ANTIBACTERIAL CHEMOTHERAPY 🦠🪱

Question 1

Which 4 classes of antibacterials contain B-lactam ring?

Answer 1

Penicillins
Cephalosporins
Monobactams
Carbapenems

Question 2

Penicillins

Why do we need to decrease acid susceptibility?

Answer 2

The 4 membered ring (b lactam ring) is very strained, we need groups around the b lactam ring that will make the ring susceptibility to acid hydrolysis

Question 3

Examples of how sensitivity to acid is overcome:

Answer 3

1. Flucloxacillin:
   The introduction of an electronic withdrawing group on the amide side chain
2. Amoxicillin:
   Intro of a bulky group on the amide side chain

Question 4

Explain the difference between
Intrinsic resistance and
Acquired resistance

Answer 4

Intrinsic resistance:
Natural resistance an organism has to be an antibiotic

Acquired resistance: due to chance mutation in genetic material or the acquisition of resistance genes

Question 5

How do Penicillins disrupt peptidoglycan formation?

Answer 5

B lactams interfere with peotidoglycan formation through their interaction with the Penicillin Binding Proteins.

Question 6

Penicillin MOA

Answer 6

Bind covalently to active site of enzyme, preventing access of peotidoglycan and attack of OH group on D-Ala

Question 7

Cycloserine MOA

Answer 7

Question 8

Resistance of cyclosterine related to?

Answer 8

Over production of D-Ala racemase

Question 9

Resistance of Vancomycin related to?

Answer 9

1. VRE: Vancomycin Resistant Enterococci: produces a D-Ala-D-Lactate lipase which synthesises an ester (D-Ala-D-Lac) rather than an amide (D-ALA-D-ALA)
2. MRSA:
   Due to plasmid (blaZ) mediated b-lactamase AND
   A Chromosomal (mecA) gene which was acquired from an unknown bacterium which encodes for an altered penicillin binding protein (PBP 2a)
   PBP 2a has decreased affinity for binding b lactams

Question 10

Daptomycin

MOA > cell wall

Answer 10

Insertion of daptomucin into the lipid bilayer, facilitated by thr lipid tail, promoting weak.hydrophobic interactions with phospholipd bilayer

Question 11

Resistance of Daptomycin

Answer 11

Point mutations in mprF and yyvG genes.

mprF enzyme influences the nature of the phospholipid content

yycG thought to be involved in cell permeability

Question 12

Quinolones
MOA

Answer 12

Inhibit bacterial DNA gyrase snd topoisomerase IV

Question 13

What do Quinolones target in Gram positive and Gram negative bacteria?

Answer 13

Gram positive = topoisomerase IV

Gram negative = DNA gyrase

Question 14

Resistance of Quinolones?

Answer 14

Decreased accumulation of the quinolones in cells due to the impermeability of the membrane OR

the over expression of effluxion pumps.

Question 15

Sulphonamides

Class
Moa

Answer 15

Antifolates= interfere with the bacterial biosynthesis of folic acid.

The sulphonamide group and a free amino group at the para position were found to be essential

Question 16

How does sulphonamides prevent formation of folic acid?

Answer 16

Question 17

Resistance of Sulphonamides

Answer 17

Chromosomal resistance through resistance of folP gene in E.coli, S.aureus leads to alterations in the sulphonamide binding site of the DHPS

Question 18

Trimethoprim (monotrim, proloprim)

Class

Answer 18

Antifolate agent = DHFR inhibitor

Question 19

Agents which target protein synthesis?

Answer 19

Chlorqmphenicol, tetracyclines, erythromycin

Question 20

Chloramphenicol

MOA

Answer 20

Chloramphenicol binds to large ribosome subunit (50S) at the peptidyl transferable centre A site, preventing binding of the next changed tRna.

Question 21

Which isomer form of Chloramphenicol is active?

Answer 21

Only the R,R- isomer is active

Question 22

Indications of use of chloramphenicol

Answer 22

Treatment of meningitis in patients with b lactam allergies

Not given systemically as severe toxicity..
Used in treatment if bacterial conjunctivitis

Question 23

Resistance of chloroamohenicol

Answer 23

Resistant to pseudomonas = due to effluxion pumps.

CAT enzyme which acetylayes chloramphenicil- so it no longer binds to the PTC a site.

Question 24

Aminoglycosides (-sidal)

MOA

Answer 24

Bind to RNA because of interactions with phosphate backbone and hydrogen binding = causes adenines to flip out.
Causes incorporation of incorrect amino acids

Question 25

Resistance of aminoglycosides

Answer 25

Resistance due to

Decrease uptake of increased effluxion
And
Mutations of ribosome= methylation of ribosome decreasing binding affinity of the aminoglycosides

Question 26

Which antibacterials are TIME DEPENDANT?

Answer 26

B lactams =
Need to be in contact with PBPs for sufficient amount of time to interfere with cell wall synthesis

Macrolides

Question 27

Which antibacterial is CONCENTRATION dependant?

Answer 27

Aminoglycosides.

Question 28

Linezolid

Moa

Answer 28

Binds to PTC A site, disrupting the binding of the next changed trna

Question 29

Linezolid

Resistance

Answer 29

Gram negative bacteria = resistance due to efficient bacterial effluxion pumps

Gram positive bacteria = resistance due to decreased linezolid uptake

Question 30

Macrolids: erythromycin

How is acid instability of erythromycin overcome?

Answer 30

By use of entering costings so that drug us only released in the higher pH of the small intestines.

Question 31

Macrolides

Resistance

Answer 31

Due to modifications to the ribosome

Resistance to streph: caused by constitutive erm.

Question 32

Isoniazid

Resistance

Answer 32

Mycobacterium TB LINKED TO:

Mutatuons/deletions in the KatG gene regulatory region.

Question 33

Resistance summary