Antimicrobial Chemotherapy Flashcards
1
Q
what are chemotherapeutic agents?
A
chemical agents used to treat disease
2
Q
who do chemotherapeutic agents do? (2)
A
- detstroy pathogenic microbes or
2. inhibit their growth within a host
3
Q
what kind are most chemotherapeutic agents?
A
antibiotics
4
Q
describe antibiotics
A
microbial products or their derivatives that kill susceptible microbes or inhibit their growth
5
Q
what kind of disease was there lots of in the 1500’s?
A
venereal
6
Q
what were the only 2 treatment options for venereal and other diseases in the 1500’s/early medicine?
A
- mercury agents or paste
2. arsenic
7
Q
describe the link between STDs and malaria in early medicine
A
patients with STDs AND malaria had a fever that killed that the siphylis, so doctors tried heat chambers to recreate or straight injected patients with malaria
8
Q
who accidentally discovered penicillin in 1928? how?
A
Alexander Fleming; observed penicillin activity on a contaminated plate
9
Q
did Fleming think penicillin could go further? who helped?
A
he did not; Florey, Chain, and Heatly demonstrated effectiveness
10
Q
what is selective toxicity?
A
the ability of a drug to kill or inhibit pathogen while damaging the host as little as possible; a general characteristic of antimicrobial drugs
11
Q
what is therapeutic dose?
A
drug level required for clinical treatment; a general characteristic of antimicrobial drugs
12
Q
what is toxic dose?
A
the drug level at which the drug becomes too toxic for the patient and produces side effects
13
Q
what is the therapeutic index?
A
the ratio of toxic dose to therapeutic dose
14
Q
do you want a low or high therapeutic index? why?
A
you want a higher therapeutic index because it will have better/higher selective toxicity
15
Q
what are side effects?
A
undesirable effects of drugs on host cells
16
Q
what are narrow-spectrum drugs?
A
attack only a few different pathogens; a general characteristic of antimicrobial drugs
17
Q
what are broad spectrum drugs?
A
attack many different kinds of bacteria; a general characteristic of antimicrobial drugs
18
Q
what is a cidal agent?
A
kills the target pathogen
19
Q
what is a static agent?
A
reversibly inhibits growth of microbes
20
Q
what 3 things have an effect of the effectiveness of antimicrobial drugs?
A
- concentration
- microbe
- host
21
Q
how is antimicrobial drug effectiveness expressed? (2 ways)
A
- MIC: minimal inhibitory concentration: the lowest concentration of the drug that PREVENTS GROWTH of the pathogen
- MLC: minimal lethal concentration: the lowest concentration of a drug that KILLS PATHOGENS
22
Q
what are the 4 main modes of action of antimicrobial drugs?
A
- inhibitors of cell wall synthetis
- protein synthesis inhibitors
- metabolic antagonists
- nucleic acid synthesis inhibition
23
Q
name 3 antibiotic drugs whose mode of action is inhibiton of cell wall synthesis
A
- penicllins
- cephalosporins
- vancomycin
24
Q
what is the most crucial structural feature of penicillins?
A
the B-lactam ring
25
what does the B-lactam ring of penicillins do?
is essential for bioactivity
26
what do many penicillin resistant organisms produce and what does it do?
B-lactamase (also called penicillinase), which hydrolyzes a bond in this the B-lactam ring, limiting efficacy of penicillins
27
describe the specific cell wall synthesis-inhibiting mdoe of action of penicillins
blocks the enzyme that catalyzes transpeptidization, preventing synthesis of complete cell walls leading to lysis of cell
28
what is transpeptidization?
formation of cross-links in peptidoglycan
29
what type of bacteria are the target of penicillins?
growing bacteria that are synthesizing new peptidoglycan
30
what are the 2 types of naturally-occurring penicllins? are they broad or narrow-spectrum?
Penicillin V and G; narrow spectrum
31
why are semisynthetic penicillins broader spectrum than naturally occuring penicillins?
the bulkier side chains make them more difficult for B-lactamase enzymes to degrade
32
is resistance to penicillin a problem? for semisynthetics?
yes, and also for semisynthetics
33
compare the structure and function of cephalosporins to penicillins
structurally and functionally similar to penicillins
34
describe cephalosporins (target range and use)
broa spectrum antibiotics that can be used by most patients allergic to penicllin
35
how many categories of cephalosporins are there based on their spectrum of activity?
4
36
what kind of antibiotic is vancomycin (structureish)
glycopeptide antibiotic
37
describe the cell wall synthesis-inhibiting mode of action of vancomycin
prevents transpeptide from ever binding
38
what is vancomycin important for?
important for treatment of antibiotic-resistant staphylococcal and enterococcal infections
39
what was vancomycin previously considered and why is this a concern now?
was the drug of last resort when nothing else worked, so the rise in RESISTANCE to vancomycin is concerning, especially with the MERSA strains that are now resistant
40
would you expects inhibitors of cell wall synthesis ro work better against gram positive or gram negative bacteria? why?
work better against gram positive because those bacteria have only one layer of peptidoglycan that is not protected by an outer membrane like gram negative bacteria's 2 layers of peptidoglycan are
41
do eukaryotic cells have peptidoglycan? what does this mean about the selective toxicity of cell wall inhibitor anytbiotics?
no; pretty high selective toxicity because can target bacteria without targeting us
42
name 3 antibiotics whose mode of action is protein synthesis inhibition
1. aminoglycosides
2. tetracyclines
3. macrolides
43
where do protein synthesis-inhibiting antibiotics bind? how can they find/do this?
specifically to the bacterial ribosome, can differentiate due to the different ribosome densities between bacterial and eukaryotic ribosomes
44
list the 4 different steps in protein synthesis that are targets of protein synthesis-inhibiting antibiotics
1. amicoacetyl-tRNA binding
2. peptide bond formation
3. mRNA reading!
3. translocation
45
describe the specific protein synthesis-inhibiting mode of action of aminoglycosides
bind to 30S ribosomal subunit and interfere with protein synthesis by DIRECTLY inhibiting the process and by causing MISREADING of the mRNA
46
what kind of target spectrum are aminoglycoside antibiotics?
broad spectrum
47
describe the target spectrum of tetracycline antibiotics
broad spectrums
48
/are tetracyclines bactericidal or bacteriostatic?
bacteriostatic
49
describe the specific protein synthesis-inhibiting mode of action of tetracyclines
target the 30S subunit (like aminoglycosides) and slow down protein synthesis (static) and cause SOME misreading but not as much as aminoglycosides
50
give an example of a macrolide
erythromycin
51
describe the macrolide erythromycin (spectrum range and static or cidal)
broad spectrum, bacteriostatic
52
describe the specific protein synthesis-inhibiting mode of action of the macrolide erythromycin
binds to 50S!! subunit to inhibit bacterial protein elongation
53
when are macrolides used?
for patients who are allergic to penicillin
54
describe metabolic antagonists?
1. act as antimetabolites
| 2. are structural analogs
55
how do metabolic antagonists act as antimetabolites?
antagonize or block functioning of metabolic pathways by competetively inhibiting the use of metabolites by key enzymes
56
how are metabolic antagonists structural analogs?
they are molecules that are structurally similar to, and compete with, naturally occurring metabolic intermediates to block normal cellular metabolism
57
list the 2 antimicrobials (and specify which one is an antibiotic) whose mode of action is metabolic antagonism
1. sulfa drugs or sulfonamides
| 2. trimethroprim
58
describe the structural analog nature of sulfa drugs/sulfonamides
structurally related to sulfanilamide, a PABA analog; PABA is used by many pathogens for the synthesis of folic acid
59
how are sulfa drugs slecetively toxic?
due to competitive inhibition of folic acid synthesis enzymes
60
describe trimethoprim
a synthetic antibiotic that also interferes with folic acid production
61
what is the spectrum range of trimethoprim?
broad spectrum antibiotic
62
how is trimethoprim often used?
often combined with sulfa drugs to increase efficacy of treatment
63
what does the combination of sulfa drugs and trimethoprim do?
blocks to 2 steps in the folic acid pathway = more effective
64
what are the most commonly used antibacterial drugs?
nucleic acid synthesis inhibitors
65
describe nucleic acid synthesis inhibitors modes of action (2)
1. inhibit DNA polymerase and topoisomerases (floroquinolones)
2. inhibit RNA polymerase (rifamycins)
66
are nucleic acid synthesis inhibitors as selectively toxic as other antibiotics? why or why not?
no, because bacteria and eukaryotes do not differ greatly in the way they synthesize nucleic acids
67
describe the specific nucleic acid-inhibiting mode of action of fluoroquinolones
act by inhibitng bacterial DNA gyrase and topoisomerase II
68
describe the spectrum range of fluoroquinolones
broad spectrum antiobiotics
69
are fluoroquinolones bacteriostatic or bactericidal?
bactericidal
70
what range of infections do flouoroquinolones treat?
a wide variety (duh bc they're broad spectrum)
71
what has antiviral drug development been slow?
because it is difficult to specifically target viral replication
72
what has the success of antiviral drugs been in the past?
mixed
73
what is the fate of a vast majority of viral infections?
cannot be cured
74
what 2 main things do some antiviral drugs do to an illness? give example
1. limit duration (flu)
| 2. limit severity (herpes, HIV)
75
what do the current antiviral drugs in use do?
inhibit virus-specific enzymes and life cycle processes
76
what type of antiviral agent is Tamiflu?
antiviral
77
what is the mode of action of tamiflu?
neuriminidase inhibitor
78
is Tamiflu a cure for influenza? what does it do?
not a cure, but shortens course of illness
79
how many types of anti-HIV drugs are there?
5
80
why are there so many kinds of anti-HIV drugs?
because it is so widespread and mutates so much
81
name the 5 kinds of anti-HIV drugs
1. nucleoside reverse-transcriptase inhibitors (NRTIs)
2. nonnucleoside reverse-transcriptase inhibitors (NNRTIs)
3. protease inhibitors (PIs)
4. integrase inhibitors
5. fusion inhibitors
82
describe how nucleoside reverse-transcriptase inhibitors work
target and interfere with critical steps in viral replication processes
83
describe how nonnucleoside reverse-transcriptase inhibitors work
prevent HIV DNA synthesis by selectively binding to and inhibiting the viral reverse transcriptase enzyme
84
how do protease inhibitors work?
block the activity of the HIV protease needed for the production of all viral proteins
85
how do integrase inhibitors work?
prevent the incorporation of the HIV genome into the host's chromosome
86
how do fusion inhibitors work?
prevent HIV entry into cells
87
how are most HIV drugs given and why?
as cocktail mixes of multiple kinds of drugs to curtail resistance
88
which 2 antimicrobials are most selectively toxic? in order
1. anitbiotics
| 2. antivirals
89
what 2 antimicrobial agents have the lowest therapeutic index and why?
1. antiprotozoans
2. antifungals
bc those cells are similar to eukaryotic cells; hard to target without killing us too
90
why are there fewer effective antifungal agents? (2)
because of the similarity of eukaryotic fungal cells to human and animal cells; most have low therapeutic index and are toxic
91
what type of fungal infection is easier to treat?
superficial mycosis; easier than systemic mycoses
92
what may be used to treat fungal infections?
a combination of drugs
93
give an example of a superficial mycosis
candida
94
what routes of antifungal mediciation is available to treat superficial mycoses? (2)
1. topical
| 2. oral
95
what is the mode of action of antifungal medications to treat superficial mycoses? (2)
1. disrupts membrane permeability and inhibits sterol synthesis
2. disrupts mitotic spindle, may inhibit protein and DNA synthesis
96
describe systemic mycoses
difficult to control and can be fatal
97
list the 3 common drugs used to treat systemic mycoses, the modes of actions of 2, and the use of the third
1. Amphotericin B: binds sterols in membranes
2. 5-flucytosine: disrupts RNA function
3. Fluconazole: low side effects, used prophylactically
98
is the mechanism of action for many anti-protozoan drugs currently known?
not precisely
99
give 3 examples of antiprotozan drugs
1. some antibiotics that inhibit bacterial protein synthesis
2. quinines: anti-malarial, include chloroquine and mefloquine
3. metronidazole: treats Entamoeba infections
100
what are the 3 types of drug resistance?
1. intrinsic
2. acquired
3. presistence (drug-tolerant bacteria)
101
give an example of intrinic drug resistance by bacteria
mycoplasma resistance to B-lactam and other antibiotics because no cell wall
102
describe acquired drug resistance
occurs when there is a change in the genome of a bacteria that converts it from one that is sensitive to an antibiotic to one that is resistant
103
describe drug-tolerant bacteria
lack the mechanisms for antibiotic resistance, just ignore the presence of antibiotics
104
where are drug-tolerant bacteria found?
1. embedded in biofilms
| 2. bacteria growing too slowly to be inhibited
105
what are the 4 mechanisms of drug resistance?
1. modify the target of the antibiotic
2. drug inactivation
3. minimize the concentration of the antibiotic in the cell
4. bypass the biochemical reaction inhibited by the agent or increase the production of the target metabolite
106
what are the 3 methods to overcome drug resistance?
1. give drug in appropriate concentrations to destroy susceptible microbes and most spontaneous mutants
2. give 2 or mroe drugs at the same time
3. use drugs only when absolutely necessary
107
what are 2 possible future solutions to overcome drug resistance?
1. continued development of new drugs
| 2. use of bacteriophages to treat bacterial disease
