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Pharmacology II > Aminoglycosides > Flashcards

Aminoglycosides Flashcards

1
Q

What are the aminoglycosides?

A

Neomycin, Kanamycin/Amikacin, Gentamicin

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2
Q

Are the aminoglycosides hydrophilic or hydrophobic?

A

Highly hydrophilic, lipid insoluble

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3
Q

How well are aminoglycosides absorbed from the gut?

A

Not well. 3 - 5%

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4
Q

Do aminoglycosides bind to plasma protein?

A

Not well. But bind readily to cellular debris

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5
Q

How do aminoglycosides work?

A

Protein synthesis inhibition

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6
Q

At what pH do aminoglycosides work best?

A

7.5 - 8.0

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7
Q

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

A

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

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8
Q

Why do aminoglycosides not penetrate bacteria well?

A

Hydrophilic nature

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9
Q

What are the 2 things that bacteria penetration relies on?

A

Energy dependent phase 1 (oxygen dependent)

Energy dependent phase II (disruption of cytoplasmic membrane)

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10
Q

What can block energy dependent phase 1 of aminoglycosides?

A

Hyperosmolarity, low pH, anaerobic conditions

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11
Q

Why are aminoglycosides bactericidal?

A

Energy dependent phase II disrupts cytoplasmic membrane and causes ion leakage

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12
Q

What is the spectrum of aminoglycosides?

A

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

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13
Q

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

A

Mostly staph. Some Streptococcus sp but many resistant

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14
Q

Which gram- bacteria are aminoglycosides used for?

A

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

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15
Q

Why are aminoglcyosides not useful against gram- anaerobic?

A

Oxygen depedent, energy depdent phase I

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16
Q

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

A

Resistant to enzymes produced by enterobacteriaceae

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17
Q

Which aminoglycoside has the broadest spectrum?

A

Amikacin

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18
Q

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

A

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

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19
Q

What route can aminoglycosides be given?

A

IV, IM, SC

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20
Q

Can you give aminoglycosides orally? If so, when?

A

Only when activity is targeted for GI tract

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21
Q

Why are aminoglycosides poorly absorbed from GI tract?

A

Poorly lipid soluble

22
Q

Do aminoglycosides have a high or low Vd?

A

Very low because of hydrophilic nature

23
Q

Can aminoglycosides penetrate the CNS?

A

Not really

24
Q

Why are aminoglycosides more widely distributed in neonates?

A

High amount of extracellular fluid

25
Q

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

A

Renal cortex & cochlear tissue

26
Q

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

A

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

27
Q

What are the elimination half times of aminoglycosides?

A

Short, 1 - 3 hours

28
Q

What is the primary route of excretion for aminoglycosides?

A

Kidneys via parent compound

29
Q

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

A

Urine 100:1 serum

30
Q

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

A

Can diffuse back to plasma & prolong residues

31
Q

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

A

8 - 10x MIC of target pathogen

32
Q

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

A

Once a day

33
Q

Why are aminoglycosides dosed only once a day?

A

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

34
Q

Should you administer aminoglycosides by a constant IV infusion?

A

No!

35
Q

Which aminoglycoside is the most nephrotoxic?

A

Neomycin

36
Q

Can you use neomycin for systemic use?

A

NO. Nephrotoxicity

37
Q

List aminoglycosides in order of nephrotoxicity (least to most)

A

Amikacin < Gentamicin < Neomycin

38
Q

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

A

Diuretics. They increase nephrotoxic potential.

39
Q

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

A

Decrease nephrotoxicity

40
Q

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

A

Bimodal. First phase is nonazotemic followed by azotemic

41
Q

Will cessation of aminoglycosides stop azotemia from progressing?

A

No

42
Q

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?

A

Cats, vestibular

Dogs experience auditory

43
Q

Will renal toxicity or ototoxicity occur first?

A

Renal before substantial ototoxicity

44
Q

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

A

Aminoglycosides will potentiate the neuromuscular blockade

45
Q

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

A

18 months for Gentamicin

240+ days for neomycin IM/SQ

46
Q

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

A

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

47
Q

What is the beef label for Gentamicin?

A

Pinkeye spray

48
Q

Can neomycin be used IM in beef cattle?

A

NO. Oral only

49
Q

What is the tolerance for Gentamicin residues in cattle?

A

0

50
Q

What does FARAD stand for?

A

Food Animal Residue Avoidance and Depletion program

51
Q

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

A

Dehydration

Pharmacology II (15 decks)

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