Aminoglycosides

Question 1

What are the aminoglycosides?

Answer 1

Neomycin, Kanamycin/Amikacin, Gentamicin

Question 2

Are the aminoglycosides hydrophilic or hydrophobic?

Answer 2

Highly hydrophilic, lipid insoluble

Question 3

How well are aminoglycosides absorbed from the gut?

Answer 3

Not well. 3 - 5%

Question 4

Do aminoglycosides bind to plasma protein?

Answer 4

Not well. But bind readily to cellular debris

Question 5

How do aminoglycosides work?

Answer 5

Protein synthesis inhibition

Question 6

At what pH do aminoglycosides work best?

Answer 6

7.5 - 8.0

Question 7

Are aminoglycosides (protein synthesis inhibitor) bactericidal or -static?

Answer 7

Unique! Protein synthesis inhibitor that is bactericidal (most are bacteriostatic)

Question 8

Why do aminoglycosides not penetrate bacteria well?

Answer 8

Hydrophilic nature

Question 9

What are the 2 things that bacteria penetration relies on?

Answer 9

Energy dependent phase 1 (oxygen dependent)

Energy dependent phase II (disruption of cytoplasmic membrane)

Question 10

What can block energy dependent phase 1 of aminoglycosides?

Answer 10

Hyperosmolarity, low pH, anaerobic conditions

Question 11

Why are aminoglycosides bactericidal?

Answer 11

Energy dependent phase II disrupts cytoplasmic membrane and causes ion leakage

Question 12

What is the spectrum of aminoglycosides?

Answer 12

NO ANAEROBES.
++ Gram(+) Aerobes
+++++ Gram(-) Aerobes

Question 13

Which gram+ bacteria are aminoglycosides used for? Is there resistance?

Answer 13

Mostly staph. Some Streptococcus sp but many resistant

Question 14

Which gram- bacteria are aminoglycosides used for?

Answer 14

Enteric bacteria (Klebsiella, proteus shigella), Mannheimia, Pasteurella, Pseudomonas

Question 15

Why are aminoglcyosides not useful against gram- anaerobic?

Answer 15

Oxygen depedent, energy depdent phase I

Question 16

Why is Amikacin often used instead og Gentamicin/Tobramycin for enteric bacterial infections?

Answer 16

Resistant to enzymes produced by enterobacteriaceae

Question 17

Which aminoglycoside has the broadest spectrum?

Answer 17

Amikacin

Question 18

What is the most important aspect about plasmid-associated resistance genes?

Answer 18

Plasmid may carry resistance genes for multiple drug resistances (3+)

Question 19

What route can aminoglycosides be given?

Answer 19

IV, IM, SC

Question 20

Can you give aminoglycosides orally? If so, when?

Answer 20

Only when activity is targeted for GI tract

Question 21

Why are aminoglycosides poorly absorbed from GI tract?

Answer 21

Poorly lipid soluble

Question 22

Do aminoglycosides have a high or low Vd?

Answer 22

Very low because of hydrophilic nature

Question 23

Can aminoglycosides penetrate the CNS?

Answer 23

Not really

Question 24

Why are aminoglycosides more widely distributed in neonates?

Answer 24

High amount of extracellular fluid

Question 25

Where in the body do aminoglycosides concentrate most (highest tissue concentration)?

Answer 25

Renal cortex & cochlear tissue

Question 26

Why do aminoglycosides concentrate in the renal cortex & cochlear tissue?

Answer 26

High amount of phospholipids & anionic nature cellular matrix of these tissues

Question 27

What are the elimination half times of aminoglycosides?

Answer 27

Short, 1 - 3 hours

Question 28

What is the primary route of excretion for aminoglycosides?

Answer 28

Kidneys via parent compound

Question 29

What is the relationship between urine & serum concentrations for aminoglycosides?

Answer 29

Urine 100:1 serum

Question 30

What is the issue with intramammary administration of aminoglycosides in cattle?

Answer 30

Can diffuse back to plasma & prolong residues

Question 31

What is the target therapy serum concentration for aminoglycosides compared to MIC?

Answer 31

8 - 10x MIC of target pathogen

Question 32

How often is the peak for aminoglycoside concentration achieved during dosing?

Answer 32

Once a day

Question 33

Why are aminoglycosides dosed only once a day?

Answer 33

Dosing a bolus once a day increases the peak & allows a low trough prior to the next dose. This allows the renal and otic tissue concentrations to decline & decreases toxicity compared to frequent dosing

Question 34

Should you administer aminoglycosides by a constant IV infusion?

Answer 34

No!

Question 35

Which aminoglycoside is the most nephrotoxic?

Answer 35

Neomycin

Question 36

Can you use neomycin for systemic use?

Answer 36

NO. Nephrotoxicity

Question 37

List aminoglycosides in order of nephrotoxicity (least to most)

Answer 37

Amikacin < Gentamicin < Neomycin

Question 38

What other drug is contraindicated for concurrent use in aminoglycosides? Why?

Answer 38

Diuretics. They increase nephrotoxic potential.

Question 39

Why is it critical to allow aminoglycosides to reach a trough after peak concentration?

Answer 39

Decrease nephrotoxicity

Question 40

Considering nephrotoxicity data of aminoglycosides, describe the curve model (shape, meaning)

Answer 40

Bimodal. First phase is nonazotemic followed by azotemic

Question 41

Will cessation of aminoglycosides stop azotemia from progressing?

Answer 41

No

Question 42

Which species is most susceptible to the ototoxic effects of aminoglycosides? Do they experience vestibular effects or auditory effects? What is the other common species that experiences ototoxic effects?

Answer 42

Cats, vestibular | Dogs experience auditory

Question 43

Will renal toxicity or ototoxicity occur first?

Answer 43

Renal before substantial ototoxicity

Question 44

What is the concern when using aminoglycosides with a general anesthetic or a neuromuscular blockade?

Answer 44

Aminoglycosides will potentiate the neuromuscular blockade

Question 45

What is the withdrawal time for extra-label use of injectable gentamicin in cattle? Neomycin IM, SQ?

Answer 45

18 months for Gentamicin | 240+ days for neomycin IM/SQ

Question 46

Which food animal & disease is IM Gentamicin labeled for use in?

Answer 46

Pigs up to 3 days for colibacillosis (E. Coli)

Question 47

What is the beef label for Gentamicin?

Answer 47

Pinkeye spray

Question 48

Can neomycin be used IM in beef cattle?

Answer 48

NO. Oral only

Question 49

What is the tolerance for Gentamicin residues in cattle?

Answer 49

0

Question 50

What does FARAD stand for?

Answer 50

Food Animal Residue Avoidance and Depletion program

Question 51

What is a physiological event that counterindicates the use of neomycin?

Answer 51

Dehydration