Aminoglycoside Antibiotics

Question 1

Aminoglycoside antibiotics core structure made of whaT?

Answer 1

1,3 diaminocyclitol linked to one or more aminoglcoside rings

Question 2

Core structures are what?

Answer 2

Streptidine
2-deoxystreptamine
Spectinamine

Question 3

What do aminoglycosides inhibit

Answer 3

Protein biosynthesis

Question 4

How do amino-glycosides inhibit protein biosynthesis?

Answer 4

Binding to 30S ribosomal subunit to the 16S rRNA forming the A site

Question 5

What step of translation does amino-glycodies interfere with?

Answer 5

Formation of initiation complex, causes premature termination

Question 6

What does aminoglycosides form from its interruption of protein synthesis?

Answer 6

Nonsense proteins

Question 7

Result of formation of nonsense proteins due to aminoglycosdies?

Answer 7

Cell wall function impaired

Question 8

Result of impaired cell wall function in aminoglycosides?

Answer 8

More aminoglycosides (AMG) gets in and stops protein synthesis altogether

Question 9

AMG positively charged or negatively?

Answer 9

Positively

Question 10

What needs to be displaced to get AMG in through outer membrane?

Answer 10

Mg++ and Ca++ ions

Question 11

Why does Mg and Ca need to be displaced?

Answer 11

They form salt bridges with phosphates of phospholipids

Question 12

What type of transport process is passage through cytoplasmic membrane?

Answer 12

Active transport

Question 13

How many bacterial resistance mechanisms have evolved to combat AMG?

Answer 13

At least 3

Question 14

What are the 3 mechanisms that resist AMG?

Answer 14

1) Metabolism
2) Altered Ribosomes
3) Altered AMG uptake

Question 15

How does the metabolism resistance of AMG work?

Answer 15

Bacteria inactivate AMG by acetylation, adenylation, and phosphorylation

Question 16

Are AMGs metabolized by humans or bacteria?

Answer 16

Bacteria

Question 17

How does altered ribosome resistance work?

Answer 17

16S rRNA binding site via point mutations

Question 18

Which bacteria has displayed altered ribosomes in the past?

Answer 18

Mycobacterium tuberculosis

Question 19

How does Altered AMG uptake resistance work?

Answer 19

Emergence is far less than resistance due to metabolism

Question 20

Dangers of AMG?

Answer 20

Ototoxic and nephrotoxic

Question 21

Difference between Ototoxicity and nephrotoxicity in AMG?

Answer 21

Ototoxicity is irreversible while nephrotoxicity is reversible

Question 22

Risk factors for ototoxicity?

Answer 22

Using other ototoxic drugs
Reduced renal function
Genetic vulnerability

Question 23

A less common effect that can result from large doses of AMGs?

Answer 23

Curare like effect involving respiratory paralysis

Question 24

How does one deal with the respiratory paralysis caused by AMG?

Answer 24

Neostigmine

Calcium gluconate

Question 25

What is the period treatment that AMGs should be discontinued after?

Answer 25

5 days

Question 26

Spectrum of antibiotics for AMGs?

Answer 26

Gram + and gram -

Question 27

Primary use for AMGs?

Answer 27

Gram -

Question 28

What are AMGs usually used in combination with?

Answer 28

Penicillin

Question 29

How does AMG and Penicillin combo need to be given?

Answer 29

One in each arm to avoid chemical reaction between the two

Question 30

Streptomycin used to treat what?

Answer 30

Tuberculosis

Question 31

Most important of the AMGs?

Answer 31

Gentamycin

Question 32

Which AMG used for nosocomial infections?

Answer 32

Amikacin

Question 33

Streptogramin is a semisynthetic structure derived from what?

Answer 33

Pristinamycin 1 and pristinamycin 2 taken from Strep pristinaspiralis

Question 34

Synercid mixture contains what?

Answer 34

30% quinupristin | 70% Dalfopristin

Question 35

Dalfopristin interfere with protein synthesis how?

Answer 35

Interfere with peptide transferase formation of peptide bond between two amino acids

Question 36

How does Quinupristin work?

Answer 36

Binds n the ribosomal tunnel and blocks it

Question 37

What provides resistance to Streptogramin?

Answer 37

Mutation of A2062 which gates the tunnel exit

Question 38

What is Synercid used IV in treatment of?

Answer 38

Vancomycin resistant Enteroccus faecium bacteremia Skin infection via MRSA Vanco resistant Enteroccus faecium urinary tract infections

Question 39

Most common resistance to quinupristin due to?

Answer 39

Adenine methylation of A2058 in 23S rRNA

Question 40

Streptogramin treatment most likely reserved for what?

Answer 40

Life threatening Gram +

Question 41

Senesced use selects for resistant forms of?

Answer 41

E. faecialis E. faecium S. aureus

Question 42

Toxicity due to synercid?

Answer 42

None

Question 43

Does Synercid penetrate blood brain barriers?

Answer 43

No

Question 44

Where is concentration of Synercid 50X the extracellular fluid concentration?

Answer 44

Macrophage

Question 45

How is Synercid excreted?

Answer 45

75% biliary excretion

Question 46

Streptogramins inhibit what enzyme?

Answer 46

CYP3A4

Question 47

How does linezolid inhibit protein synthesis?

Answer 47

It stops the formation of the 70S initiation complex

Question 48

What is Linezolid used to treat?

Answer 48

1) Vanco resistant Enterococcus faecium 2) Nosocomial pneumonia caused by MRSA 3) Skin infections caused by MRSA

Question 49

How is Linezolid taken?

Answer 49

Orally or I.V

Question 50

When is linezolid taken?

Answer 50

Infections caused by multiple drug resistant Gram +

Question 51

Where has linezolid resistance been reported?

Answer 51

Enterococcus species

Question 52

How do organisms develop resistance against linezolid?

Answer 52

Target site modification, G to U substitution in peptidyl transferase center

Question 53

What can happen if a patient takes linezolid for more than 6 months?

Answer 53

Neuropathy

Question 54

Half life of linezolid?

Answer 54

4-6 hour

Question 55

What does Linezolid inhibit non selectively?

Answer 55

Monoamine oxidase

Question 56

Lienzolid has potential for interaction with whaT?

Answer 56

Adrenergic and serotonergic agents

Question 57

Patients should avoid consuming what when taking Linezolid?

Answer 57

Food/beverages rich in tyramine