Aminoglycosides

Question 1

Aminoglycosides - Name the 6

Answer 1

1. Gentamicin
2. Neomycin
3. Streptomycin
4. Tobramycin
5. Amikacin
6. Netilmicin

Question 2

Aminoglycosides - MOA (3 effects)

Answer 2

Antimicrobial; bactericidal

Effects of aminoglycosides on protein synthesis.

1. Binds to the 30S ribosomal subunit and interferes with initiation of protein synthesis by fixing the 30S-50S ribosomal complex at the start codon (AUG) of mRNA
2. Binding to the 30S subunit also causes misreading of mRNA, leading to A). premature termination of translation with detachment of the ribosomal complex and incompletely synthesized protein or B). incorporation of incorrect amino acids, resulting in the production of abnormal or nonfunctional proteins.

Question 3

Aminoglycosides - Tx (2)

Answer 3

Complicated pyelonephritis and catheter associated UTI (given IV) in combo w/ a fluoroquinolone, 3rd gen cephalosporin, or piperacillin-tazobactam

Question 4

Aminoglycosides - MOR (3 enzymes)

Answer 4

Resistance via plasmid mediated enzymes that inactivate the drug –> acetylase, adenylase, phosphorylase

Question 5

Aminoglycosides - Tox (4)

Answer 5

1. Ototoxicity (irreversible damage to vestibular and cochlear sensory cells)
2. Neuromuscular blockade (inhibits ACh release from preganglionic terminal via competition w/ Ca2+ –> antagonized by Ca2+ salts and anti-AChE)
3. Nephrotoxicity (mild reversible impairment (decreased concentrating, mild proteinuria, casts) –> acute tubular necrosis –> due to accumulation of and retention of drug in PCT cells) => may prevent drug excretion and increase ototoxicity
4. Teratogenic

Question 6

Gentamicin ; Tobramycin; Amikacin; Netilmicin; Streptomycin; Neomycin - Class

Answer 6

Aminoglycosides

Question 7

How do you give Gentamicin?

Answer 7

IV or IM (protected from 1 type of acetylase enzyme)

Question 8

How do you give Tobramycin and what is it best w/?

Answer 8

IV, IM, or inhalation

Superior activity against P. aeruginosa in combo w/ pseudomonal beta-lactamase inhibitor

Not protected from any of the 3 MOR enzymes

Question 9

How do you give Amikacin and what is it best w/?

Answer 9

IV or IM

Broad spectrum against gram (-) bacteria
Lowest resistance rates (because only acetylase can inactivate it at 1 site)

Question 10

Netilmicin - good for

Answer 10

Broad spectrum against gram (-) bacteria

Protected against 1 type of acetylase enzyme and adenylase at 1 site

Question 11

Streptomycin - major toxicity?

Answer 11

Higher ototoxicity

Question 12

Neomycin - used for and major tox?

Answer 12

Oral, topical, and bladder irrigation

Hypersensitivity toxicity

Question 13

What usually causes a urinary catheter associated UTI?

Answer 13

Enterobacteriaceae (gram negative bacilli)

Question 14

What are the 2 major SE of Aminoglycosides?

Answer 14

Nephrotoxicity and ototoxicity

Question 15

Why does ototoxicity develop?

Answer 15

Results from progressive damage to vestibular and cochlear sensory cells, which is usually irreversible

Question 16

Toxicities associated with aminoglycosides are _____-dependent

Answer 16

dose

Question 17

Why do aminoglycosides produce neuromuscular blockade?

Answer 17

By inhibiting acetylcholine release from the preganglionic terminal (through competition with Ca2+) and to a lesser extent by noncompetitively blocking the receptor.

Question 18

How can you antagonize the neuromuscular blockade caused by aminoglycosides?

Answer 18

Ca2+ salts but only inconsistently by anti-cholinesterase agents

Question 19

What is the other class of antibiotics that can cause neuromuscular blockade?

Answer 19

Tetracyclines (thought to be through chelation of Ca2+)

Question 20

How many pts who receive aminoglycoside develop renal toxicity?

Answer 20

Up to 26% of patients (who receive an aminoglycoside for more than several days) will develop mild, reversible renal impairment.

Question 21

How does renal toxicity develop from aminoglycosides?

Answer 21

From accumulation and retention of aminoglycoside in the proximal tubular cells.

Question 22

How does renal toxicity from aminoglycosides present initially? (3)

Answer 22

Defect in renal concentrating ability, mild proteinuria, and the appearance of hyaline and granular casts.

Question 23

With prolonged use of aminoglycosides how does the renal toxicity change? (2)

Answer 23

1. The GFR is reduced after several additional days. 2. The nonoliguric phase of renal insufficiency is thought to be due to the effects of aminoglycosides on the distal portion of the nephron with a reduced sensitivity of the collecting-duct epithelium to endogenous antidiuretic hormone.

Question 24

Does acute tubular necrosis (ATN) happen with aminoglycosides’ usage?

Answer 24

Severe ATN may occur rarely, but the most common significant finding is a mild rise in plasma creatinine.

Question 25

Is renal function impairment from aminoglycoside reversible?

Answer 25

Almost always b/c the proximal tubular cells have the capacity to regenerate.

Question 26

How does renal toxicity correlative with aminoglycoside usage?

Answer 26

Toxicity correlates with the total amount of drug administered. SO ATN is more likely to be encountered with longer courses of therapy.

Question 27

What is the most important result of renal toxicity from aminoglycosides?

Answer 27

Reduced excretion of the drug, which, in turn, predisposes to ototoxicity.