Pharm: Aminoglycosides

Question 1

Describe the “postantibiotic effect” and what this means for appropriate dosing of aminoglycosides.

Answer 1

The antibacterial effects of this class persist even after measurable levels of the drug cease. For this reason, they work much better when administered in ONE large dose instead of multiple small ones.

Question 2

Describe how measuring aminoglycoside concentration 8 hours after dosing allows estimates of clearance at 18 hours after and give the appropriate range.

Answer 2

The goal is to administer the drug so that its concentration reaches 1 microgram/mL by 18-24 hrs. This allows a “wash out” period so that the body is clear and ready for the next dose. This level can be estimated by measuring at 8 hrs. The range at 8 hrs. should be:

1.5 - 6 microgram/mL

Question 3

Describe the active transport of aminoglycosides into cells and why this limits their effectiveness under anaerobic conditions.

Answer 3

These drugs use an bacterial transport protein in the membrane that is energy dependent. The energy to run this pump is not produced without oxygen.
(aminoglycosides do not work well in abscesses which are anaerobic and acidic)

Question 4

Describe why administration of beta-lactams or vancomycin can enhance effectiveness of aminoglycosides.

Answer 4

The cell wall in bacteria can block access of aminoglycosides to the cell membrane where the transport protein is located that they use to enter the cell. Beta-lactams inhibit cell wall synthesis.

Question 5

What are the three types of drug effect on protein synthesis with explanations of the effect of each.

Answer 5

1. Drug blocks the formation of the initiation complex. 30S doesn’t bind 50S.
2. Miscoded Peptide Chain. Function of the translation complex is altered leading to faulty protein production.
3. Drug can bind the 30S unit and prevent movement down the mRNA (translocation) preventing protein formation.

Question 6

Give three general mechanisms of resistance to aminoglycosides and which is rarest.

Answer 6

1. Efflux pump: P glycoprotein pump actively removes antibiotic from the bacterial cell
2. Enzymes: bacteria can develop enzymes that lyse antibiotics within the cell
3. Mutation: very RARE, the bacterial 30S ribosome is mutated and the antibiotic doesn’t recognize it to bind and inhibit it

Question 7

Which class of microbes are aminoglycosides most indicated?

Answer 7

Aerobic Gram (-) bacilli

Question 8

Name four general disease conditions caused by the aerobic gram (-) bacilli that aminoglycosides are used to treat.

Answer 8

1. Bacteremia
2. Sepsis
3. Endocarditis (and prophylaxis to prevent IE)
4. After Urinary and Biliary Surgery

Question 9

Why did amikacin replace gentamicin?

Answer 9

Resistance developed for gentamicin and amikacin also has a more broad spectrum.

Question 10

3 medications to use against Pseudomonas.

Answer 10

Tobramycin, amikacin, gentamicin

Question 11

Why can’t aminoglycosides pass thru the bacterial cell membrane to be effective?

Answer 11

They are polar (positive charged) and are repelled by the lipophilic membrane.

Question 12

What are the main adverse effects of aminoglycosides?

Answer 12

They can accumulate in the CSF, vitreous humor, brain, prostate,and renal cortex.

• cochlear and vestibular toxicity
• renal toxicity
• neuromuscular disorders