32- Antimicrobials and Antineoplastics Flashcards
What is the goal “selective toxicity” of antimicrobials and antineoplastics?
provide antimicrobial and antineoplastic (anti-cancer) drug therapy without affecting the host
What are the 3 ways of selectivity to kill harmful cells?
1) Targets unique to only pathogen or cancer cells (genetic or biochemical pathway) but not host
2) Targets in pathogen or cancer cell that are similar but not identical to those in the hosts
3) Targets in pathogen or cancer cells that are shared by the host. These targets are important for pathogens but not so much for the host.
Why is selective toxicity harder for cancer cells?
in order to target cancers, the drug targets pathways common to both cancer and host
What is the therapeutic index equation?
TI = TD50/ED50
What is better, a small or large therapeutic index?
large
What is the MOA of β-lactams?
inhibit the transpeptidase enzymes that catalyze the final cross-linking step in peptidoglycan synthesis
Why are β-lactams essentially nontoxic to humans?
target the peptidoglycan cell wall which is both biochemically unique and essential for the survival of growing bacteria
What is the difference between bacterial and eukaryotic ribosomes?
bacteria use 70S ribosomes made up of 30S and 50S. We use 80S ribosomes made up of 40S and 60S
Since cancer cells contain our own enzymes and structures, how do we target them?
target through variations in cancer cell growth behavior and from increased susceptibility of cancer cells to induction of apoptosis or senescence
Where is the basis for selectivity for antineoplastic drugs?
lies in the drug’s ability to induce apoptosis in cancer cells but not in most normal cells
What is 5-flurouracil (5-FU)?
inhibits DNA synthesis in dividing cells by inhibiting thymidylate synthase
What cells can be damaged by 5-FU therapy?
5-FU is toxic to all dividing human cells causing both therapeutic and adverse effects
What are the therapeutic effects of 5-FU therapy?
toxic for rapidly cycling tumor cells
What are bactericidal drugs?
drugs that kill bacteria
What are bacteriostatic drugs?
drugs that inhibit growth of pathogen without causing death by targeting metabolic pathways necessary for growth but not survival
What determines the effectiveness of bacteriostatic drugs?
depends on an intact host immune system to clear the nongrowing bacteria
Why are tetracyclines and beta lactams antagonists?
tetracycline is a bacteriostatic drug by inhibiting protein synthesis and penicillin is a bactericidal drug that requires cell growth and division to kill cells. no cell growth –> PCN can’t fxn
How can a penicillin-aminoglycoside combination produces a synergistic effect?
inhibition of bacterial cell wall synthesis by penicillin allows increased entry of aminoglycoside
What is the MOA of aminoquinolones?
Aminoquinolones work by inhibiting the polymerization of heme within the erythrocyte
What does aminoquinolones treat?
Malaria
What is the target of ACV?
viral DNA polymerase
What are the 3 polymerase inhibitors?
- Acyclovir (treats HSV and VZV)
- Zidovudine (“AZT”, treats HIV)
- Efavirenz (treats HIV)
What are the 2 neuraminidase inhibitors?
- Zanamivir (treats Influenza A and B)
* Oseltamivir (treats Influenza A and B)
Why do most anticancer drugs not target cancer cells in the G0 phase?
Most antineoplastic drugs target dividing cells
