Lecture 4 Aminoglycosides/Synercid/Linezolid

Question 1

What are the 2 “core structures” of the aminoglycosides?

Answer 1

streptidine; 2-deoxystreptamine

Question 2

Aminoglycosides (AGs) are bacterio______

Answer 2

cidal

Question 3

AG mechanism:

binds the ____ of the ____ ribosomal subunit in the ____ site, interfering with formation of the _______ _____

Answer 3

16sRNA; 30s

A; initiation complex

Question 4

AG mechanism:

inhibits translation by preventing translocation of the _____ from the ____ to the ____ site, causing premature ______

Answer 4

peptidyl-tRNA;
A, P;
termination

Question 5

AG mechanism:

Impairs the _____ mechanism, causing _____ mutations which end up forming _____ proteins.

Answer 5

proofreading; frameshift

nonsense

Question 6

AG mechanism:

Nonsense proteins damage the _____ _____, increasing ____, and allowing more AGs to enter

Answer 6

cell membrane;

permeability

Question 7

Entry of the _____ly charged AGs through the outer membrane involves the displacement of ____ and ____ ions that form ____ _____ with phosphates of phospholipids in the membrane, increasing permeability

Answer 7

positive;
Mg, Ca;
salt bridges

Question 8

Passage of AGs through the cytoplasmic membrane is an ______ transport process and requires _____.

Answer 8

active; O2

Question 9

AG Resistance:

1. _______
2. _______
3. ______

Answer 9

Metabolism, ribosome mutations, altered uptake

Question 10

AG resistance–> metabolism:

Bacteria can _____, _____, or _____ AGs, inactivating them. These genes responsible can be transferred to other _____

Answer 10

adenylate, acetylate, phosphorylate;

bacteria

Question 11

AG side effects:

Irreversible _____ and reversible ______.

Answer 11

ototoxicity; nephrotoxicity

Question 12

AG side effects:
Ototoxicity/Nephrotoxicity is increased with concurrent use of other ototoxic drugs such as vancomycin and ______ diuretics. Compromised ______ function also increases risk

Answer 12

loop;

renal

Question 13

How to monitor ototoxicity:

How to monitory renal toxicity:

Answer 13

serial audiograms;

creatinine clearance

Question 14

____-like effects are less common with AG use but can occur with large ____

Answer 14

Curare; large

Question 15

Generally, AG’s are used for severe (Gram +/Gram -) (Aerobic/Anaerobic) bacterial infections

Answer 15

Gram -; aerobic

Question 16

AG’s are synergistic with ______. However, these should not be administered within the same _____, due to a chemical rxn that inactivates both drugs.

Answer 16

Penicillin (and other beta lactams)

compartment

Question 17

____ is the AG that is most often used to treat Tb.

Answer 17

Streptomycin (although not much anymore)

Question 18

_____ is the most important of the AGs, according to his notes

Answer 18

Gentamycin

Question 19

AG-resistant strains are common in hospitals, but _____ has retained activity against these strains and is the drug of choice for _____ infections

Answer 19

Amikacin; nosocomial

Question 20

What is Synercid a mixture of?

Answer 20

Quinupristen, dalfopristin

Question 21

Quinupristin and dalfopristin separately are bacterio_____. Synercid is bacterio____

Answer 21

static;

cidal

Question 22

Quinu- and dalfopristin are derived from ______. _____ lacks suitable solubility for reliable dsoes

Answer 22

pristinamycin; pristinamcyin

Question 23

Both Quinu- and dalfo- bind the __s RNA

Answer 23

23

Question 24

Dalfopristin binds and inhibits ____ ____

Answer 24

peptidyl transferase

Question 25

Quinupristin binds and blocks the ____ _____

Answer 25

ribosomal tunnel

Question 26

Quinupristin and dalfopristin belong to the _____ family

Answer 26

streptogramins

Question 27

Synercid is used for vancomycin resistant enteroccus ____ bacteremia and UTIs as well as skin infections caused by _____

Answer 27

faecium;

MRSA

Question 28

The most common resistance to quinupristin is due to adenine _____ of the A2058 ____s rRNA. This renders synercid _______

Answer 28

methylation; 23s

bacteriostatic

Question 29

75% of clearance of Synercid is through _____ excretion

Answer 29

biliary (Fecal matter)

Question 30

Streptogramins inhibit ______

Answer 30

CYP3A4 (cyp for warfarin, cyclosporine, NNRTIs)

Question 31

______ is an example of an oxazolidinone

Answer 31

linezolid

Question 32

Linezolid mech:

binds the ____s rRNA of the ____s ribosomal subunit

Answer 32

23s; 50s

Question 33

Linezolid mechanism:
binds the 50s ribosomal subunit before formation of the _____ ribosome; ie before interaction of the 50s ribosomal subunit, the 30s ribosomal subunit, and _____-tRNA

Answer 33

70s;

fMet-

Question 34

Linezolid is typically only used to treat Vanc resistant _______ and nosocomial pneumonia/skin infections caused by ______

Answer 34

enterococcus faecium;

MRSA

Question 35

Resistance to linezolid is due to ____ mutations of the _____ ____ of the 23s rRNA

Answer 35

point;

binding site

Question 36

Side effects of linezolid include thrombo_______, bone marrow ______, and peripheral ______

Answer 36

cytopenia; supression; neuropathy

Question 37

Linezolid is a reversible, non-selective inhibitor of _________

Answer 37

monamine oxidase

Question 38

Linezolid can interact with adrenergic and serotonergic agents, causing ______

Answer 38

serotonin syndrome

Question 39

Patients taking linezolid should not consume large quantities of food containing ______ in order to avoid a significant _____ response

Answer 39

tyramine;

pressor