Flashcards in Public: Antimicrobial Chemotherapy Deck (14):
Briefly describe Ehrilch's influence with regards to syphilis
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,,
Use of Neosalvarsan
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
Describe the mechanism of action of Salvarsan
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
Name 6 bacterial targets for selective inhibition
-Cell wall (human cells do not have them)
-Cell membrane (different composition)
-Protein synthesis in the cytoplasm (70S not 80S ribosomes)
-Other metabolism features
Name 2 types of drugs that attack bacterial cell wall synthesis?
Vancomycin and beta-lactams
What is vancomycin like structurally?
-A non ribosomal peptide
-Many unusual amino acids
-Discovered in jungles of Borneo
-Product of the soil MO Amycolatopsis orientalis
How does vancomycin interfere with cell wall synthesis?
Prevents cell wall peptides interacting with one another and forming cross-links
Name some uses of vancomycin?
How is it administered?
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
Use of oral vancomycin?
Clostridium difficile infections
3 reasons side effects of vancomycin may have been exaggerated?
-early preparations of vancomycin were astonishingly impure
-People who reported nephrotoxicity were generally found to be taking other nephrotoxins
-Ototoxiciy seems quite rare
Toxicity affecting the ear
Name a glycopeptide used as an alternative to vancomycin
Mode of action believed to be similar