Part 1: Antimicrobial Agents Flashcards
what is the overall goal of antimicrobial therapies?
to kill infectious organisms while sparing beneficial or symbiotic micro-organisms and host tissues
most infectious microorganisms are ____ (prokaryotic or eukaryotes)
prokaryotic
what is the benefit of most microorganisms having different cellular features and processes than our own cells?
makes it easier to target just the infection when taking an antimicrobial
why can cell wall inhibitors like penicillin be given at such high doses?
our host cells do not have cell walls
give an example of a metabolic pathway that drugs can target more effectively in microorganisms than in our host cells
folic acid pathway
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
true
which microorganisms are the toughest to target?
viruses
why are viruses so challenging to target?
they enter host cells and use the host cell components to replicate
briefly describe the process of a virus entering a host cell, replicating and releasing
- 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
t/f some viruses do enough damage to a host cell during their infection/replication process that the host cell dies
t
aside from the virus, what else can cause a lot of tissue damage during viral infection?
host immune system response
what activates the immune system in a viral infection?
host cells displaying the viral antigen
the few antiviral drugs that exist often target what processes?
entry into host, uncoating, viral genome replication and release of new viral particles
instead of cholesterol (our cells), what is found in the cell membrane of fungal cells?
ergosterol
what are the primary targets of anti fungal drugs?
fungal membrane integrity and ergosterol synthesis (cause fungal cells to rupture)
what are unique fungal specific transporter and enzyme used in the making of fungal proteins?
transporter: cytosine permease
enzyme: cytosine deaminase
what is the benefit of the cytosine permease transporter being found at high levels in fungal cells?
allows for drug accumulation in the fungal cell
the cytosine deaminase enzyme activates pro-drug into a ___ agents
cytotoxic
the most common antimicrobial therapies are against ____ type infections
bacteria
a major target for bacterial drug targeting is the ___ cell wall
peptidoglycan
cells with an outer membrane around their cell wall are classed as Gram ___
negative
gram negative have a ____ (thinner/thicker) peptidoglycan cell wall?
thinner
what colour is gram + stain?
purple
what colour is gram - stain?
red/pink
t/f the outer membrane of gram - cells makes drug permeation difficult
true
bacteria have __ and ___ ribosomal subunits and our cells have __ and ___ subunits
30s & 50s; 40s & 60s
several antibiotics bind specifically to different sites on bacterial ribosomes to disrupt ___
bacterial protein synthesis
what is the shape of bacterial DNA?
single circular strand
t/f bacterial DNA replication requires transcription machinery that is different from host
true
explain bacteriostatic and bactericidal drug treatment
- bacteriostatic: stalls bacterial growth and gives immune system a chance to catch up to clear the infection
- bactericidal: drug kills the bacteria and there is less reliance on the host immune system
antibacterial drugs are also called ___
antibiotics
when are bactericidal antibiotics preferred?
when the host immune system is impaired
give 4 examples of why an antimicrobial treatment may fail
- poor patient adherence
- poor pharmacokinetics
- dose too low
- microbe is not sensitive to the drug given
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
how might poor pharmacokinetics impact treatment failure?
may not get to the site of action adequately enough
the minimum concentration required to inhibit or kill bacteria is called the ____
MIC
t/f in most cases, doses of antimicrobials are given to ensure the concentration at the site of infection exceeds the MIC
t
if increasing the concentration of drug increases the rate of antibiotic effect, the drug is said to be ___
concentration dependent antibiotic
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
explain time-dependent antibiotics
work for a set period of time and increasing the concentration past about 3x will not increase the antibiotic effect
for which type of antibiotic is it especially important to take at the time indicated by the prescriber?
time-dependent
give an example of an antibiotic class that has post-antibiotic effects
ahminoglycosides
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
t/f even after the systemic levels or amino glycoside dry, there is still an antibacterial effect remaining for some time
true
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
t/f sometimes more than one antimicrobial agent may be needed
t
when administering 2 antimicrobial agents, it is important to consider of they are ___ or ____ wrt to each other
antagonistic or synergistic
what is mutual antagonism?
both drugs X and Y results in worse outcome than having either drug on their own
what is indifference?
the two drugs don’t intereact and they exhibit their antibiotic effects independently of each other
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
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)
genes for antimicrobial resistance can be genetically passed by ___ or ____
gene transfer; or bacterial replication
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
what are the 6 most common pathways of microbial resistance to drugs?
- alteration of target sites
- enzymatic inactivation
- overproduction of target sites
- decrease in cell permeability
- efflux pumps
- alternate growth patterns
what are the 3 main features of microbial drug resistance?
- drug doesn’t bond to target anymore
- drug doesn’t accumulate in the cell to a high enough concentration (inactivated, cant get in, or is pumped out)
- microbe alters its biochemical pathways
vancomycin is subject to what type of microbial resistance?
alteration of target sites
beta-lactams are subject to what type of microbial resistance?
enzymatic inactivation
sulfanomides are subject to what type of microbial resistance?
overproduction of target sites
fluoroquinolones are subject to what type of microbial resistance?
decrease in cell permeability
tetracylines are subject to what type of microbial resistance patterns?
efflux pumps
should prophylaxis with antibiotics be the norm for healthy patients?
no! microbial resistance risk! only for those with a compromised immune system
most antimicrobial prescribing for mild cases is based off of clinical presentation of symptoms and an educated guess called ____ therapy
empiric
what antibiotics are typically the first choice for infection (provided no allergy)?
penicillins
penicillins have good activity against Gram ___
+
what is a situation where sensitivity testing would be needed?
serious infection with suspected resistance
which has a lower chance of treatment failure, targeted or empiric antibiotic treatment?
targeted
why may sensitivity testing be inconvenient?
takes time, infection can worsen in that time
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
most empiric therapy antibiotics have what spectrum of activity?
broad
what are extended spectrum antibiotics?
in between narrow and broad, effective against some G+ and some G-
t/f antibiotics are the most commonly used Rx drugs, s their effects are more commoly reported
t
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
what are some of the more common ADRs of antimicrobials?
effects on normal flora (diarrhea, opportunistic infections)
contraceptive failure
what are some of the more rare ADRs of antimicrobial therapy?
- antibiotic teratology
- antibiotic induced mania
- long QT interval syndrome
- antibiotic induced agranulocytosis
what are two opportunistic infections that can happen if too much good bacteria are killed by antibiotic?
- c. diff (colon, toxins, cell death in intestine, diarrhea)
- candidiasis (oral thrush, vaginal yeast infection)
t/f sometimes the secondary infections after antimicrobial treatment can resolve on their own, but sometimes they also need to be treated
t
what types of antibiotic are most common for secondary opportunistic infections?
broad spectrum (amoxicillin, 3rd gen cephalosporins, clindamycin)
t/f there is a lot of debate over if antimicrobials can cause contraceptive failure leading to pregnancy
true
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
the hormones in birth control pills are metabolized by what enzymes?
CYP
how may Rifampin lead to contraceptive failure?
induce CYP
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
what are 3 proposed mechanisms of antibiotics leading to contraceptive failure?
- CYP induction
- reduced GI absorption of BC due to diarrhea
- reduction in enterohepatic circulation by causing reduced oral F of BC
what is enterohepatic circulation?
process by which bacteria in the GI tract increase the F of drugs
MO in the GI tract use ___ as a nutrient source
hormone metabolites
explain the process of enterohepatic circulation with estrogen in BC pills as an example substrate
- estrogen orally = subject to 1st pass metabolism in the liver
- sulfate metabolite is produced from liver metabolism
- metabolite goes into GI tract where bacteria take the sulfate and spit the estrogen back into the GI tract
- recycled estrogen can be reabsorbed and some to systemic and some remetabolized
t/f there is no concrete evidence that antibiotics except rifampin cause contraceptive failure, but it is best practice to warn patients
true
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
