Principles of chemotherapy II : antimicrobial drugs

Question 1

Selective toxicity for drugs?

Answer 1

-drugs directed against targets that are involved in function of abnormal cell/invading organism but are not required for host function

Question 2

Static (stop replicating) vs cidial (kill) drugs?

Answer 2

Minimum bacterial concentration = lowest concentration that kills 99.9% of bacteria/fungi after 18‑24h in culture
Minimum inhibitory concentration = lowest concentration of antimicrobial or drug that will inhibit the visible growth of bacteria after overnight incubation

• If MBC is within the non-toxic (to the host) range, the drug is baxtericidal/fungicidal
• If MIC (Minimum Inhibitory Concentration) is within the non-toxic range but MBC isn’t, the drug is bacteriostatic/fungistatic

Question 3

What are the 3 potential drug targets for selectively cytotoxic drugs? Which are the most useful and why?

Answer 3

Class 1 pathways : simple reactions that make ATP for class 2 reactions (NOT SELECTIVE) -Simple biochemical reactions may be targeted if there are fundamental differences between pathogens and mammalian cells

Class 2 pathways: Use ATP to make small molecules

Class 3: Convert small class II molecules into macromolecules (SELECTIVE TOXIC ON BACTERIA WITHOUT HARMING MAMMALIAN CELLS AS COMPLEX PATHWAYS VARY)

Question 4

How may bacteria develop resistance to drugs?

Answer 4

1. Mutation of drug target, producing a molecule which functions normally but does not bind the drug
   e.g. mutated DNA-gyrases confer resistance to quinolones
2. Expression of drug-destroying enzymes
   e.g. β-lactamases inactivate penicillins, etc.
3. Development of drug-excluding mechanisms

Question 5

What are the targets for anitmicrobials?

Answer 5

1. DNA synthesis
2. Cell wall formation
3. Protein synthesis