B3.010 Introduction to Antimicrobial Chemotherapy

Question 1

what are the 4 qualities a drug must have to be effective?

Answer 1

1. get where its needed
2. in an active form
3. in a sufficient quantity
4. for a sufficient time

Question 2

absorption

Answer 2

defines routes of administration

special considerations given to speed, reliability, and compliance

Question 3

what are some important things to consider when examining drug distribution?

Answer 3

reliability
important of blood and tissue levels in therapeutic and toxic effects
entry into mammalian cells

Question 4

what are some sites of exclusion of drug distribution?

Answer 4

blood/brain barrier
ocular fluid
synovial fluid
pleural fluid
cysts (physical barrier)
necrotic tissue (physical barrier)

Question 5

why is metabolism important?

Answer 5

host metabolism is not important for many anti-microbials, but required for some antivirals
metabolism by pathogen may be a key determinant of activity and specificity

Question 6

what % of chemotherapeutic agents are toxic?

Answer 6

all of them

100%

Question 7

what is the goal of chemo?

Answer 7

selective toxicity targeting a pathogen rather than the host

Question 8

how is selective toxicity achieved?

Answer 8

1. unique target present in pathogen and absent in host
2. target structurally different in pathogen than in host
3. target more essential in pathogen than in host

Question 9

what are some of the targets for selective toxicity?

Answer 9

cell wall synthesis (good bc mammalian cells don't have cell walls)
membrane integrity
protein synthesis 
nucleic acid synthesis
nucleic acid integrity
cytoskeleton integrity
lipid synthesis
energy production

Question 10

when targets are not unique to pathogen, what may enhance selective toxicity?

Answer 10

fundamental differences between species and cell types

Question 11

what are the major classes of anti-bacterial drugs

Answer 11

A. cell wall synthesis inhibitors
B. membrane affectors
C. Inhibitors of protein synthesis
D. Folate inhibitors
E. DNA gyrase inhibitors
F. Urinary tract antiseptics
G. Anti- mycobacterial drugs

Question 12

what are the sub classes of cell wall synthesis inhibitors?

Answer 12

1. penicillins
2. cephalosporins
3. other B-lactams
4. other inhibitors

Question 13

what are the sub classes of inhibitors of protein synthesis?

Answer 13

1. tetracyclides
2. macrolides
3. aminoglycosides
4. other inhibitors

Question 14

what are the sub classes of folate inhibitors?

Answer 14

1. sulfonamides

2. reductase inhibitors

Question 15

what are the sub classes of DNA gyrase inhibitors?

Answer 15

1. fluoroquinolones

Question 16

what are the 5 key features of pharmacodynamics for chemotherapeutic drugs?

Answer 16

1. mechanism of action
2. spectrum of activity
3. static vs cidal
4. development/incidence of resistance
5. role of host defenses

Question 17

what do cyto- or bacterio-static drugs do?

Answer 17

inhibit growth and proliferation

Question 18

what do cyto- or bacterio-cidal drugs do?

Answer 18

kill pathogens

Question 19

are static or cidal drugs prefereed in immunocompromised patients?

Answer 19

bacteriocidal

Question 20

what happens when you combine bacteriostatic drugs?

Answer 20

can have a bacteriocidal effect

synergy

Question 21

how does the role of host defenses combine with chemo?

Answer 21

chemotherapy seldom produces a cure directly
host immune function usually provides the final cure
in immunocompromised patients, bactericidal agents usually are more effective

Question 22

what is time dependent killing?

Answer 22

used by pens, cephs, vancomycin
time above MBC relates to efficacy
MBC = minimum bactericidal concentration

Question 23

what is concentration dependent killing?

Answer 23

used by aminoglycosides, fluoroquinolones
peak serum concentration relates to the extent of killing
higher peak values result in increased efficacy and decreased development of resistance

Question 24

what are some things that would have been impossible without antimicrobial drugs?

Answer 24

joint replacement
organ transplant
cancer chemotherapy
high survival rates for premature infants
ICUS

Question 25

describe how resistance develops

Answer 25

only pathogens sensitive to a given drug or combination of drugs will be affected resistant pathogens will then enjoy a selective advantage for growth and proliferation selection for resistance is rapid and reversibility is slow/non-existent

Question 26

what facilitated the emergence of resistance?

Answer 26

misuse, overuse overuse of broad spectrum drugs global society decline in antimicrobial drug development

Question 27

antibiotic stewardship

Answer 27

treat infections only when benefit outweighs individual and global risks bronchitis, sinusitis, otitis media overall show little benefit from antibacterial therapy

Question 28

what are general mechanisms for resistance?

Answer 28

1. pathogen does not absorb drug 2. pathogen pumps drug out 3. pathogen metabolism inactivates drug 4. modified target in pathogen not affected by drug 5. increased production of target molecules 6. development of altered metabolic pathways to bypass target

Question 29

what is non-genetic (temporary) resistance?

Answer 29

pathogen may be metabolically inactive, or dormant

Question 30

what are 2 forms of genetic (permanent) resistance?

Answer 30

chromosomal -based on mutation in gene coding for target -lose effect of drug but maintain normal function -pass on to progeny extrachromosomal -based on addition of plasmid to pathogen -plasmids may carry multiple genes providing multiple drug resistance -plasmids may be passed on to other cells without proliferation

Question 31

how can you minimize the emergence of resistance?

Answer 31

only use chemotherapeutic agents when they are clearly indicated use narrow spectrum drug known to be effective against the pathogen which is present use an effective dose of the chemotherapeutic agent consider the patient's phenotype/genotype in establishing dosing regimen ensure that the duration of chemo is adequate use older drugs when possible use multiple drugs in combination chemo when the pathogen is noted to develop resistance to an individual drug rapidly

Question 32

what is a superinfection?

Answer 32

appearance of a new, often more severe, infection as a result of primary chemotherapy alter normal flora and see overgrowth of other microorganisms often GI

Question 33

how can you distinguish a superinfection from direct irritation by the drug?

Answer 33

time course | superinfections take longer to develop and then occur all of a sudden

Question 34

what are the 3 major glasses of GI superinfections?

Answer 34

1. candidiasis - fungal - most common - continue antibacterial, add antifungal 2. staphylococcal enterocolitis - life threatening - discontinue anti-bac - administer anti staph penicillin or vancomycin 3. pseudomembranous colitis - life threatening - c.diff - discontinue antibacterial - administer metronidazole or vancomycin

Question 35

what are 3 primary adverse effects of chemotherapy?

Answer 35

1. toxicity to host - dose related - often related to mechanism of action 2. hypersensitivity - immune mediated toxicity - not related to dose 3. idiosyncratic responses - may be genetically determined - may reflect altered pharmacokinetics

Question 36

indications for combination chemotherapy

Answer 36

1. for enhanced effect (synergism) 2. to allow for lower doses or individual drugs to minimize toxicity for the patient 3. to delay development of resistance 4. for the treatment of mixed infections 5. to initiate therapy in life threatening situations when the pathogen is not known

Question 37

indications for chemoprophylaxis

Answer 37

1. to protect healthy individuals following exposure to specific pathogens 2. to minimize active, symptomatic episodes of chronic infections 3. to prevent post surgical infections 4. to prevent bacterial endocarditis

Question 38

drug selection in chemotherapy in 4 steps

Answer 38

1. can the drug affect the pathogen? 2. are the pharmacokinetics of the drug appropriate? 3. is the drug appropriate for the patient? 4. is the drug ideal?