Exam 8: Aminoglycosides

Question 1

Name 4 Aminoglycosides

Which is used least commonly?

Answer 1

Gentamicin
Tobramycin
Amikacin
Streptomycin (least commonly used)

Question 2

When would you administer an aminoglycoside orally? Why?

Answer 2

GI indication

It is very poorly absorbed through he GI tract

Question 3

How are aminoglycosides usually administered?

Answer 3

IV (mostly) or IM

Question 4

How often are aminoglycosides usually administered? Which is now preferred?

Answer 4

2-3x per day
New, once daily regimens may be preferred
** He mentioned multiple times that the 2-3x/day regimen is more likely to cause toxicity

Question 5

Why is once-daily admin advantageous with aminoglycosides?

Answer 5

Super high plasma concentrations kill more bugs (dose-dependent killing)
Less TIME with concentrations above the “Toxic Trough” (less likely to cause adverse effects)

Question 6

How do aminoglycosides distribute in the body?

Answer 6

Not very well (polar compounds)
Dont enter CNS
Can be administered intrathecally (better options though usually like 3rd gen cephalosporins)

Question 7

How do aminoglycosides enter bacterial cells?

Answer 7

Diffuse through porin channels in the outer membrane in gram negatives
Cross plasma membrane via an oxygen-dependent active transport process (not good with anaerobic infections!)

Question 8

What can enhance transport of aminoglycosides into bacterial cells?

Answer 8

Antibiotics that inhibit bacterial cell wall synthesis (beta lactams)

Question 9

What antibiotics have a synergistic killing effect with aminoglycosides?

Answer 9

Beta lactams

They allow more aminoglycoside penetration into bacterial cells.

Question 10

Where do high concentrations of aminoglycosides accumulate?

Answer 10

Renal cortex
Inner Ear
This is why they can cause nephrotoxicity and ototoxicity

Question 11

How are aminoglycosides eliminated?

Answer 11

By the kidneys

Adjust dose in renal failure, otherwise you’ll get really high concentrations/toxicity

Question 12

What are 3 mechanisms of aminoglycosides?

Answer 12

1. Irreversible binding to the 30S ribosomal subunit inhibits bacterial protein synthesis (translation)
2. Causes breakup of 70S subunit into 30S and 50S
3. Cause misreading of mRNA leading to mutated proteins (this accounts for killing effect even at concentrations below M.I.C.)

Question 13

What stage of protein synthesis do aminoglycosides inhibit?

Answer 13

Initiation

Question 14

What are 3 adverse effects associated with aminoglycosides?

Answer 14

1. Ototoxicity
2. Nephrotoxicity
3. Neuromuscular block (Curare like effect)

Question 15

How do aminoglycosides cause ototoxicity?

Answer 15

Accumulation in perilymph and endolymph of inner ear

Causes irreversible destruction of vestibular and cochlear sensory cells

Question 16

What increases the risk of aminoglycoside causes ototoxicity? (3 things)

Answer 16

1. Co-administration of ethacrynic acid, vancomycin, or cisplatin
2. Renal failure
3. High doses

Question 17

What are two manifestations of ototoxicity?

Answer 17

Auditory problems

Vestibular problems

Question 18

What kind of nephrotoxicity is caused by aminoglycosides?

Answer 18

Acute Tubular Necrosis in the proximal tubule

Monitor creatinine

Question 19

What is different between the ototoxicity and the nephrotoxicity caused by aminoglycosides?

Answer 19

The nephrotoxicity may be reversible

The ototoxicity is irreversible

Question 20

How can aminoglycosides cause neuromuscular block? (2 ways)

Answer 20

Inhibit ACh release

Inhibit postsynaptic sensitivity to ACh

Question 21

How do you treat aminoglycoside induced NM blockade?

Answer 21

IV Calcium and an Acetylcholinesterase inhibitor

Question 22

How can you treat the patient if you end up with toxic levels of aminoglycosides?

Answer 22

Hemodialysis

Question 23

What should you be doing if you have a patient on aminoglycosides?

Answer 23

Monitoring blood levels

Make sure that you’re achieving therapeutic levels and that you’re not having concentrations too high.

Question 24

What is an important resistance mechanism to aminoglycosides?

Answer 24

Production of bacterial enzymes that phosphorylate, adenylate, or acetylate the aminoglycoside so it can’t bind to the 30S subunit.
Genes are usually on plasmids, which often contain other resistance genes

Question 25

What is the most resistant aminoglycoside to inactivating enzymes?

Answer 25

Amikacin

Question 26

What is a resistance mechanism specific to streptomycin?

Answer 26

Mutated 30S subunit

Question 27

How could you use aminoglycosides to treat Enterococci?

Answer 27

Gentamicin or streptomycin PLUS a beta lactam

Question 28

What are aminoglycosides really good at treating?

Answer 28

Aerobic gram negatives

Proteus, E. coli, Klebsiella

Question 29

What are the major uses of Aminoglycosides?

Answer 29

Severe systemic infections caused by gram negatives

In combo with beta lactams to treat endocarditis

Question 30

Streptomycin

Answer 30

Used in combo with Penicillin G to treat bacterial endocarditis
Can treat gentamicin-resistant enterococci
TB

Question 31

Gentamicin Uses

Answer 31

Hospital acquired UTI (gram neg)
Hospital acquired pneumonia in combo with an antipseudomonal (gram neg rods)
NOT good at CAP (Strep. pneumo.)
Enterococcal endocarditis (with penicillin G)
Sepsis caused by gram negatives

Question 32

Tobramycin Uses

Answer 32

Better activity against Pseudomonas (sepsis, osteomyelitis, pneumonia)
Can be inhaled in patients with CF and pseudomonas infections

Question 33

Amikacin

Answer 33

Broadest spectrum aminoglycoside
Resistant to inactivating enzymes
reserved for serious infections caused by gram negatives that don’t respond to the aminoglycosides