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SilversteinHopper > 177: Aminoglycosides > Flashcards

177: Aminoglycosides Flashcards

1
Q

Are aminoglycosides concentration or time-dependent?

A

concentration dependent

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2
Q

Describe the mechanism of action of aminoglycosides

A

bactericidal
* penetrates bacterial cell wall and membranes
* binds to the 30s ribosomal subunit
* misreading of mRNA ==> production of nonfunctional proteins, detachment of ribosomes from mRNA, cell death

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3
Q

What is the spectrum of aminoglycosides?

A

mostly gram-negative aerobes
some gram-positives
no anaerobes

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4
Q

why do aminoglycosides not work against anaerobic bacteria?

A

uptake across bacterial cell wall depends on energy derived from aerobic metabolism

will not work at low pH or O2 tension environments, e.g.

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5
Q

Should aminoglycosides be considered for animals with abscesses and why

A

no
will not work at low pH or O2 tension environments, e.g., abscesses

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6
Q

What antibiotic group can you combine aminogylcosides with to create synergism and enhanced efficacy, and why

A

beta-lactams
* increase cell permeability
* increases the uptake of aminoglycosides into bacteria

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7
Q

Which has a broader antimicrobial spectrum, gentamicin, or amikacin

A

amikacin

perferred agent for very resistant microbials

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8
Q

Why is monotherapy with an aminoglycoside not appropriate in critically ill animals?

A
  • want synergistic efficacy
  • want other antimicrobial to provide coverage during amino-glycoside free intervals in SDD protocol
  • need to combine with metronidazole or clindamycin for strict anaerobic pathogens
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9
Q

How is the oral bioavailability of aminoglycosides, and what conditions may change this?

A

poor bioavailabilirty
may have significant systemic absorption and toxicity in conditions causing compromised intestinal epithelial barrier

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10
Q

What are 3 criteria your patient should fulfill before starting aminoglycoside therapy?

A
  • adequate hydration
  • stable renal function
  • inactive urine sediment
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11
Q

Do aminoglycosides have a high or low volume of distribution, and how does this affect tissue penetration?

A

highly water soluble with small volume of distribution
poor penetration of biologic membranes

e.g., CSF, prostate, vitreous humor not well penetrated

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12
Q

How are aminoglycosides mainly excreted?

A

through glomerular filtration

< 5% reabsorbed in the tubules

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13
Q

In what tissues do aminoglycosides achieve therapeutic concentrations?

A
  • pleural fluid (nonexudative)
  • peritoneal fluid
  • bones
  • synovial fluid
  • pulmonary parenchyma (not bronchial secretion)
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14
Q

What dosing interval should be used for aminoglycosides. Give 3 reasons for it.

A

single daily dosing protocol
reasons:
* concentration dependent antibiotic
* overcome adaptive resistance
* decreased incidence of toxicities, i.e., mainly nephrotoxicities

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15
Q

What is adaptive resistance?

A

first exposure effect –> down-regulated aminoglycoside uptake by bacteria
* subsequent doses have lower bactericidal effect and shorter postantibiotic effect
* can be prevented by giving subsequent doses after adaptive resistance has passed, i.e., SDD

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16
Q

What measurements need to be taken for therapeutic drug monitoring and at what time should they be taken?

A
  • peak-level blood sample 20-30 min after IV administration
  • trough-level blood sample 2-4 hours before next dose
17
Q

Which measurement, peak or trough level correlates with adverse reactions?

A

trough concentrations

want at least 2-4 hours of drug free intervals

18
Q

Name examples for conditions leading to increased volume of distribution

A
  • vascular leakage
  • edetamous states
  • hypoalbuminemia
  • hyperdynamic states from SIRS
  • mechanical ventilation
  • extensive burn injuries
  • severe trauma

may lead to subtherapeutic serum levels

19
Q

What is the recommended starting dose for gentamicin?

A

6-10 mg/kg q24h

start with low end in cats

20
Q

recommended starting dose for amikacin

A

10-15 mg/kg q24h

start with low end in cats

21
Q

why may IM/SC administration undesirable compared to IV

A
  • associated with discomfort
  • less predictable absorption
22
Q

can you give aminoglycosides through same line/catheter as LRS?

A

No, don’t give with solutions containing Ca

also not with NaHCO3- or heparin

23
Q

Can you give aminoglycosides together with penicillins in the same syringe?

A

No
inactivates aminoglycosides

24
Q

What are the 3 main toxicities caused by aminoglycosides?

A

toxicity to:
* neuromuscular junction
* inner ear apparatus
* kidneys

25
Q

Where in the kidneys do aminoglycosides cause damage?

A

proximal convoluted tubules

26
Q

How do you treat an animal suffering from weakness due to aminoglycoside administration. How commonly do you expect to see this in practice?

A
  • injectable Ca
  • not common, weakness appears at dosages higher than recommended

at risk: animals already suffering from neuromuscular disorders

27
Q

What is the mechanism of action behind ototoxicity by aminoglycosides?

A

accumulates in the cochlear and vestibular apparatus and destroys sensory hair cells

related to duration of treatment, not dose, but not established in SA

28
Q

True or false, aminoglycosides cause anuric kidney failure

A

False, polyuric kidney injury

29
Q

describe how aminoglycosides lead to renal insufficiency

A
  • aminoglycosides have a cationic state ==> will bind to tubular epithelial cells and transported IC via lysosomes
  • lysosomes destabilize and rupture
  • disrupts normal cell structure and function
  • results in decline in glomerular filtration
30
Q

At what day of administration do aminoglycosides have maximum tubular toxicity?

A

around day 9 of therapy

31
Q

Which one is more nephrotoxic, gentamicin or amikacin?

A

gentamicin

32
Q

Why does SDD lead to less nephrotoxicity?

A

uptake of aminoglycosides by tubules appears to be saturable
* less uptake with high but infrequent dosages compared to lower frequent dosages

33
Q

What is more nephrotoxic, amikacin in the morning or at night?

A

at night
circadian rhyhtm may lead to decreased GFR during the night ==> higher incidence of toxicities

this needs more investigation in veterinary medicine

34
Q

true or false, we should measure a renal panel daily to check for aminoglycoside induced renal insufficiency?

A

false, late stage insensitive marker

35
Q

What is the most sensitive marker of aminoglycoside induced renal damage?

A

enzymuria

unfortunately not very practical

36
Q

How do you asses for aminoglycoside induced renal damage?

A

check urine sediment daily for granular or cellular casts
check urine for glucosuria and tubular proteinuria

37
Q

What are risk factors for aminoglycoside induced renal damage?

A
  • older age
  • duration of therapy
  • fever
  • volume depletion or dehydration
  • administration of other nephrotoxic drugs
  • preexisting renal disease
  • K or Mg depletion

SilversteinHopper (11 decks)

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