L21 + 22 - Anti-microbials

Question 1

What are the different antibiotic drug classes?

Answer 1

• beta-lactams: target cell wall synthesis
• antiseptics: target the outside of bacteria
• aminoglycosides: target ribosomes
• imidazoles: target chromosomal DNA

Question 2

What is an antiseptic drug?

Answer 2

chlorhexidine

• target site: bind to -ve charged phosphate on lipid membrane
• specificity: broad-spectrum against all bacteria but also binds to our cells

Question 3

What is a B-lactam drug?

Answer 3

penicillin-G

• target site: binds to transpeptidase PBP that links peptidoglycan sugars peptidoglycan wall synthesis
• specificity: gram +ve bacteria

Question 4

What is an aminoglycoside drug?

Answer 4

Gentamicin

• target site: irreversibly binds to the 30S subunit of bacterial ribosome
  specificity: broad spectrum, not anaerobes as drug transporter channel requires oxygen

Question 5

What is an imidazole drug?

Answer 5

Metronidazole

• target site: reduced to generative reactive oxygen species that cause breaks in the genome and prevent replication
• specificity: anaerobes as nitroreduction needed for entry into cells, bacteria and protozoa

Question 6

What are the different antiviral drug classes?

Answer 6

• M2 and NA inhibitors
• reverse transcriptase inhibtors
• DNA polymerase inhibitors

Question 7

What is an example of a M2 & NA inhibitor?

Answer 7

Oseltamavir

• target site: Neuraminadase inhibitor (NA) prevents cleavage of sialic acid & release of virus
• specificity: influenza A & B strains

Question 8

What is an example of a reverse transcriptase inhibitor?

Answer 8

Tenofovir

• target site: dATP analog that incorporates into viral DNA causing chain termination = prevents viral replication
• specificity: HIV and HBV reverse transcriptase

Question 9

What is an example of DNA polymerase inhibitor?

Answer 9

Acyclovir:

• target site: dGTP analog incorporated into viral DNA causing chain termination = prevents viral replication
• specificity: HSV

Question 10

What antifungal drug classes are there?

Answer 10

cholesterol inhibitors:

• polyenes
• azoles
• allyamines

Question 11

What is an example of a polyene antifungal?

Answer 11

Nystatin

• target site: bind ergosterol = form pores in membrane
• specificity: oral and skin candidosis

Question 12

What is an example of a azole antifungal?

Answer 12

Fluconazole:

• target site: inihibits 14-alpha demethylase in ergosterol production pathway (lanosterol -> ergosterol)
• specificity: any candidosis

Question 13

What is an example of an allyamine antifungal?

Answer 13

Terbinafine

• target site: inhibits squalene epoxidase
• specificity: athletes foot + ringworm (also targets host cells because squalene also in host cholesterol production)

Question 14

What are the antiprotozoal drug targets?

Answer 14

• imidazoles (transported and reduced the same as in bacteria)
• aminoquinolines

Question 15

What is an example of an aminoquiline antiprotozoal?

Answer 15

Chloroquine

• target site: inhibits heme polymerase activity = free heme which disrupts membrane function + toxic to parasite
• specificity: non-specific but targets infected RBC more than non-infected (toxic)

Question 16

What mechanisms of drug resistance have microbes acquired against antibiotics?

Answer 16

• B-lactams: B-lactamases, altered PBPs (transpeptidases) in S. aureus
• aminoglycoside: enzyme modification, ineffective transprot due to transporter mutation, altered 30S binding site in E.coli, M. tb, Pseudomonas, Enterobacter
• NA & M2 inhibitors: altered NA, complete change of NA from another influenza strain
• RT inhibitors: altered reverse transcriptase in HIV
• aminoquinolines: new efflux pump to remove drug in plasmodium strains