Mechanisms of antimicrobial resistance Flashcards
What are viruses?
Infectious, obligate, intracellular parasites
DNA or RNA genome
Hijack host cell machinery for replication
What is prophylaxis?
Preventing disease before the aetiologic agent is acquires by vaccination or giving a drug before infection
What is treatment?
Treating the disease after infection
Why are anti-viral medications so hard to develop?
High specificity is required
Viruses use our machinery, cannot target infected cells specifically
What is used as targets for anti viral drugs?
Enzymes: Substrate analogues e.g. nucleoside analogues
What is acyclovir?
Nucleoside analogue
Best anti-viral agent
How does acyclovir work?
Modified nucleoside incorporated into genome
Lack of 3’ -OH prevents phosphodiester bond formation
How is acyclovir specific?
Only activated inside virus infected cells
Specificity due to phosphorylation of ACV to ACVMP by viruses-encoded thymidine kinase
Higher affinity for viral DNA polymerase that for host cell polymerase
What would comprise an ideal flu drug?
Target a unique and essential gene to function of the virus
Be effective against a range of influenza types and strains
Easy to administer
Few side effects
What are the three classes of drugs against influenza?
Amantadine
Ribavarin
Zanamivir oseltamivir
What are the main feature of amanatdines?
Cyclic amines with bulky cage-like structures
Byproducts of petrol refinement
Active against influenza A virus only
How do amanatdines work?
Block proton channel prevents viral entering the cells
How has resistance to amantdines evolved?
Single point mutation
Little cost to fitness, resistant circus is virulent and transmissible
Most H3N2 viruses are resistance
Mant H5N1 resistant due to overuse in poultry industry
Name the two drugs that were rationally designed against influenza?
Tamiflu and Relenza
How does Tamiflu work?
Neuraminidase inhibitor
Shorten illness
