Antibacterials-Aminoglycoside Antibiotics

Question 1

what is the general structure of Aminoglycoside Antibiotics

Answer 1

aminoglycoside antibiotics have 1,3-diaminocyclitol “core structures” that are usually linked to one or more aminoglycoside rings.

Question 2

clinically important aminoglycoside antibiotics

Answer 2

Tobramycin
Kanamycin A
Kanamycin A
Gentamicin C2
Neomycin B
Streptomycin
Spectinomycin

Question 3

how do Aminoglycoside Antibiotics work?

Answer 3

inhibit protein biosynthesis by binding to the 30S ribosomal subunit
-They bind to the 16S rRNA forming the A site. This interferes with formation of the initiation
complex, blocks further translation, and elicits premature termination

Question 4

what else do Aminoglycoside Antibiotics to ribosomal “proof reading”?

Answer 4

causes impairment of the proofreading function of the ribosome and formation of “nonsense proteins” resulting from selection of the wrong amino acids during translation

Question 5

what do these “non sense proteins” do to the bacterial cell wall?

Answer 5

“nonsense proteins” impair bacterial
cell wall function. The damaged membranes have altered permeability characteristics and actually allow transport of larger amount of aminoglycoside, and protein synthesis ceases altogether
-aminoglycosides lead to leakage of ions and disruption of the cytoplasmic membrane, resulting in cell death

Question 6

what are two ways Aminoglycosides can enter the cell?

Answer 6

1. initial entry of the positively charged aminoglycosides through the outer membrane involves the displacement of Mg++ and Ca++ ionsthat form salt bridges with phosphates of the phospholipids in the membrane. This makes the membrane more permeable to the aminoglycosides
2. Passage through the cytoplasmic membrane is an active transport process

Question 7

what are 3 ways resistance have formed againsted aminoglycosides?

Answer 7

1. metabolism
2. altered ribosomes
3. altered aminoglycoside uptake

Question 8

resistance: metabolism

Answer 8

Bacteria inactivate aminoglycosides by acetylation, adenylation, and phosphorylation.

Question 9

resistance: altered ribosome

Answer 9

The 16S rRNA binding site can be altered through point mutations. This has been observed clinically with Mycobacterium tuberculosis.

Question 10

resistance: altered aminoglycoside uptake

Answer 10

The rate of emergence is far less than resistance due to

metabolism, and the phenotype reverts after the drug is removed

Question 11

toxicity to aminoglycosides

Answer 11

All aminoglycosides are ototoxic (irreversible) and nephrotoxic (reversible)

Question 12

irreversible toxicity

Answer 12

The irreversible ototoxicity can result initially in tinnitus and high-frequency hearing loss, or in vestibular damage resulting in vertigo, loss of balance, and ataxia

Question 13

what should aminoglycosides not be taken with

Answer 13

loop diuretics

-increase risk for nephrotoxicity

Question 14

why shouldn’t aminoglycosides be take with loop diuretics?

Answer 14

Concurrent use with loop diuretics (ethacrynic acid and furosamide) or other nephrotoxic antimicrobial drugs (vancomycin or amphotericin) can potentiate nephrotoxicity and should be avoided
-Creatinine clearance can be monitored and the dose decreased in order to avoid nephrotoxicity

Question 15

when can toxicity present with aminoglycosides?

Answer 15

1. )5 days of treatment if elderly,
2. ) renal impairment,
3. ) higher doses
4. ) age

Question 16

what effect can aminoglycosides act like?

Answer 16

Curare-like effects are less common but can result from large doses of aminoglycosides.

• can cause respiratory distress
• Respiratory paralysis can usually be reversed by neostigmine or calcium gluconate, but mechanical respiratory assistance may be necessary.

Question 17

is aminoglycosides altered in urine?

Answer 17

no

Question 18

therapeutic use of aminoglycosides

Answer 18

Although the aminoglycosides have broad spectrum antibiotic activity against both Gram-(+) and
Gram-(-) bacteria, in practice their use is almost always reserved for treatment of Gram-(-) bacteria.

Question 19

what are aminoglycosides usually administered with?

Answer 19

penicillins

Question 20

how should aminoglycosides and penicillins be administered together?

Answer 20

• NOT together!, both drugs inactivated
• administered in different compartments (typically one in each arm) in order to avoid a chemical reaction between the two classes.

Question 21

what are aminoglycosides and penicillins used to treat?

Answer 21

bacterial endocarditis

Question 22

streptomycin is used for

Answer 22

TB

Question 23

spectinomycin is used for

Answer 23

gonorrhea

Question 24

gentamicin is used for?

Answer 24

urinary tract infections
burns
some pneumonias,
joint and bone infections caused by susceptible Gram-(-) infections

Question 25

most important antibiotic for therapeutic use for aminoglycosides?

Answer 25

gentamicin

Question 26

nephrotoxicity most likely to occur when?

Answer 26

• taking loop diuretics
• gentamicin
• can asses using creatinine clearance.