7: Chemotherapy Flashcards
insertion
add one or more base pairs
recombination, phage insertion
deletion
loss of one or more base pairs
rearrangement
flip regions of DNA translocation genes on fringes are affected Chonic Myelogenous Leukemia BCR, ABL
Gleevec
silver bullet anticancer drug
specific target which is only found in cancer cell
Hedgehog
controls left/right polarity in people
Ames test
determine if a compound is carcinogenic
fail the ames test, cause cancer
performing Ames test
get salmonella histadine auxotrophic mutant… it has to be supplemented w/ histadine (the regular doesn’t)
- can’t make histadine bc of single nucleotide polymorphism
- look for change BACK to ability to make histadine (due to a mutation caused by the compound)
What compounds Ames test is good at finding
compounds that covalently change DNA or modify specificity the DN A polymerae
What compounds Ames test is NOT good at finding
identifying carcinogens that are toxic AFTER modification
antibiotics
kill bacteria
antivirals
INHIBIT (not kill) viruses
antiprotozoan, antihelminthic drugs
kill eukaryotic parasites
cancer drugs
gleevec
most go after specific function of th cancer… lots of side effects
Keys to chemotherapy
kill the pathogen, not the host
exploit differences between the two (ribosomes, peptidoglycan/cell walls, chitin(fungus))
penicillin
1928… Fleming
large use starting in 1940
Sulfa Drugs
Domagk
testing antimicrobial properties of synthetic chems
was part of a dye
inhibits steptococcal infections
kirby bauer table
measure zone of clearance DIAMETER compare diameter of resistance of organism to determine clinical effectiveness limited by soluble of compound clinically sensitive clinically intermediate clinically resistant
smaller diameter kirby bauer…
need higher conc of chemical to kill bacteria
can you deliver that conc of chemical to target in body? determine sensitivity/resistivity this way
don’t kill the host
E Test (Epsilometer)
bacteria on strip not disc
measure number where the zones of clearance intersect
this is the conc of drug that will INHIBIT growth
MIC
MIC
Minimum Inhibitory Concentration
lowest conc of drug that will inhibit bacterial growth
Broth Dilution Test
incubate bact. in different concs of drug in broth
MLC
MLC
minimum lethal concentration
min amount of bact. to kill
broth dilution data
the conc in the well RIGHT BEFORE growth is the MIC
if growth in all wells, completely resistant
if growth in no wells, completely sensitive
limitations of broth dilution, kirby, and E test
the human body
target conc… where is pathogen and how much do we need to add to pill to get the right conc to the right target?
intracellular pathogens
topical vs. internal
some places of body hard to deliver drugs to (blood brain barrier)
side effects of chemotherapy
add lots of antibiotics, kill lots of bacteria, let yeast grow… THRUSH (yeast infection)
C. diff in hispitals
change to digestive tract flora
LPS release–inflamation, endotoxin
LPS release as a side effect of chemotherapy
very inflammatory molecule
released when gram neg bact dies
inflammation over whole body
sepsis… gram neg bact in bloodstream, give antibiotics, kill and then release all the LPS… shock…. you die
bacteriocidal
kill
bacteriostatic
stops growth
let immune system do clean up
gentler
broad vs. narrow spectrum
know exactly what causes something? Use narrow, may have less side effects
broad kills a lot of bacteria, use if we don’t know whats causing disease
psedomonads
subset of gram neg
very hard to kill
immunocompromised people
resistant to many antibiotics
penicillin
inhibits peptidoglycan synthesis
