half-life depends on the kidney function measured with Creatine clearance (CrCl) or creatine levels
-> Renal adjustment needed

Question 11

What causes Aminoglycoside toxicities?

Answer 11

Prolonged high plasma level
-Ototoxicity, Nephrotoxicity, Neuromuscular paralysis

Question 12

What is the dosing strategy for Aminoglycosides?

Answer 12

-One high dose/ 24h due to post-antibiotic effect

-High loading dose and lower maintenance dose

But there are considerations: pregnancy, Dialysis - renal function, fluid accumulation

Question 13

What is the most common form of resistance for Aminoglycosides?

Answer 13

Conjugation reactions: adding compounds to the Aminoglycosides such as -> Acetylation (by Acetylase) or Phosphorylation (Phosphorylase), Adenylation

Question 14

How is resistance to Aminoglycosides transmitted?

Answer 14

Through plasmids or chromosomal mutations,

-Resistance can also occur due to mutations on the ribosomal subunit -> drug doesn’t bind anymore

Question 15

Mechanism of Resistance

Answer 15

-mutations on the ribosomal subunit -> drug doesn’t bind anymore
-lack of permeability
-failure of active transport through the cell membrane
-ribosome methylation
-Efflux pumps

Question 16

What is Plazomicin (Zemdri) used for?

Answer 16

complicated UTI (cUTI)

-covers ESBL-producing Enterobacteriaceae
Carbapenem-resistant Enterobacteriaceae (CRE), and organisms with aminoglycoside-modifying enzymes

-Side effects are similar to those of other aminoglycosides
-drug of reserve

Question 17

Pharmacokinetics of Aminoglycosides

Answer 17

Absorption: not well absorbed orally due to sugar-like molecule -> often used an IV, IM, or ointment

Distribution: well throughout the body except brain, CSF, eye, prostate, bile

Excretion: half-life is 2-3 hours (normal kidney function), excreted by the glomerular function

Renal adjustment needed to avoid toxicity