antivirals and antimicrobial Flashcards
what is glutathione?
an endogenous antioxide
also used in drug metabolism to conjugate polar groups
what happens if there is too much drug to detox?
glutathione used up – build up NAPQI – toxic – liver kills you – jaundice
how do you develop antiviral and antimicrobial drugs?
look at the life cycle, how does it get into the cell, how is it processing itself and how is it released - find a way to block
what is HIV viral attachment and entry blocked by?
enfuvirtide and maraviroc
what is HIV penetration blocked by?
interferon alpha - HBV, HCV
which drug stops the influenza virus from being released?
neuraminidase inhibitors
what does acyclovir do?
blocks nucleic acid synthesis
what is acyclovir
a guanosine analogue
what makes the virus more susceptible to acyclovir than the host?
Herpesvirus-encoded thymidine kinase encoded in the viral genome phosphorylates acyclovir 100 fold faster than the host cell enzyme does
what converts the monophosphate to do/triphosphate forms
host kinases
what does acyclovir triphosphate do? (AcTP)
outcompetes deoxyguanosine triphosphate as the substrate for DNA polymerase infections - then incorporated into viral DNA - premature DNA chain termination
what is the structural difference between acyclovir and guanosine
acyclovir has just an O where guanosine has a rind
what are the 7 stages of the HIV virus life cycle?
- binding/attachment
- fusion
- reverse transcription
- integration
- replication
- assembly
- budding
where in the life cycle does maraviroc target
the binding
where in the life cycle does enfurivirtide target
fusion
how does Nevirapine target HIV virus?
it is a non-nucleotide reverse transcriptase inhibitor
how does AZT target HIV virus?
nucleotide reverse transcriptase inhibitor
where in the life cycle does dolutegravir target
integration into the host DNA
where in the life cycle does amprenavir target
it is a protease inhibitor
-the protease acts to break up the long protein chain that form the immature virus
what is are the main components of bacterial cell membrane?
ergosteroids, mycolic acids
what do ahminoglycosides names end
-mycin
kanamycin,vancomycin
what do aminoglycocide and B lactase target
cell wall synthesis
inhibitors of bacterial metabolism
sulphonamides and trimethoprim
inhibitors of cell wall synthesis bacteria
ahminoglycosides (vancomycin…), B lactams
which antimicrobials inhibit protein synthesis
tetracyclines, aminoglycosides, macrolides and chloramphenicol
Rifamycin
nhibits prokaryotic DNA transcription into mRNA by inhibiting DNA-dependent RNA polymerase by binding its beta-subunit.
Neomycin
prevents ribosome assembly by binding to the prokaryotic 30S ribosomal subunit.
Tetracyclines
block the A site on the ribosome, preventing the binding of aminoacyl tRNAs.
Chloramphenicol
blocks the peptidyl transfer step of elongation on the 50S ribosomal subunit in both bacteria and mitochondria
Macrolides
as well as inhibiting ribosomal translocation[8] and other potential mechanisms) bind to the 50s ribosomal subunits, inhibiting peptidyl transfer
fluroquinolones
inhibition of nucleic acid function or synthesis
what has resulted in the resistance to fluroquinolones/
alteration in the target enzyme - DNA gyrase
how do Blactams enter gram negative bacteria?
through porin channels
how are enterobacter largely resistant to cephalosporins?
B lactamases (also may have altered channels through which now cannot pass through)
what has stopped tetracyclines being effective against gynecologic infections
plasmid mediated protein that promoted efflux of drug
B lactamases (penicillinases) do what
destroy the B lactic ring
methicillin binding site responsible for what ?
methicillin resistance in staph aureus
what shape is the B lactic ring/
square
what does clavulanic acid do?
inhibits many B lactamases by binding to the B lactamase - protecting other B lactase from the enzyme
which B lactcams are B lactase resistant?
monobactam and carbapenem nucleus
