SF - anti-bacterials

Question 1

Describe the structure of peptidoglycans.

Answer 1

Chains of amino sugars with tetrapeptide side chains. The tetrapeptide side chains are joined by peptide cross links.

Question 2

How do B-lactams function?

Answer 2

Prevents the cross links joining to the tetrapeptide side chains.

Question 3

What are the anti-bacterials that are classed as B-lactams?

Answer 3

Penicillin
Cephalosporin
Methicillin etc.

Question 4

What does the effect of B-lactam antibiotics depend on?

Answer 4

Ability to bind to penicillin binding proteins, which are a subgroup of transpeptidases.
Drug access to transpeptidases. Gram +ve LPS hinders drug passage.
Stability against B-lactamase activity.

Question 5

What are B-lactamases and what is their function?

Answer 5

Family of enzymes produced by bacteria.

They hydrolyses the B-lactam ring, which reduces the effectiveness of B-lactam anti-biotics.

Question 6

What are the uses of clavulanic acid?

Answer 6

B-lactamase inhibitor.

There is no effect if it is administered alone, so is given alongside a b-lactam anti-biotic.

Question 7

What is the route of administration of benzylpenicillin and why?

Answer 7

IV. It cannot be given orally due to it’s instability in acid.

Question 8

What are the limitations of benzylpenicillin?

Answer 8

Narrow spectrum of activity.
Gram+ve and cocci.
Broken down by B-lactamase.

Question 9

What are the advantages of semi-synthetic penicillin use?

Answer 9

Increased stability to acids.
Decreased susceptability to B-lactamase.
Increased activity against gram -ve bacteria.

Question 10

What are the differences in ribosomal structure between mammals and bacteria/mito? Why is this beneficial?

Answer 10

Mammalian 80s: 60s + 40s
Bacterial/mito 70s: 50s + 30s

These structural differences allows for drug preference.

Question 11

What is the mechanism of tetracyclines?

Answer 11

Competes with tRNA for the A site.

Question 12

What is the mechanisms of aminoglycosides?

Answer 12

Misreading of messages. Wrong tRNA binds to ribosomal complex or incorrect AA added to the chain.

Question 13

What is the mechanism of chloramphenicol/florfenicol?

Answer 13

Peptide bond formation

Question 14

What is the mechanism of macroides?

Answer 14

Inhibition of translocation.

Question 15

What reaction and enzyme does sulfonamides inhibit?

Answer 15

PABA -> folate

Dihydropterase synthetase

Question 16

What reaction and enzyme does trimethoprim inhibit?

Answer 16

Folate -> tetrahydrofolate

Dihydrofolate reductase

Question 17

Why do sulfonamides only affect bacterial cells?

Answer 17

Mammalian cells do not synthesise folate.

Question 18

Why does trimethoprim affect bacterial cells more?

Answer 18

More sensitive to the bacterial enzyme dihydrofolate reductase.

Question 19

How can bacterial resistance be aquired?

Answer 19

Mutations - chromosomal determinants.
Plasmids - extrachromosomal determinants.
Transposons - transfer of genes between genetic elements within the bacterium.
Transformation/conjugation/transduction - transfer of genes between bacteria.

Question 20

How can bacteria cause drug inactivation?

Answer 20

B-lactamase, although the use of clavulanic acid could prevent this.
Resistance could be expressed on chromosomes or plasmids. Chromosomal resistance can be induced, where as plasmid resistance is constitutively expressed.

Question 21

Resistance to which antibacterials can lead to alterations of the drug binding site?

Answer 21

Erythromycin -> mutation of 50s subunit

Quinolones -> mutation of DNA gyrase

Question 22

What mechanism of bacteria leads to decreased drug accumulation?

Answer 22

Increased number of efflux pumps.

Particularly an issue with tetracyclines, so therapeutic use has been greatly reduced.