Selective toxicity

Question 1

What does selective toxicity require?

What does this depend on?

Answer 1

Exploitable difference between host and pathogen

Depends on evolutionary difference

Question 2

4 mechanisms for antibiotics

Answer 2

Inhibition of cell wall synthesis
Inhibition of protein synthesis
Inhibition of DNA synthesis/replication
Inhibition of bacterial nucleic acids

Question 3

Name the 3 ways antibiotics can effect bacteria

Answer 3

Bacteriostatic = stop growth
Bactericidal = kill but not destroy
Bacteriolytic = kill and remove

Question 4

How do penicillins work?

Answer 4

Virtue of beta lactic ring
inhibits transpeptidase = cross links peptidoglycan (of NAM and NAG)
Inhibits cell wall synthesis

Question 5

How do macrolides work?

Answer 5

Target bacterial ribosome and protein synthesis

Target large subunit and inhibit translocation, stop binding of AA

Question 6

How do tetracylines work?

Answer 6

Target bacterial ribosome and protein synthesis

Target small subunit - stop tRNA binding

Question 7

Mechanism of action of flouriquinolones?

Answer 7

Inhibit topoisomerase, this inhibits DNA replication

Question 8

How do sulphonamides work?

Answer 8

Target biological pathways - folate biosynthesis

Question 9

What virus infects sensory ganglia and becomes latent?

Answer 9

Herpes

Question 10

How is herpes stimulated?

Answer 10

UV light, stress

Question 11

What is the importance of Aciclovir?

Answer 11

First antiviral agent with selective toxicity

Question 12

How does acyclovir select for herpes simplex?

Answer 12

Herpes simplex needs to be phosphorylated for activation
A simplex specific kinase phosphorylates to mono form, then normal cell kinases to tri
Inhibits the simplex specific kinase and inhibits DNA polymerase

Question 13

Why is there and increased incidence of fungal infections in modern society?

Answer 13

Increase use of antibiotics and immunosuppression

Question 14

Name 3 anti-fungals and their mode of action

Answer 14

Azoles, polyenes and mitotic inhibitors
Azoles = inhibit fungal CYP45- reducing ergosterol in membrane and increasing permeability = no replication and less rigidity
Polyenes = bind to sterols in the membrane e9high affinity for ergosterol) and form an ion channel
Mitotic inhibitors = inhibit mitosis by interfering with spindle formation

Question 15

Why are polyenes poorly absorbed? How are they administered?

Answer 15

Lots of PPB
Given orally for GI infections
Otherwise IV