2: Aminoglycosides, Streptogramins, and Oxazolidinones Flashcards Preview

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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

quinupristin MOA

binds in the ribosomal tunnel and causes blockage of the tunnel
"constipation of the ribosome"