Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
100 Cards in this Set
- Front
- Back
|
Sulfonamide mechanism
|
competitively inhibits PAB in folate synthesis = defective folate
|
|
|
If a patient is treated with sulfonamide and also takes supplemental folic acid, why will the sulfonamide not work?
|
sulfonamide competes with PAB in folic acid synthesis to inhibit proper folic acid synthesis so bacterial cells cannot make nucleosides using THFA. Sulfonamides inhibit synthesis of folic acid, not utilization; depend on growth of bacteria
|
|
|
What is a bactericidal agents?
|
kills bacteria rapidly
|
|
|
What are bacteriostatic agents?
|
reversibly inhibit bacterial growth
|
|
|
Even though bacteriostatic drugs are not permanently killing the bacteria, why are they sometimes preferred?
|
some of them act faster. erythromycin (static) will stop an toxin synthesis quickly than penicilin (cidal), but long term cidal is normally better
|
|
|
What is a therapeutic index?
|
ratio between effective dose and toxic dose
|
|
|
A drug has a low therapeutic index. Is this good or bad?
|
bad, there is a small difference in the amount of drug that is therapeutic vs. lethal. easy to overdose
|
|
|
Trimethroprim function
|
block folic acid utilization; blocks DHFR enzyme so THF (FH4) cannot be made
|
|
|
How do beta lactam drugs (penicillin) enter bacterial cells?
|
side chains on the B-lactam ring can penetrate the outer membrane of gram negative bacteria; interaction with PBP (penicillin binding proteins)
|
|
|
What are B-lactamases?
|
enzymes that can attack the B-lactam ring of B-lactam antibiotics (the ones that inhibit murein synthesis)
|
|
|
In gram positive bacteria, where is B-lactamase found?
|
ECM of bacterial cell; leads to high resistance since B-lactam drugs get attacked before they even get into the cell; produced only when exposed to antibiotic, can increase production to combat increased antibiotic
|
|
|
In gram negative bacteria, where is B-lactamase found?
|
periplasm; constitutively produced at steady rate/do not increase production with increasing antibiotic
|
|
|
Why can penicillin no longer be used as a universal antibiotic for gonorrhea?
|
the gene for B-lactamase has now been found on a transposon (part of a gene that can jump around between any gonorrhea strains)
|
|
|
Why is MRSA (methicillin resistant staph A) so resistant?
|
methicillin was the B-lactam drug that was not supposed to have resistance against it because it was immune to B-lactamase activity. but MRSA has defective pores so the methicillin drug can't even enter the bacterial cell/alter PBPs.
|
|
|
In vancomycin resistant strains, what compound is substituted in place of an amino acid?
|
lactate replaces alanine (D-ala--D-lac). vancomycin normally binds to alanine, but cannot bind to lactate
|
|
|
Quinolone antibiotics inhibit...
|
DNA gyrase (in gram +) and topoisomerase 4 (in gram -)
|
|
|
How might a bacteria develop resistance to quinolone drugs?
|
quinolone drugs inhibit DNA gyrase or topoisomerase;mutate genes encoding gyrase/topoisomerase so drug doesnt bind; if the bacteria develops an efflux pump, it can pump the drug out of the cell
|
|
|
Mechanism of oxazolidinones (linezolid)
|
bind to 50s subunit of bacterial ribosomes to prevent protein synthesis
|
|
|
Aminoglycosides bind to what to achieve their therapeutic effect?
|
bind to 30s subunit of ribosomes to inhibit protein synthesis; use one way 2-stage active transport to get through cell membrane; inactivate by modifying enzymes ,add acetyl or adenyl or phosphoryl grp to drug rendering inactive
|
|
|
How does tetracycline resistance usually develop?
|
bacteria develop a pump to push out the drug after it is taken in;
|
|
|
How does macrolide (erythromycin) resistance occur?
|
efflux pump; ribosome modification by methylase, methylation of 23s subunit, making the 50s unit resistant to macrolide binding.
|
|
|
Telithromycin is a macrolide that does not have any resistant strains yet. Why?
|
it binds to the 23s unit to prevent methylation of the 50s and allow normal blocking of the 50s unit. also resistant to efflux pumps
|
|
|
Oxazolidinones can develop resistance how?
|
target modification; linezolid can be defective against bacteria with 23s modifications in the rRNA of the 50s unit
|
|
|
What are polyenes?
|
bind to ergosterol in fungus
|
|
|
What is imidazole?
|
inhibits p450 demethylase = no sterol synthesis = weak cell wall
|
|
|
antimetabolite effective against a streptoccal infection in mice
|
prontosil
|
|
|
prontosil was the precursor to what drug
|
sulfonamides
|
|
|
substance in yeast that counteracts the actions of sulfonamides
|
PAB, p-aminobenzoic acid
|
|
|
relationship between amounts of sulfonamides administered and amounts of PAB created is called what
|
competitive inhibition
|
|
|
PAB is a constituitent of what vitamin
|
folic acid
|
|
|
antagonism of sulfa by folic acid is what
|
noncompetitive
|
|
|
what is unique about body folic acid requirements
|
body requires preformed folic acid
|
|
|
what effect do sulfonamides have on folic acid
|
affect the synthesis, not the utilization, thats why body cells are not harmed
|
|
|
why can't bacteria use preformed folic acid
|
they do not contain a mechanism to uptake it
|
|
|
how and why do sulfoniamides work for bacterial killing
|
inhibits formation of folic acid, can take 16 daugter cells for effect to become evident because has enough preformed folic acid; requires cell growth to be effective
|
|
|
bactericidal
|
kills immediately
|
|
|
bacteriostatic
|
inhibit growth reversibly
|
|
|
when are bactericidal drugs better to use
|
when the body defenses are insufficient to clear the invading agents
|
|
|
what conditions are better for bactericidals
|
bacterial endocarditis, meningitis and agranulocytopenia
|
|
|
erythromycin is what class
|
bacteriostatic, inhibits protein synthesis
|
|
|
in what case would you want a static agent
|
when you would want to give the body defenses a chance to eliminate the organisms on its own with help; stops production of protein toxins quickly
|
|
|
is static vs cidal concrete for all organisms?
|
no
|
|
|
spectinomycin
|
static for e coli, cidial for gonococci
|
|
|
what is effective against e coli in vitro
|
rifampin
|
|
|
every agent is responsive against a defined ____ of what
|
spectrum of organisms
|
|
|
aminoglycosides are taken up poorly under what conditions
|
anaerobic
|
|
|
what antibiotic for UTI
|
nitrofurantoin:concentrates in urine
|
|
|
theraputic index
|
ratio between the effective and toxic dose
|
|
|
methotrexate
|
inhibitors of folic acid metabolism
|
|
|
topical antibiotics that harm host cell membranes
|
polymyxin and antifungal nystatin
|
|
|
sulfonamide side effect
|
diuretic, blood acidosis and alkaline urine, some also cause hypoglycemia
|
|
|
function of trimethoprim
|
blocks the function rather than the synthesis of folic acid
|
|
|
what enzyme does trimethoprim deactivate
|
dihydrofolate reductase
|
|
|
what is the principle behind the mechanism of tetracycline
|
relative sensitivity, bacteria will concentrate the antibiotic, mammal cells will not
|
|
|
how is extreme selectivity achieved
|
when the target is not present in the host, only the target organism
|
|
|
B-lactam and extreme selectivty
|
murein target is only present in bacterial cells walls
|
|
|
B lactam antibiotics are known as what class of drugs
|
broad spectrum antibiotics
|
|
|
what type of microbes are B-lactams effective against
|
gram negative
|
|
|
3rd gen cephalosporins have what advantages
|
works on pseudomonas, h. influenzae and penetrate CNS - useful for gram negative meningitis
|
|
|
what is the principle mechanism of b-lactam resistance
|
inactivating enzymes
|
|
|
what kind of b-lactamaes do gram positive produce
|
extracellular
|
|
|
why is b-lactam ineffective against gram positive
|
because they release and produce more lactamases the more antibiotic comes into contact with positive wall
|
|
|
where are b-lactamses found in gram negative
|
in the periplasm or bound to inner membrane
|
|
|
why is it effective against gram negative
|
b-lactamases are produced at a constant rate, cant be increased
|
|
|
b-lactam resistance is common in what genus
|
staphylococci
|
|
|
how is b-lactamase resistance gene transferred from one bacteria to another
|
transposon via plasmid bridge
|
|
|
what do b-lactams have to pass through in order to hit PBP
|
outer membrane pores in gram negative bacteria
|
|
|
what is a PBP
|
penicillin binding protein
|
|
|
penicillin resistant step pneumoniae and methicillin resistant staph aureus come from what resistance mechanism
|
modification of PBPs
|
|
|
what are extensively modified PBP bacteria referred to as
|
MRSA
|
|
|
what is used to treat MRSA
|
cell wall inhibiting glycopeptides, vancomycin
|
|
|
why are some strains of pneumococci and staphylococci inhibited rather than killed by b lactam
|
partial resistance called tolerance
|
|
|
what type of bacteria is vancomycin used for
|
gram positive; given IV
|
|
|
how is vancomycin administered
|
intravenously
|
|
|
what is the vancomycin target
|
d-alanine-d-alanine (resistance is due to change to d-alanine-d-lactate)
|
|
|
what bacteria has vancomycin resistance
|
enterococcus
|
|
|
VRE and VRSA
|
vancomycin resistant enterococcus and s aureus, very hard to treat
|
|
|
how do quinolone antibiotics work
|
inhibit bacterial topoisomerases
|
|
|
gram negative and gram positive topoisomerase
|
negative - topoisomerase IV ; positive - dna Gyrase
|
|
|
quinolone used for gram negative and positive effectiveness
|
fluoroquinolone
|
|
|
what is one of the principle methods of quinolone resistance
|
efflux pumps
|
|
|
what is the basis for the effectiveness against bacteria with antiribosomal antibiotics
|
eukaryotic and bacteria have different ribosomes to enable different targets
|
|
|
what are two major antiribosomal antibiotics
|
erythromycin, streptomycin
|
|
|
what does tetracycline target
|
mammalian and bacterial ribosomes invivo
|
|
|
how do oxazolidinones work
|
bind to the 50s unit of bacterial ribosomes and prevent the assembly of the translation complex
|
|
|
what is aminoglycoside toxicity
|
renal tubules and inner ear
|
|
|
method of action for aminoglycoside
|
1. penetrate gram neg outer membrane 2. initiate two stage transport system (one-way) 3. BINDS TO 30S ribosome and ***** up the initiation site
|
|
|
two major resistance mechanisms for gram neg bacteria for aminoglycosides
|
modifying enzymes and obligate anaerobes (dont transport)
|
|
|
what is the most common method of tetracycline resistance
|
actively pumping the drug out of the bacteria
|
|
|
Fun Factoid: Macrolide antiobiotic names
|
erythromycin, clindamycin, azithromycin, clarithromycin
|
|
|
can macrolides be pumped out of bacteria like tetracyclines?
|
yes
|
|
|
what is the most significant degree of macrolide resistance
|
methylation of the 23s ribosomal RNA, this enables the 50s transcription unit to becomes resistant to drugs
|
|
|
what antibiotic works inspite of the methylase produced by macrolide resistance
|
telithromycin, binds to two separate sites on 23s, can still inhibit 50s unit
|
|
|
what is the major completely synthetically derived antibiotic
|
oxazolidinones
|
|
|
how is oxazolidinone resistance mechanized
|
point mutations in bacterial 23s RNA of the 50s subunit, prevent binding to ribosome
|
|
|
why are therapeutics against animal parasites, viruses or fungi toxic
|
target human ribosomes as well
|
|
|
polyenes
|
bind to egosterol in the membranes of fungi
|
|
|
amphotericin B
|
yeasts are about 200 fold more sensitive to this polyene antibiotic than are human cells
|
|
|
imidazoles
|
target p450 demethylase, involved with sterol synthesis (anti fungal: given topically or systemically)
|
|
|
echinocandins
|
inhibit fungal cell wall B-glucan
|
