Public: Antimicrobial Chemotherapy

Question 1

Briefly describe Ehrilch’s influence with regards to syphilis

Answer 1

Syphilis=STD
Caused by spirochaete bacterium Treponema pallidum
Without treatment it damages the heart, brain and nervous system, hence fatal
-Ehrilch and his team led the first organized team effort to optimize the biological activity of a lead compound through systematic chemical modifications
Aimed to treat sleeping sickness, but cured syphilis instead with,,
Salvarsan

Question 2

Use of Neosalvarsan

Answer 2

Available in 1912 to treat syphilis
Used until the development of penicillin in the 1940s
Used rather than salvarsan as more water soluble and less toxic

Question 3

Describe the mechanism of action of Salvarsan

Answer 3

Salvarsan is a pro-drug, metabolized slowly to produce oxophenarsine which was used clinically in the 1930s
Oxophenarsine reacts with thiol groups in proteins. causing denaturisation

Question 4

Thiol group?

Answer 4

R-S-H

Question 5

Name 6 bacterial targets for selective inhibition

Answer 5

• Cell wall (human cells do not have them)
• Cell membrane (different composition)
• DNA synthesis
• Transcription
• Protein synthesis in the cytoplasm (70S not 80S ribosomes)
• Other metabolism features

Question 6

Name 2 types of drugs that attack bacterial cell wall synthesis?

Answer 6

Vancomycin and beta-lactams

Question 7

What is vancomycin like structurally?

Answer 7

• A non ribosomal peptide
• Many unusual amino acids
• Glycosylated
• Discovered in jungles of Borneo
• Product of the soil MO Amycolatopsis orientalis

Question 8

How does vancomycin interfere with cell wall synthesis?

Answer 8

Prevents cell wall peptides interacting with one another and forming cross-links

Question 9

Name some uses of vancomycin?

How is it administered?

Answer 9

Gram positive infections only as does not cross gram negative cell wall
Normally injected as the digestive system is designed to hydrolyse peptide bonds
Injected rifampicin-vancomycin combiniation is the preferred choice by many rusts for treatment of MRSA
But many do not recommend vancomycin alone

Question 10

Use of oral vancomycin?

Answer 10

Clostridium difficile infections

Question 11

3 reasons side effects of vancomycin may have been exaggerated?

Answer 11

• early preparations of vancomycin were astonishingly impure
• People who reported nephrotoxicity were generally found to be taking other nephrotoxins
• Ototoxiciy seems quite rare

Question 12

Define ototoxicity

Answer 12

Toxicity affecting the ear

Question 13

Name a glycopeptide used as an alternative to vancomycin

Answer 13

Teicoplanin

Mode of action believed to be similar

Question 14

Vancomycin resistance…

When was it first reported in the UK?

Answer 14

1999