Part 1: Antimicrobial Agents Flashcards
1
Q
what is the overall goal of antimicrobial therapies?
A
to kill infectious organisms while sparing beneficial or symbiotic micro-organisms and host tissues
2
Q
most infectious microorganisms are ____ (prokaryotic or eukaryotes)
A
prokaryotic
3
Q
what is the benefit of most microorganisms having different cellular features and processes than our own cells?
A
makes it easier to target just the infection when taking an antimicrobial
4
Q
why can cell wall inhibitors like penicillin be given at such high doses?
A
our host cells do not have cell walls
5
Q
give an example of a metabolic pathway that drugs can target more effectively in microorganisms than in our host cells
A
folic acid pathway
6
Q
t/f at high doses, antimicrobials that target folate metabolism may also interfere with host cell metabolism, but the dose needs to be very high
A
true
7
Q
which microorganisms are the toughest to target?
A
viruses
8
Q
why are viruses so challenging to target?
A
they enter host cells and use the host cell components to replicate
9
Q
briefly describe the process of a virus entering a host cell, replicating and releasing
A
- virus attaches and enters host cell in endosome
- genetic material released into cytoplasm where it is replicated
- components of new viral particles are packed and released into circulation to infect new host cells
10
Q
t/f some viruses do enough damage to a host cell during their infection/replication process that the host cell dies
A
t
11
Q
aside from the virus, what else can cause a lot of tissue damage during viral infection?
A
host immune system response
12
Q
what activates the immune system in a viral infection?
A
host cells displaying the viral antigen
13
Q
the few antiviral drugs that exist often target what processes?
A
entry into host, uncoating, viral genome replication and release of new viral particles
14
Q
instead of cholesterol (our cells), what is found in the cell membrane of fungal cells?
A
ergosterol
15
Q
what are the primary targets of anti fungal drugs?
A
fungal membrane integrity and ergosterol synthesis (cause fungal cells to rupture)
16
Q
what are unique fungal specific transporter and enzyme used in the making of fungal proteins?
A
transporter: cytosine permease
enzyme: cytosine deaminase
17
Q
what is the benefit of the cytosine permease transporter being found at high levels in fungal cells?
A
allows for drug accumulation in the fungal cell
18
Q
the cytosine deaminase enzyme activates pro-drug into a ___ agents
A
cytotoxic
19
Q
the most common antimicrobial therapies are against ____ type infections
A
bacteria
20
Q
a major target for bacterial drug targeting is the ___ cell wall
A
peptidoglycan
21
Q
cells with an outer membrane around their cell wall are classed as Gram ___
A
negative
22
Q
gram negative have a ____ (thinner/thicker) peptidoglycan cell wall?
A
thinner
23
Q
what colour is gram + stain?
A
purple
24
Q
what colour is gram - stain?
A
red/pink
25
t/f the outer membrane of gram - cells makes drug permeation difficult
true
26
bacteria have __ and ___ ribosomal subunits and our cells have __ and ___ subunits
30s & 50s; 40s & 60s
27
several antibiotics bind specifically to different sites on bacterial ribosomes to disrupt ___
bacterial protein synthesis
28
what is the shape of bacterial DNA?
single circular strand
29
t/f bacterial DNA replication requires transcription machinery that is different from host
true
30
explain bacteriostatic and bactericidal drug treatment
1. bacteriostatic: stalls bacterial growth and gives immune system a chance to catch up to clear the infection
2. bactericidal: drug kills the bacteria and there is less reliance on the host immune system
31
antibacterial drugs are also called ___
antibiotics
32
when are bactericidal antibiotics preferred?
when the host immune system is impaired
33
give 4 examples of why an antimicrobial treatment may fail
1. poor patient adherence
2. poor pharmacokinetics
3. dose too low
4. microbe is not sensitive to the drug given
34
how might poor patient adherence lead to antimicrobial treatment failure?
if not taken as directed, the infection may not be adequately controlled and worsening or resurgence of infection is likely
35
how might poor pharmacokinetics impact treatment failure?
may not get to the site of action adequately enough
36
the minimum concentration required to inhibit or kill bacteria is called the ____
MIC
37
t/f in most cases, doses of antimicrobials are given to ensure the concentration at the site of infection exceeds the MIC
t
38
if increasing the concentration of drug increases the rate of antibiotic effect, the drug is said to be ___
concentration dependent antibiotic
39
t/f if the antibiotic is concentration dependent, in some cases, it may be beneficial to give larger doses to clear the infection more quickly
t
40
explain time-dependent antibiotics
work for a set period of time and increasing the concentration past about 3x will not increase the antibiotic effect
41
for which type of antibiotic is it especially important to take at the time indicated by the prescriber?
time-dependent
42
give an example of an antibiotic class that has post-antibiotic effects
ahminoglycosides
43
how do ahminoglycosides exhibit their post-antibiotic effects?
large doses are given to kill many bacteria quickly, but after the drug enters the bacteria it persists, so those bacteria that aren't immediately killed aren't able to keep replicating
44
t/f even after the systemic levels or amino glycoside dry, there is still an antibacterial effect remaining for some time
true
45
the post-antibiotic effect of ahminoglycosides is advantageous to the ___ of dosing. why is this beneficial?
frequency; they have significant ADRs, so less frequent dosing is advantageous
46
t/f sometimes more than one antimicrobial agent may be needed
t
47
when administering 2 antimicrobial agents, it is important to consider of they are ___ or ____ wrt to each other
antagonistic or synergistic
48
what is mutual antagonism?
both drugs X and Y results in worse outcome than having either drug on their own
49
what is indifference?
the two drugs don't intereact and they exhibit their antibiotic effects independently of each other
50
if there is question surrounding whether an infectious organism will be sensitive to a particular drug, what testing should be performed in advance?
sensitivity testing to determine the best therapeutic choice
51
how can microbes be inherently resistant to a drug?
if the drug is targeting something the microbe doesn't have (ex: trying to use antibiotic to cure the rhinovirus)
52
genes for antimicrobial resistance can be genetically passed by ___ or ____
gene transfer; or bacterial replication
53
t/f most health authorities and general hospitals keep publications of local resistance patterns to help guide treatment decisions when sensitivity testing is not possible or practical
t
54
what are the 6 most common pathways of microbial resistance to drugs?
1. alteration of target sites
2. enzymatic inactivation
3. overproduction of target sites
4. decrease in cell permeability
5. efflux pumps
6. alternate growth patterns
55
what are the 3 main features of microbial drug resistance?
1. drug doesn't bond to target anymore
2. drug doesn't accumulate in the cell to a high enough concentration (inactivated, cant get in, or is pumped out)
3. microbe alters its biochemical pathways
56
vancomycin is subject to what type of microbial resistance?
alteration of target sites
57
beta-lactams are subject to what type of microbial resistance?
enzymatic inactivation
58
sulfanomides are subject to what type of microbial resistance?
overproduction of target sites
59
fluoroquinolones are subject to what type of microbial resistance?
decrease in cell permeability
60
tetracylines are subject to what type of microbial resistance patterns?
efflux pumps
61
should prophylaxis with antibiotics be the norm for healthy patients?
no! microbial resistance risk! only for those with a compromised immune system
62
most antimicrobial prescribing for mild cases is based off of clinical presentation of symptoms and an educated guess called ____ therapy
empiric
63
what antibiotics are typically the first choice for infection (provided no allergy)?
penicillins
64
penicillins have good activity against Gram ___
+
65
what is a situation where sensitivity testing would be needed?
serious infection with suspected resistance
66
which has a lower chance of treatment failure, targeted or empiric antibiotic treatment?
targeted
67
why may sensitivity testing be inconvenient?
takes time, infection can worsen in that time
68
If a patient presents with a serious infection, what is the general course of action for antibiotics?
start empiric until test results show what to target
69
most empiric therapy antibiotics have what spectrum of activity?
broad
70
what are extended spectrum antibiotics?
in between narrow and broad, effective against some G+ and some G-
71
t/f antibiotics are the most commonly used Rx drugs, s their effects are more commoly reported
t
72
ADRs of antimicrobials is typically not caused by the antimicrobial MOA of the drug, but rather caused by ___
off target effects of the drug or secondary effects of disrupting the balance of microorganisms in the body
73
what are some of the more common ADRs of antimicrobials?
effects on normal flora (diarrhea, opportunistic infections)
contraceptive failure
74
what are some of the more rare ADRs of antimicrobial therapy?
1. antibiotic teratology
2. antibiotic induced mania
3. long QT interval syndrome
4. antibiotic induced agranulocytosis
75
what are two opportunistic infections that can happen if too much good bacteria are killed by antibiotic?
1. c. diff (colon, toxins, cell death in intestine, diarrhea)
2. candidiasis (oral thrush, vaginal yeast infection)
76
t/f sometimes the secondary infections after antimicrobial treatment can resolve on their own, but sometimes they also need to be treated
t
77
what types of antibiotic are most common for secondary opportunistic infections?
broad spectrum (amoxicillin, 3rd gen cephalosporins, clindamycin)
78
t/f there is a lot of debate over if antimicrobials can cause contraceptive failure leading to pregnancy
true
79
by what mechanism might antimicrobials reduce efficacy of birth control?
can induce CYP, causing low levels of circulating hormones, which can result in failure and pregnancy
80
the hormones in birth control pills are metabolized by what enzymes?
CYP
81
how may Rifampin lead to contraceptive failure?
induce CYP
82
t/f other than Rifampin, no other antibiotics have been shown to induce CYP, but the old-wives tale about antibiotics and contraceptive failure still persists
t
83
what are 3 proposed mechanisms of antibiotics leading to contraceptive failure?
1. CYP induction
2. reduced GI absorption of BC due to diarrhea
3. reduction in enterohepatic circulation by causing reduced oral F of BC
84
what is enterohepatic circulation?
process by which bacteria in the GI tract increase the F of drugs
85
MO in the GI tract use ___ as a nutrient source
hormone metabolites
86
explain the process of enterohepatic circulation with estrogen in BC pills as an example substrate
1. estrogen orally = subject to 1st pass metabolism in the liver
2. sulfate metabolite is produced from liver metabolism
3. metabolite goes into GI tract where bacteria take the sulfate and spit the estrogen back into the GI tract
4. recycled estrogen can be reabsorbed and some to systemic and some remetabolized
87
t/f there is no concrete evidence that antibiotics except rifampin cause contraceptive failure, but it is best practice to warn patients
true
88
what is the formula for how long extra protection against pregnancy should be used after taking an antibiotic?
t 1/2 of the antibiotic x 5
89
# True / False
Limit the duration of prophylaxis to be as short as the time in which maximum contamination is expected
True
90
# True / False
Consider narrow-spectrum antibiotics targeted at the most important infectious organisms
True
91
# True / False
The prophylactic dose is generally lower than when the same drug is used for acute treatment
True
92
# True / False
In routine prophylaxis, there is a need to preserve the native biome as much as possible
True
93
Patient A and B took the same antiTB drugs rifampicin and isoniazid as maintenance treatment for 6 monts with good compliance.
Upon completion, A still showed TB lesions, while B has clear results. This is an example of
**
a. between-patient variability
b. development of resistance
c. interoccasion variabilit
d. within patient variability**
Between patient variability
94
The most valualbe and time-tested method for immediate identification of bacteria is examination of the infected secretion of body fluid using
**
a. all of the choices
b. complete blood count
c. culture and sensitivity
d. gram staining
e. c-reactive protein (CRP)**
Gram staining
95
# True about definitive therapy
a. pathogen has been identified and susceptibility results are already known
b. combination therapy is preferred
c. important in preventing resistance to monotherapy
d. all of the choices
Definitive therapy: pathogen has been identified and susceptibility results are already known
96
The most common recommended prophylactic antimicrobial for surgery
Cefazolin
97
# Which if the following statements is correct?
* to minimize resistance, drugs should be discontinued
* an ineffective drug may be given in combination to enhance effect
* combination therapy should have similar mechanism of action
* drugs with similar toxicity should be avoided
98
# Which of the following contributes to drug resistance?
* increase activation of prodrugs
* retains target enzyme
* decrease DNA repair
* decrease drug accumulation
99
# True / False
Hydrophilic antibiotics are primarily cleared by the liver
False
100
# True / False
Levofloxacin is a good antibiotic for urinary tract infections
True
101
Drugs that posses concentration dependent killing with good or prolonged post antibiotic effect
aminoglycosides
102
# True / False
For eye infections, standard therapy is via oral route
False
*standard therapy is direct instillation of antibiotics into the ocular cavity*
103
# Not true about drugs with timed-dependent killing
* with prolonged post antibiotic effect
* drugs are given several times a day
* drug concentration persists above MIC for longer duration
* example is ampicillin
with prolonged post antibiotic effect
104
# **
What type of drug resistance is present in enterococcus which after developing vancomycin resistance, develops vancomycin-requiring strains
Incorporation of the drug
105
The infection is controlled but not completely eradicated by the initial round of antimicrobial treatment. Therapy is continued at a lower dose
Suppressive therapy
