Principle of Chemo Flashcards
Uniqueness of chemotherapy
selective toxicity
selects for resistant strains
hypersensitivity is a problem
lowers the microorangism load so host defense can rid the body of foreign organisms
Pharmacodynamics: types of inhibition
CWS, DNA replication, folic acid production, transcription and translation
6 General mechanisms of resistance
- pathogen fails to absorb drug
- pathogen inactivates drug
- pathogen pumps drug out
- drug target is modified
- increased production of target molecules
- altered metabolic pathway
Vertical transfer
from mother to daughter cells
Tranduction
bacteriophage incorporates DNA; usually lyses cell
Transformation
free DNA is taken up by bacteria
Conjugation
sex pilli passes genes
These have strains that are resistant to all known drugs
entercocci, pseudomonas, enterbacters
Narrow spectrum drug for Mycobacteria
Isoniazid
Extended spectrum drug for listeria and gram (-) (e. coli, Hib, proteus, salmonella)
Ampicillin
Ampicillin is DOC for
Listeria
Broad spectrum drug for chlamydia, mycoplasma, rickettsiae, spirochetes, other gram (-)
Tetracyclines
Larger the zone of clearance
larger sensitivity to that abx
Bactericidal
cell death (CWSI)
Bacteriostatic
growth inhibition
Organism dependent bactericidal
Chloramphenicol (pneumococci, meningococci, and haemophilus influenza)
MOST important to maintain blood levels with
static drugs
Never use in immunocompromised
bacteriostatic drugs
MBC
minimum bactericidal concentration
MIC
minimum inhibitory concentration
Concentration dependent killing
rate and extent of killing dependent on drug concentration (Aminoglycosides, quinolones)
Time dependent killing
killing is not increased with increasing concentrations above MBC (beta-lactams, vancomycin)
PAE
persistent suppression of microbial growth that occurs after levels of abx have fallen below MIC; long PAE = usually 1 dose/day; (Aminoglycosides and fluroquinolones)
Major benefit of PAE
reduced dosing intervals, which reduces adverse side effects
Synergism
when the inhibitory or killing effects of two or more antimicrobials used together are significantly greater than expected from their individual uses (PCN + aminoglycosides)
Mechanisms of synergism
- block sequential steps (TMP-SMX)
- inhibit enzymatic inactivation (beta-lactamase inhibitors)
- enhance uptake (PCN increase uptake of aminoglycosides; amphotericin B increases uptake of flucytosine by fungi)
Enterococcal endocarditis
PCN + aminoglycoside
Pseudomonas infection
PCN (ticarcillin, piperacillin) + aminoglycoside
H. pylori
Bismuth + metronidazole + tetracycline
Listeria
ampicillin + aminoglycoside
Goals of treating with multiple anitbiotics
decreasing toxicity, broad spectrum coverage
Antagonism
inhibition of cidal activity by static agents (meningitis: PCN + chloramphenicol)
Induction of enzymatic inactivation (gram - bacilli: enterobacter, pseudomonas, serratia, citrobacter have inducible beta-lactamases)
Ex. of antagonism
Linezolid + gentamycin
Most likely to cause superinfection
broad-spectrum (clindamycin)
Intestinal candidiasis tx
continue abx; and treat w/ oral nystatin or amphotericin B
Staph enterocolitis
discontinue abx, treat with ORAL vancomycin
Pseudomembranous colitis
discontinue abx, treat with ORAL vancomycin (metronidazole is 2nd line)
Prophylaxis for HSV
acyclovir
prophylaxis for GBS infections
ampicillin or pen G
Haemophilus influenza prophylaxis
rifampin
prophylaxis for malaria
chloroquine
Meningococal prophylaxis
rifampin
Pertussis prophylaxis
erythromycin
Pneumococcemia prophylaxis
pen G
TB prophylaxis
isoniazid
UTI prophylaxis
bactrim (trimethoprim-sulfamethoxazole)
Surgery prophylaxis
cefazolin
