Amimoglycoside Antibiotics

Question 1

How do aminoglycosides inhibit protein biosynthesis?

Answer 1

by binding to the 30S ribosomal subunit - they bind to the 16S rRNA forming the A site

Question 2

What happens when aminoglycosides bind to the 16S rRNA (forming the A site)?

Answer 2

This interferes with formation of the initiation complex, blocks further translation, and elicits premature termination

Question 3

What happens when aminoglycosides impair the proofreading function of the ribosome?

Answer 3

formation of “nonsense proteins” resulting from selection of the wrong amino acids during translation

Question 4

What do “nonsense proteins” do to the bacteria?

Answer 4

impair bacterial cell wall function

Question 5

significance of damaged bacterial membranes?

Answer 5

damaged membranes have altered permeability characteristics and actually allow transport of larger amounts of aminoglycoside, and protein synthesis ceases altogether

Question 6

What do aminoglycosides ultimately lead to?

Answer 6

leakage of ions and disruption of the cytoplasmic membrane, resulting in cell death

Question 7

Describe the metabolism mechanism of aminoglycoside bacterial resistance.

Answer 7

bacteria inactivate aminoglycosides by acetylation, adenylation, and phosphorylation

Question 8

Resistance can emerge to aminoglycosides in general because many of the metabolizing enzymes have?

Answer 8

cross-resistance specificity

Question 9

Describe the mechanism of aminoglycoside resistance where the ribosomes are altered.

Answer 9

The 16S rRNA binding site can be altered through point mutations

Question 10

Toxicity of aminoglycosides.

Answer 10

ototoxic (irreversible) and nephrotoxic (reversible)

Question 11

What are the symptoms of aminoglycoside ototoxicity?

Answer 11

irreversible tinnitus and high-frequency hearing loss, or in vestibular damage resulting in vertigo, loss of balance and ataxia

Question 12

What should you do in high risk patients if you are concerned about ototoxicity?

Answer 12

obtain a serial audiogram for early recognition

Question 13

Risk factors for ototoxicity with aminoglycosides?

Answer 13

concurrent use of other ototoxic drugs (loop diuretics or vancomycin), compromised renal function or genetic vulnerability

Question 14

loop diuretics

Answer 14

ethacrynic acid and furosamide

Question 15

What can potentiate nephrotoxicity with aminoglycosides?

Answer 15

concurrent use with loop diuretics (ethacrynic acid and furosamide) or other nephrotoxic antimicrobial drugs (vancomycin or amphotericin)

Question 16

What should be monitored in order to avoid nephrotoxicity?

Answer 16

creatinine clearance (changes in GFR)

Question 17

Evidence of ototoxicity or nephrotoxicity with aminoglycosides requires you to?

Answer 17

discontinue the drug or adjust the dose

Question 18

What type of effects can result from large doses of aminoglycosides?

Answer 18

curare-like effects (less common)

Question 19

How can the respiratory paralysis (curare-like effects) from aminoglycoside toxicity be reversed?

Answer 19

by neostigmine or calcium gluconate (mechanical respiratory assistance may be necessary)

Question 20

The likelihood of aminoglycoside toxicity increases if?

Answer 20

the treatment period is longer than 5 days, in the elderly if renal function is impaired and in higher doses

Question 21

Since more effective and less toxic alternatives to aminoglycosides are available, they should be used…?

Answer 21

sparingly and only for specific indications

Question 22

In practice, aminoglycosides are almost always reserved for treatment of?

Answer 22

gram (-) bacteria

Question 23

Aminoglycosides are often used in combination with?

Answer 23

penicillins - synergism between the two classes of antibiotics

Question 24

How should a combination of an aminoglycoside and a penicillin be administered?

Answer 24

should be administered in different compartments in order to avoid a chemical reaction between the two classes (penicillins and aminoglycosides attack and destroy each other)

Question 25

What should you not do with aminoglycosides and penicillin?

Answer 25

do not mix them together in the same solution

Question 26

penicillin/aminoglycoside combinations are used to treat?

Answer 26

bacterial endocarditis

Question 27

Streptomycin is most often used to treat?

Answer 27

tuberculosis

Question 28

Most important of the aminoglycosides

Answer 28

gentamicin

Question 29

Gentamicin is used to treat?

Answer 29

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

Question 30

Which aminoglycoside has retained antibacterial activity against aminoglycoside-resistant strains (still used to treat nosocomial infections)?

Answer 30

amikacin