JAL L2 Antimicrobials

Question 1

Define antimicrobials

Answer 1

chemicals which kill or inhibit microbial growth

Question 2

Sources of antimicrobials? 3

Answer 2

microorganism
synthese
semisynthesis* (most common)

Question 3

Most antimicrobials kill only …….. bacteria

Answer 3

actively growing

Question 4

Ideal antimicrobial properties: 3

Answer 4

selective activity
cidal activity
slow emergence of resistance

Question 5

ideal pharmacological properties of antimicrobials: 6

Answer 5

• non toxic
• long t1/2
• good tissue distribution
• low protein binding
• oral & parenteral
• no interactions

Question 6

4 sites of antimicrobial action

Answer 6

cell wall
cell membrane
nucleic acid synthesis
protein synthesis

Question 7

inhibitors of cell wall synthesis inhibit synthesis of…

Answer 7

peptidoglycan

Question 8

What type of bond is found in peptidoglycan

Answer 8

glycosidic

Question 9

Initial step of peptidoglycan synthesis

Answer 9

D-Ala-Ala bonds to AA side chain to form pepto peptide

Question 10

What does pentopeptide attach to that carries if to the exterior of the cell

Answer 10

Bactoprenol c55 lipid carrier.

Question 11

PG cross linking via amino acid side chain requires…. (2)

Answer 11

transpeptidases

Loss of terminal AA from the side chain

Question 12

β-Lactam have what common structure

Answer 12

β-Lactam ring (square with =O off bottom left and N at bottom right corner)

Question 13

what do β-Lactam bind to?

Answer 13

Penicillin binding proteins (transpeptidases)

Question 14

What do penicillin binding proteins normally do?

Answer 14

x-link

so β-Lactam binding prevents x-linking

Question 15

What does β-Lactam mimic to bind….

Answer 15

D-Ala-D-Ala - so they get incorporated into the cell wall.

Question 16

What does incorporation of β-Lactam into the cell wall caus?

Answer 16

autolysins to break down the cell wall

Question 17

Are β-Lactam more effective on gram negative of gram positive?

Answer 17

negative (as they get trapped between the outer and cytoplasmic membrane and therefore higher conc)

Question 18

2 e.g. of glycopeptides?

Answer 18

teicoplanin

vancomycin

Question 19

how do glycopeptides work? (2)

Answer 19

1. binds to terminal D-Ala-D-Ala. Prevents transglycosylase enzyme from adding PG monomer onto glycan chain.
   (cannot lose terminal D-Ala-D-Ala to provide energy for cross linking)
2. prevents x linking

Question 20

2 e.g. of polymyxins

Answer 20

polymyxin C, polymyxin E (colistin)

Question 21

Where do polymyxins act?

Answer 21

at the cell membrane

Question 22

Polymyxins work on gram positive or negative?

Answer 22

ONLY gram negative as they bind to outer membrane for effect.

Question 23

How do polymyxins work?

Answer 23

Disrupt the membrane causing leakage of cytoplasmic contents.

Question 24

What class of antimicrobials acting on Nucleic Acid Synthesis are ‘Metabolic inhibitors of NA synthesis’? (2)

Answer 24

Sulphonamides

Trimethoprim

Question 25

What class of antimicrobials acting on Nucleic Acid Synthesis ‘Affect DNA replication’?

Answer 25

Fluoroquinolones

e.g. ciprofloxacin and levofloxacin

Question 26

What class of antimicrobials acting on Nucleic Acid Synthesis ‘Affect RNA polymerase’?

Answer 26

Rifamycins

Question 27

What class of antimicrobials acting on Nucleic Acid Synthesis ‘Affect DNA’?

Answer 27

Nitroimidazoles

Question 28

How do Fluoroquinolones work?

Answer 28

Reduce Type II DNA gyrase AND/OR Type IV topoisomerases.

Question 29

What does Type II DNA gyrase normally do?

Answer 29

removes DNA supercoils ahead of replication fork

Question 30

What does Type IV topoisomerase do?

Answer 30

separates DNA after replication

Question 31

Inhibitors of protein synthesis tend to be static or cidal?

Answer 31

Static

Question 32

Why more s/e with inhibitors of protein synthesis?

Answer 32

Similar process for eu and prokaryotes

Question 33

What class is gentamycin?

Answer 33

Aminoglycoside

Question 34

What class is linezolid?

Answer 34

Oxazolidinones

Question 35

Where do aminoglycoside bind to act?

Answer 35

on the 30S subunit.
Work by reducing initiation and assembly of the ribosome,
Reduce binding and assembly of tRNA in A site and translocation

Question 36

Where do oxazolidinones and SOME aminoglycoside bind to act?

Answer 36

50S subunit.

Reduce assembly of the initiation complex

Question 37

Where to tetracyclines bind to act?

Answer 37

30S subunit of ribosome, reduce binding of tRNA in A site

Question 38

Where does chloramphenicol bind to act?

Answer 38

50S subunit

reduces peptide bond formation

Question 39

Where do macrolides bind to act?

Answer 39

50S subunit

reduce translocation and release of tRNA

Question 40

Where does fusidic acid bind to act?

Answer 40

EF-G complex

to reduced translocation of tRNA from A to P site