Antibiotics Flashcards
What are some 30S inhibitors?
Aminoglycosides
Tetracycline
Are
linezolid
macrolides
chloramphenicol
clindamycin
quinupristin/dalfopristin
30S or 50S inhibitors?
50S inhibitors
*NOTE* linezolid, tetracycline and chloramphenicol interfere with mitochondrial ribosomes - do have effect on us, ie, bone marrow suppression.
What part of translation do linezolid and aminoglycosides inhibit?
Initiation
What part of translation do aminoglycoside, tetracycline, macrolide, chloramphenicol, clyndamycin, quinupristin/dalfoprisitin inhibit?
Elongation
Where else does aminoglycoside inhibit translation?
termination
Are most ribosome inhibitors bacteriostatic or bacteriocidal?
how about things that affect the cell wall?
bacteriostatic.
those would be bactericidal
What do linezolid, tetracycline, and chloramphenicol interfere with?
mitochondrial ribosomes (bone marrow suppression)
What are the steps of prokaryote translation initiation?
1) Initiation factors associate with the 30S ribosomal subunit.
2) Formylmethionine initiator tRNA and mRNA bind to 30S subunit.
3) 50S ribosome then binds and you have the complete initiation complex.
Where does Linezolid bind?
P-site on the 50S subunit
where do aminoglycosides bind and what do they do?
bind to 30S ribosome and freeze initiation complex
Elongation:
Aminoacyl tRNA is inserted in the acceptor site. ____________ interfere here and prevent aminoacyl tRNA attachment to the acceptor site.
TETRACYCLINES
Elongation:
- The peptide bond is formed. ____________ inhibits peptide bond formation.
Chloramphenicol
Elongation:
- fmet tRNA is released from the P site. In prokaryotes, an exit site called the E site binds tRNA after it’s displaced from the P site
- Translocation. A dipeptide tRNA moves from the A to the P site and the ribosome moves one codon along the mRNA. _______________________________ inhibit translocation.
- Another amino acyl tRNA is put in the A site and elongation continues.
Macrolides, Streptotagmins, Clindamycin
what antibiotics should you not use with newborns?
Chloramphenicol (can’t glucuronidate)
Erythromycin (piloric stenosis)
Sulfonimides
What antibiotics can you not use in children?
Tetracyclines
Fluoroquinolones
What antibiotics should you not use during pregnancy?
Tetracycline
Aminoglocosides,
Clarithromycin
Fluoroquinolones
Chloramphenicol
Sulfonimides
What do you need to do with antibiotics for the elderly?
Adjust for reduced renal funtion:
the half life of
beta-lactams
aminoglycosdes
and fluoroquinolones
will be increased
Where do Aminoglycosides
Streptomycin
Neomycin
Amikacin
Gentamicin
Tobramycin
do in Protein Synthesis?
Are they bactericidal, bacteriostatic?
BacterioSTATIC…act on 30S ribosome
What do the Tetracyclines -
Doxycycline,
Minocycline
Demeclocycline
Tetracycline
do in protein synthesis?
Are these bacteriostatic or bactericidal?
inhibit - act on 30S Ribosome
BacterioSTATIC
Where do Macrolides -
erythromycin
azithromycin
clarithromycin
cindamycin
chloramphenicol act in Protein Synthesis?
Are they bacteriostatic or bactericidal?
act on 50S ribosome…
Bacteriostatic
Resistance mechanism that prevents drug from reaching its target in
Beta-lactams
Rifampin
Fluoroquinolones
Sulfonamides
Trimethoprim
Linezolid
Aminoglycosides
Erythromycin, clindamycin, quinupristin/dalfopristin
Tetracyclines
are due to:
alteration of target
Beta-lactams – altered penicillin binding proteins (MRSA)
Vancomycin- altered target
Rifampin - DNA dependent RNA polymerase
Fluoroquinolones - DNA topoisomerase II or IV
Sulfonamides - Dihydropteroate synthetase
Trimethoprim - Dihydrofolate reductase
Linezolid – altered ribosome
Aminoglycosides – altered ribosome (uncommon)
Erythromycin, clindamycin, quinupristin/dalfopristin – methyltransferase modified ribosome
Tetracyclines – production of proteins that interfere with ribosomal binding
Resistance mechanism that prevents drug from reaching its target in
Sulfonamindes
is due to:
Upregulation of target or its substrate
Resistance mechanism that prevents drug from reaching its target in
penicillins
Cephalosporins
Aminoglycosides
Chloramphenicol
Tetracyclines
Macrolides
Clindamycin
quinupristin/dalfoprintin, metronidazole
is due to:
Enzymatic alteration of the antibiotics
this can sometimes occur in Bacitracin and Polymyxins as well
Which drugs are reserved for difficult to treat drug resistant bacteria?
(Like MRSA or VRE - vancomycin resistant enterococcus)
5th gen cephalosporin- ceftaroline,
vancomycin,
TMP-SMX,
daptomycin,
Quinupristin-Dalfopristin,
Linezolid
Dihydropteroate synthetase targeted
Sulfonamides
Production of proteins that interfere with ribosomal bindng
tetracyclines
Resistance mech that prevent drug from reaching its target in
Tetracyclines
Sulfonamides
Aminoglycosides
Chloramphenicol
is due to:
primarily decreased uptake
Resistance mechanism that prevents drug from reaching its target in
Cephalosporins
Aztreonam
Tetracyclines (most impt), minocycline the exception
Macrolides
Quinupristin/dalfopristin
Fluoroquinolones
Sulfonamides
is:
increased efflux
What are some differences between RNA and DNA translation?
RNA starts with formyl-methionine and the Shine Delgarno Sequence
DNA starts with just methionine…invovles a 5’Cap
What is notable about quinupristin/dalfopristin?
They’re 2 seperate drugs, but always used in combination
What antibiotic inhibits at all 3 steps of mRNA -> protein translation?
aminoglycosides (which is why they’re bacteriocidal - most ribosome inhibs. are bacteriostatic: they just interfere with one step)
What are concentration-dependent drugs?
Concentrations > 10 times above the MIC most effective at killing the organism
What are time-dependent drugs?
effect depends on time above the MIC
are aminoglycosides time or concentration dependent?
Concentration - they’re administered as a single large dose
Are B-lactams time or concentration-dependent?
Time - must have multiple doses
What drugs should be used on Mycoplasma pneumonia?
atypical pneumonia - use
Doxycycline
Azithromycin
Levofloxacin
(B-lactams not effective)
What should you use for Lymes?
amoxycillin or doxycycline….use Johns Hopkins guide
Enterococcuw drug resistance examples
(Gram + organism)
What agents may cause hemolysis in patients with glucose-6-phosphate dehydrogenase deficiency?
sulfonamides (trimethoprim/sulfamethoxazole)
which antibiotic may cause seizures?
beta-lactam (esp. carbapenems)
what antibiotic may cause hepatotoxicity?
rifampin
what antibiotic may cause nephrotoxicity?
sulfonamides
aminoglycosides
vancomycin
what antibiotic may cause Ototoxicity?
aminoglycosides
vancomycin
what antibiotic may cause QT interval prolongation?
macrolides, fluoroquinolones
what antibiotic may cause anemia?
chloramphenicol
trimethoprim
what antibiotic may cause arthralgia?
quinupristin/dalfoprisin
fluoroquinolones
what antibiotic may cause disulfiram-reaction when taken with alcohol?
metronidazole
2nd gen. cephalosporin w/methylthiotetrazole groups
what antibiotic may cause superinfections?
clindamycin
fluoroquinolones
3rd gen. cephalosporin
ampicillin
Which drugs are patients commonly hypersensitive to?
sulfonamides (shouldn’t take other sulfa drugs like diuretics)
B-Lactam (can use skin test to see, and then work on desensitization)
clindamycin
what are common drug-drug interactions?
rifampin induces drug metabolizing enzymes (uses up other drugs faster)
clarithroycin and erythromycin inhib. hepatic metabolism
Why treat with Trimethoprim-Sulfamethoxazole?
Inhibits multiple steps in folate synthesis
Why treat with Aminoglycoside+Penicillin?
Penicillin increases permeability of cell membranes increasing the ability of aminoglycosides to enter the cell
Why are
Ampicillin-sulbactam,
Amoxicillin-clavulanate,
Piperacillin-tazobactam,
Ticarcillin-clavulanate
Imipenem-cilastatin
used in sets like that?
Addition of inhibitors to prevent degradation of the enzyme
(for example, that last set blocks renal dehydropeptidase)
What happens if you use Vancomycin and Aminoglycosides together?
each alone have some nephrotoxicity. If given together you get marked renal impairment.
Should you use penicillin or penicillin + tetracycline in treating pneumoccal meningitis?
Penicillin - 21% mortality
Penicillin + Tetracycline - 79% mortality
(antagonism occurs)
