Pharmacology 14: Aminoglycosides

Question 1

Suffix for Streptomyces

Answer 1

-mycin (ie. Neomycin)

Question 2

Suffix for micromonospora

Answer 2

-micin (ie. Gentamicin)

Question 3

Streptomycin

Answer 3

Prototypic aminoglycoside, part of the Streptomyces classification
Oral

Question 4

Kanamycin

Answer 4

Topical or oral dosing

Streptomyces

Question 5

Amikacin

Answer 5

A derivative of kanamycin

Question 6

Neomycin

Answer 6

Mainly a topical drug but may be given orally

Question 7

Netilimicin

Answer 7

Broad Spectrum

Question 8

Why are Gentamycin, Tobramycin and Amikacin the most widely used drugs of the aminoglycoside class ?

Answer 8

Lower toxicity and broader spectrum of coverage

Question 9

Are aminoglycosides polar or non-polar ? What does this imply about their ability to cross the lipid membrane ?

Answer 9

They are highly polar and charged. This makes it difficult for them to pass the lipid membrane w/o some form of transport

This is accomplished by an energy-dependent active bacterial transport mechanism that requires oxygen and an active proton motive force.
– For this reason, aminoglycosides work poorly in anaerobic and acidic environments such as abscesses.

Question 10

MOA for Aminoglycosides

Answer 10

Inhibition of bacterial protein synthesis through irreversible binding to the 30S bacterial ribosome.

Question 11

Why do beta-lactams and vancomycin show additive effects when used in conjunction with aminoglycosides ?

Answer 11

Aminoglycosides must get past the cell wall to be effective. Drugs like beta-lactams and vanco inhibit cell wall synthesis making it easier for aminoglycosides to go about their business.

Question 12

Mechanism of Action at low doses of amino glycosides

Answer 12

misreading of mRNA during elogation leading to the incorporation of incorrect proteins into the bacterial proteins making them functionally useless

Question 13

Mechanism of action at high doses of aminoglycosides

Answer 13

complets inhibition of protein elongation causing the Ribosome-mRNA complex to be stopped at the start codon

Question 14

Where do aminoglycosides have significant toxicity within the body ?

Answer 14

Ears (Ototoxicity)

Kidneys (Nephrotoxicity)

Question 15

Against which class of bacteria are aminoglycosides often used ?

Answer 15

Enterobacteriaceae (Pseudomonas aeruginosa)

Question 16

Why might you use Tobramycin or Amikacin instead on Gentamycin ?

Answer 16

Gentamycin resistance has become prevalent in many care settings. The other two drugs are functionally similar but may be more effective in treating gentamycin resistant strains.

Question 17

What are the three ways in which aminoglycosides inhibit bacterial protein productions ?

Answer 17

1. Block initiation
2. Block elongation
3. Cause incorrect AA’s to be inserted in to the growing protein.

Question 18

What causes resistance due to lack of accumulation of AG’s in the bacterium ?

Answer 18

Most often the presence of efflux pumps

Question 19

What causes resistance due to modification of aminoglycosides to inactive molecules ?

Answer 19

Bacterial enzymes

Acetyltransferases
Nucleotidyltransferases
Phosphotransferase

Modification inhibits AG’s ability to bind the ribosome

Question 20

What causes resistance due to the inability of AG’s to bind ribosome w/o being previously modified by bacterial enzymes ?

Answer 20

Mutation of the bacterial ribosome so that recognition site for AG’s is no longe the same.