Flashcards in 2: Aminoglycosides, Streptogramins, and Oxazolidinones Deck (52)
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1
core structure of aminoglycosides
1,3-diaminocyclitol linked to one or more aminoglycoside rings
2
name 7 clinically important aminoglycosides
-tobramycin
-kanamycin A
-amikacin A
-gentamicin C2
-neomycin B
-streptomycin
-spectinomycin
3
aminoglycoside MOA
bind 16S rRNA of 30S:
-interferes with formation of initiation complex
-blocks further translation
-elicits premature termination
-impairment of proofreading
-formation of nonsense proteins that impair bacterial cell wall function
-damage membranes, allowing increased transport of drug into cell -> stops protein synthesis completely
4
what do aminoglycosides ultimately lead to?
leakage of ions and disruption of the cytoplasmic membrane, resulting in cell death
5
describe bacterial aminoglycoside uptake
drugs displace Mg2+ and Ca2+ ions that form salt bridges with phosphates of the phospholipids of the membrane
-makes the membrane more permeable
6
passage of aminoglycosides through membrane: active or passive
active transport process
7
three mechanisms of resistance to aminoglycosides
1. metabolism via acetylation, adenylation, phosphorylation
2. 16S rRNA binding site altered via point mutations
3. reduced uptake of drug
8
metabolic resistance to aminoglycosides: describe where each of the processes occurs (on what functional groups)
adenylation and phosphorylation on -OH groups
acetylation on amino groups
9
what are the toxicities of aminoglycosides
irreversible ototoxicity
reversible nephrotoxicity
in large doses- curare-like effects
10
describe aminoglycoside ototoxicity
-tinnitus, high-frequency hearing loss
-vertigo, loss of balance, ataxia
11
how can you monitor ototoxicity during aminoglycoside use
serial audiograms
12
risk factors for ototoxicity with aminoglycosides
-concurrent use of other ototoxic compounds (loop diuretics, vancomycin)
-compromised renal function
-genetic vulnerability
13
name two loop diuretics that can potentiate nephrotoxicity in aminoglycosides
-ethacrynic acid
-furosamide
14
name two nephrotoxic antimicrobial drugs that can potentiate nephrotoxicity in aminoglycosides
-vancomycin
-amphotericin
15
how can you monitor nephrotoxicity during aminoglycoside use
creatinine clearance and dosage decrease
16
what are the curare-like effects you can get with aminoglycosides and how do you reverse them?
respiratory paralysis - can usually be reversed by neostigmine or calcium gluconate (AChEi)
17
what increases likelihood of aminoglycoside toxicity
length of treatment period
18
use of aminoglycosides
both G(+) and G(-)
but almost always reserved for G(-)
19
what are aminoglycosides often paired with
penicillins due to synergism, but they are administered in different compartments to avoid a chemical rxn between the two drugs
20
what are penicillin/aminoglycoside combos used to treat
bacterial endocarditis
21
what is streptomycin most often used to treat
TB
22
what is gentamicin usually used for
UTIs
burns
some pneumonias
joint and bone infections caused by susceptible G(-)'s
23
which aminoglycoside has retained antibacterial activity against resistant strains
amikacin
24
what are the streptogramins
semisynthetic derivatives of a natural mixture of pristinamycin I and pristinamycin II
25
what is synercid a combination of
30% quinupristin
70% dalfopristin
26
why do we not use the parent combination of streptogramins
less suitable solubility for reliable solubility
-the amino side chains of quinupristin and dalfopristin allow salt formation and enhance water solubility
27
synercid: bacteriostatic or bacteriocidal
each component is bacteriostatic on its own, but combination is bacteriocidal
28
how is streptogramin administered
parenterally
29
dalfopristin MOA
directly interferes with peptidyl transferase-catalyzed step of peptide bond formation
30
