Pathophysiology for Virus/Bacteria/Fungi

Question 1

Targets dictated by…

Answer 1

• Pathogens, not hosts
• Harder to specifically target the closer the organisms are related
• Bigger genomes can mean more drugs

Question 2

Targets + Virus

Answer 2

• Simple genomes, 5-50 genes
• Generally acquire resistance through target gene mutations during lower fidelity gene replication
• Huge numbers of virus particles made, even unlikely mutations occur
• No efflux role (no ATP and only present in host cell)
• Very different from humans for selectivity but small genomes only give a few targets

Question 3

Targets + Bacteria/Fungi

Answer 3

• Complex genomes with thousands of genes and lots of potential resistance mechanisms
• Bacteria: mostly different from people with larger genome, lots of resistance mechanisms
• Fungi: similar to humans, few unique targets, resistance mechanisms to most agents, but rare to infect

Resistance acquired by…

• Modification of target genes and control elements and amplification of target genes
• Activation of efflux pumps, lowered uptake, lowered activation of prodrugs
• Activation of antibiotic metabolism/inactivation

Question 4

Treating Virus W/O Antivirals

Answer 4

• Supportive therapy: rest, fluids, OTC painkillers

- Vaccination: not always very effective due to mutations or lack of development

Question 5

Types of Antivirals

Answer 5

1. Host directed immune therapies (will increase in importance as drug resistance continues)
2. Antiviral drugs

-Need a unique non-eukaryotic target in the viral genome

Question 6

Antiviral Downsides

Answer 6

• Few good targets available
• Viruses have massive numbers of replications that can lead to resistance (multidrug therapy can help reduce this)
• Targets usually species specific and no real “broad spectrum” compounds available

Question 7

Unique Mycobacteria Targets

Answer 7

• Thick, waxy cell wall
• DNA synthesis
• ATP synthase

Question 8

Shared Mycobacteria Targets

Answer 8

• Peptidoglycan - broadly B lactam resistant
• DNA dependent RNA polymerase
• Protein synthesis

Question 9

Myocbacterial Resistance

Answer 9

• No plasmid mediated resistance transfer (good!)
• Lots of intrinsic resistance (bad!)
• Ready developed acquired resistance due to prolonged therapy if not effective multidrug regimen

Question 10

Fungal Drug Targets

Answer 10

• Unique outer cell wall
• Unique sterols in plasma membrane
• DNA Synthesis (5 fluorocutosine)

Question 11

Fungal Resistance

Answer 11

• Many species have intrinsic resistance to some/many classes of drugs
• Acquired resistance during therapy also occurs from mutations