Bacterial Protein Synthesis Inhibitors Flashcards
what is the major difference between bacterial cell protein synthesis and mammalian cell protein synthesis?
bacteria have 70S ribosomes while mammals have 80S ribosomes
what were the first three inhibitors of bacterial protein synthesis?
aminoglycosides, tetracylines, and chloramphenicol
to which class of Ab does erythromycin belong?
macrolide
please identify the following as either broad spectrum, moderate, or narrow: chloramphenicol; linezolid; macrolides; streptogramins; ketolides; tetracyclines; lincosamides
broad; narrow; moderate; narrow; moderate; broad; narrow
with the exception of which, do the bacterial protein synthesis inhibitors bind on the 50S ribosomal unit?
tetracyclines - these bind to the 30S ribosomal unit; remember, binding to the 30S prevents binding of tRNA to mRNA
which drug am I? i bind to the 50S subunit and constrict the exit channel on the ribosome.
streptogramins
true or false: linezolid is mainly bactericidal
false; mainly bacteriostatic - it binds to a unique site on 50S which inhibits initiation by blocking formation of tRNA ribosome and mRNA ternary complex.
what is unique about the MOA of chloramphenicol in terms of its effect on mammalian cells?
while it does NOT bind to the 80S ribosomal unit of our cells, it CAN however inhibit the function of mitochondrial cells which contain 70S ribosomal units
true or false: chloramphenicol rapidly crosses both the placenta and BBB
true
most of chloramphenicol is inactivated by which hepatic enzyme?
glucorunosyltransferase
true or false: chloramphenicol is typically bactericidal
false; bacteriostatic
true or false: chloramphenicol is very active against chlamydia
false
how is resistance to chloramphenicol mediated?
plasmid-mediated through the formation of acetyltransferases that inactivate the drug.
true or false: b/c of its toxicity chloramphenicol has very few uses as a systemic drug
true
which drug is commonly used as a backup drug for severe infections caused by salmonella and for the tx of pneumococal and meningococcal meningitis in beta lactam sensitive persons?
chloramphenicol
define gray baby syndrome
occurs in infants; characterized by decreased RBCs, cyanosis, and CVS collapse.
how does chloramphenicol affect the following drugs: phenytoin, tolbutamide, and warfarin?
increases the elimination half lives (b/c it inhibits hepatic drug metabolizing agents)
true or false: tetracyclines have a small tissue distribution and do not cross the placenta
FALSE; have a wide tissue distribution and do cross the placenta
with the exception of which drug are most tetracyclines eliminated primarily in the urine?
doxycycline which is excreted mainly in the feces
true or false; tigecyline can be administered either orally, IV or IM.
false; it has been formulated only for IV use; note, it is eliminated in the bile and has a half life of approx 30 to 36 hours
what are the two main methods of resistance against tetracyclines?
- development of mechanisms for active extrusion (efflux pumps) and 2. the formation of ribosmal protection proteins that interfere with binding.
true or false: the mechanisms of resistance to tetracycline confers resistance to tigecycline in most organism
false - with the exception of multi drug efflux plumps of proteus and pseudomonas species
what is the DOC to treat both VRE and MRSA?
tigecycline
fetal exposure to this Ab may lead to tooth enamel dysplasia and irregularities in bone growth.
tetracyclines
the use of outdated tetracyclines has been attributed to what renal disease?
Fanconi syndrome, a form of renal tubular acidosis
true or false: tetracyclines are in more ways than one directly nephrotoxic
false; not at all directly nephrotoxic, but may exacerbate preexisting renal dysfunction
what is a unique side effect of demeclocycline?
enhanced sensitivity to UV light
true or false: azithromycin, despite having good oral availability, often has its absorption impeded by the presence of food.
true
what makes azithromycin’s distribution to most body tissues unique?
the levels achieved in tissues and in phagocytes are MUCH higher than those in plasma
what are the two methods of resistance to macrolides?
- efflux pumps 2. production of a methylase that adds a methyl group to the ribosomal binding site
true or false: cross-resistance between individual macrolides is complete
true
of the macrolides, which has the longest half life?
azithromycin - it is eliminated slowly (2 to 4 days) mainly in the urine and unchanged
of the macrolides, which is eliminated via hepatic metabolism?
clarithromycin
of the macrolides, which is eliminated via bile excretion?
erythromycin
which macrolide, given orally has proven to be as effective as vancomycin in tx for C. diff?
fidaxomicin
which of the macrolides inhibits several forms of hepatic cytochrome P450?
erythromycin
which of the macrolides is known to have the LEAST drug drug interactions?
azithromycin - remember, the lactone ring structure is slightly different and does NOT inhibit cytochrome p450
this drug is an example of a ketolide which has the same MOA as erythromycin.
telithromycin - it should be noted however that some macrolide resistant strains are actually susceptible b/c telithromycin binds more tightly to ribosomes and is also a poor substrate for efflux pumping
what effect does telithromycin have on the EKG?
prolongs QTc interval - in unrelated adverse effects it also causes hepatic dysfunction and is an inhibitor of CYP3A4
true or false: gram + aerobes are intrinsically resistant b/c of poor penetration through the outer membrane
false; it’s gram negatives NOT + (remember only the gram - have the outer membrane)
true or false: cross resistance btwn macrolides and clindomycin is common
true
clindomycin is recommended for prophylaxis of what?
endocarditis in valvular disease patients who are allergic to penicillin
clindomycin is often used in combo with ______ for the tx of AIDs related toxoplasmosis.
pyrimethamine
this class of Ab are very effective in tx of VRSA, VRE, and MRSA
streptogramins
streptogramins drug drug interactions runs very high - why?
b/c it inhibits cyp3a4 and increases plasma levels of many drugs
the first of a novel class of Ab (oxazolidinones) that is used for the tx of MRSA, PRSP, and VRE - resistance is very rare.
linezolid
what is the unique site on the 50S ribosomal unit that linezolid binds to?
23S
linezolid should be reserved for treatment of what types of infections? be specific
multi-drug resistant infections (gram +)
which of the bacterial protein synthesis inhibitors have been implicated in serotonin syndrome?
linezolid
