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Aminoglycosides Flashcards

1
Q

Aminoglycosides that end in mycin

A

derived from streptomyces

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2
Q

Aminoglycosides that end in icin

A

derived from another organism or synthetic derivative

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3
Q

Aminoglycosides structure

A

2 hexanose structures on either end and a 2-deoxystreptamine

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4
Q

Aminoglycosides modifications helped to improve

A

activity, prevent resistance, and decrease adverse events

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5
Q

Aminoglycosides structure is unique because it is a

A

nucleophile

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6
Q

Aminoglycosides like to donate

A

electrons

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7
Q

Aminoglycosides is easily modified to

A

an inactive substance

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8
Q

Aminoglycosides MOA membrane penetration:

A
  1. aminoglycoside self promoted uptake process involves drug-induced disruption of Mg2+ bridges between adjacent lipopolysaccharides of gram - bacteria
  2. transport across cytoplasmic membrane is dependent upon electron transport and termed energy dependent phase 1
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9
Q

Aminoglycosides create ____ channels

A

porin

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10
Q

Aminoglycosides MOA involves

A

30s ribosome!

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11
Q

Aminoglycosides MOA (3)

A

blocks initiation of protein synthesis
blocks further translation and elicits premature termination
incorporation of incorrect amino acid

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12
Q

Variables that impact Aminoglycoside activity

A

acidic ph
anaerobic conditions
hyperosmolarity
divalent cations

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13
Q

Aminoglycoside oral absorption

A

poor IV only

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14
Q

Aminoglycoside 1/2 life

A

2-3 hours

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15
Q

Aminoglycoside elimination

A

95% renal

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16
Q

Aminoglycosides are mostly hydrophilic/hydrophobic

A

hydrophilic; does not go well into adipose tissue

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17
Q

Aminoglycosides are eliminated primarily by

A

glomerular filtration

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18
Q

Aminoglycosides are basic/acidic

A

basic

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19
Q

Aminoglycosides have ____ protein binding

A

low

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20
Q

Aminoglycosides penetration into tissues

A

bone
synovial fluid
urine (100x serum)

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21
Q

Aminoglycosides poor penetration into

A 
bronchial secretions
CNS even when inflamed
eye
bile
prostate
purulent fluids
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22
Q

Aminoglycosides have ____ elimination

A

tri-phasic

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23
Q

Aminoglycoside alpha phase (5-15min)

A

distribution of drug from blood to tissues

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24
Q

Aminoglycoside beta phase (2-4hr)

A

elimination of drug through the kidneys

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25
Aminoglycoside gamme phase (150-200hr)
very slow release of drug from tissue binding sites concentration not detectable
26
Aminoglycosides have ____ dependent killing
concentration
27
Aminoglycoside PK/PD parameters
Cmax/MIC ratio or AUC:MIC ratio
28
Aminoglycoside Cmax:MIC preferred
8-10
29
Aminoglycoside dosing regimens
conventional and one daily
30
ODA peak mcg/ml
8-10 x MIC
31
ODA trough mcg/ml
<1
32
Aminoglycosides have a _____ effect even after below MIC concentrations
post antibiotic
33
Aminoglycosides spectrum coverage
light purple: streptococcus, viridans, MSSA, MRSA, e. faecalis, e. faecium dark red: h. influenzae, m. catarrhalis, E. coli, klebsiella, p. mirabilis, morganella, enterobacter, citrobacter, serratia, p. aeruginosa, acinetobacter Misc: synergy for all gram + with cell wall active agent, active against mycobacteria, not active against steno
34
Aminoglycosides are usually given ____ for gram + and usually for endocarditis
synergistically
35
Aminoglycosides used outside of UTI for gram - infections
synergistically also
36
Aminoglycosides are used as | _______ for gram - UTI
mono therapy
37
Aminoglycosides mechanism of resistance
-enzyme modification is most common and plasmid mediated, do not confer resistance to all AG's -decreased uptake through altered transport or impermeable membrane or efflux, cross resistant to all AG's and chromosomally mediated -altered ribosome binding streptomycin requires 1 mutation, other AGs require multiple
38
Aminoglycosides adverse effects
ototoxicity (irreversible) nephrotoxicity neuromuscular blockade (Ca2+ channels)
39
Aminoglycosides nephrotoxicity is called
non-oliguric renal failure (continues to produce urine)
40
There is a ____ rise in serum creatinine with Aminoglycoside nephrotoxicity
slow
41
A small portion of the dose is retained in the ____ lining the proximal tubules after glomerular filtration (Aminoglycoside nephrotoxicity)
epithelial cells
42
After several days of therapy, the AGs induce characteristic _____ of proximal tubular cells consistent with the accumulation of _____.
changes in lysosomes; myeloid bodies
43
Clincally changes in in/out occur | _____ increase serum creatinine
prior to
44
Can also consider ____ as sign of renal damage
proteinuria
45
Aminoglycoside ototoxicity interferes with
hearing (auditory) and balance (vestibular)
46
Rate of occurrence of Aminoglycoside ototoxicity is about
<10%
47
Aminoglycoside ototoxicity occurs due to direct toxic effect on ______ within the inner ear
hair cells
48
Aminoglycoside ototoxicity can occur with _____ dosing and _____ therapy
conventional or QD; during or after
49
There is ___ safe dose
NO
50
Aminoglycoside ototoxicity has ____ correlation with ____ concentrations, but increased risk with sustained high troughs
no; peak and trough
51
Serum AG levels have _______ relationship to levels within the inner ear
no absolute
52
Aminoglycoside vestibulotoxicity is usually _____ although most patients can compensate with visual cues to maintain balance
irreversible
53
Vestibulotoxicity symptoms include
``` disequilibrium ataxia stumbling dizziness loss of balance oscillopsia N/V vertigo nystagmus ```
54
Which AG is the most vestibulotoxic?
gentamicin
55
auditory toxicity results in ___ and _____ frequency hearing loss and is _____
high and low; irreversible
56
Which frequency hearing loss occurs first?
high but may not be recognized clinically
57
AG are RARELY used as
monotherapy
58
AG are usually used in combination to
broader coverage
59
Plazomicin is a
semisynthetic compound
60
Plazomicin is derived from
sisomycin
61
The structure of sisomycin was modified to plazomicin in order to
prevent alterations by AG modifying enzymes
62
Plazomicin has improved in-vitro activity against
aminoglycoside-resistant enterobacteriaceae
63
Plazomicin structure allows it to be potent against enterobacteriaceae including
ESBL AG resistant isolates carbapenem resistant enterobacteriaceae
64
Plazomicin maintains AG characteristics like
inhibits bacterial protein synthesis rapid concentration-dependent activity prolonged post-antibiotic effect
65
Plazomicin oral absorption
poor IV only
66
Plazomicin 1/2 life
3.5 hours
67
Plazomicin elimination
90% renal
68
Plazomicin spectrum coverage
light purple: MSSA, MRSA dark red: h. influenzae, m. catarrhalis, E. coli, klebsiella, p. mirabilis, morganella, enterobacter, citrobacter, serratia light red: p. aeruginosa, acinetobacter Misc: active against gram - with gentamicin resistance especially carbapenemase producing KPC not active against steno poor activity against gentamicin resistant pseudomonas
69
AG (including Plazomicin) dosing: which body weight to do you use when TBW is >25% of IBW?
ABW
70
For AG (including Plazomicin) is renal adjustment necessary?
YES
71
Adverse effects for Plazomicin
``` nephrotoxocity, may be concentrated dependent ototoxicity is assumed to be class effect but not seen in in clinical trials ```
72
Aminoglycosides are bactericidal/bacteristatic
bactericidal
73
The MIC of a pathogen is 2mcg/ml. What peak concentration of tobramycin should be targeted for maximal efficacy? a. 3mcg/ml b. 6mcg/ml c. 12mcg/ml d. 16mcg/ml
d

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