Bacterial Protein Synthesis Inhibitors

Question 1

what is the major difference between bacterial cell protein synthesis and mammalian cell protein synthesis?

Answer 1

bacteria have 70S ribosomes while mammals have 80S ribosomes

Question 2

what were the first three inhibitors of bacterial protein synthesis?

Answer 2

aminoglycosides, tetracylines, and chloramphenicol

Question 3

to which class of Ab does erythromycin belong?

Answer 3

macrolide

Question 4

please identify the following as either broad spectrum, moderate, or narrow: chloramphenicol; linezolid; macrolides; streptogramins; ketolides; tetracyclines; lincosamides

Answer 4

broad; narrow; moderate; narrow; moderate; broad; narrow

Question 5

with the exception of which, do the bacterial protein synthesis inhibitors bind on the 50S ribosomal unit?

Answer 5

tetracyclines - these bind to the 30S ribosomal unit; remember, binding to the 30S prevents binding of tRNA to mRNA

Question 6

which drug am I? i bind to the 50S subunit and constrict the exit channel on the ribosome.

Answer 6

streptogramins

Question 7

true or false: linezolid is mainly bactericidal

Answer 7

false; mainly bacteriostatic - it binds to a unique site on 50S which inhibits initiation by blocking formation of tRNA ribosome and mRNA ternary complex.

Question 8

what is unique about the MOA of chloramphenicol in terms of its effect on mammalian cells?

Answer 8

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

Question 9

true or false: chloramphenicol rapidly crosses both the placenta and BBB

Answer 9

true

Question 10

most of chloramphenicol is inactivated by which hepatic enzyme?

Answer 10

glucorunosyltransferase

Question 11

true or false: chloramphenicol is typically bactericidal

Answer 11

false; bacteriostatic

Question 12

true or false: chloramphenicol is very active against chlamydia

Answer 12

false

Question 13

how is resistance to chloramphenicol mediated?

Answer 13

plasmid-mediated through the formation of acetyltransferases that inactivate the drug.

Question 14

true or false: b/c of its toxicity chloramphenicol has very few uses as a systemic drug

Answer 14

true

Question 15

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?

Answer 15

chloramphenicol

Question 16

define gray baby syndrome

Answer 16

occurs in infants; characterized by decreased RBCs, cyanosis, and CVS collapse.

Question 17

how does chloramphenicol affect the following drugs: phenytoin, tolbutamide, and warfarin?

Answer 17

increases the elimination half lives (b/c it inhibits hepatic drug metabolizing agents)

Question 18

true or false: tetracyclines have a small tissue distribution and do not cross the placenta

Answer 18

FALSE; have a wide tissue distribution and do cross the placenta

Question 19

with the exception of which drug are most tetracyclines eliminated primarily in the urine?

Answer 19

doxycycline which is excreted mainly in the feces

Question 20

true or false; tigecyline can be administered either orally, IV or IM.

Answer 20

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

Question 21

what are the two main methods of resistance against tetracyclines?

Answer 21

1. development of mechanisms for active extrusion (efflux pumps) and 2. the formation of ribosmal protection proteins that interfere with binding.

Question 22

true or false: the mechanisms of resistance to tetracycline confers resistance to tigecycline in most organism

Answer 22

false - with the exception of multi drug efflux plumps of proteus and pseudomonas species

Question 23

what is the DOC to treat both VRE and MRSA?

Answer 23

tigecycline

Question 24

fetal exposure to this Ab may lead to tooth enamel dysplasia and irregularities in bone growth.

Answer 24

tetracyclines

Question 25

the use of outdated tetracyclines has been attributed to what renal disease?

Answer 25

Fanconi syndrome, a form of renal tubular acidosis

Question 26

true or false: tetracyclines are in more ways than one directly nephrotoxic

Answer 26

false; not at all directly nephrotoxic, but may exacerbate preexisting renal dysfunction

Question 27

what is a unique side effect of demeclocycline?

Answer 27

enhanced sensitivity to UV light

Question 28

true or false: azithromycin, despite having good oral availability, often has its absorption impeded by the presence of food.

Answer 28

true

Question 29

what makes azithromycin’s distribution to most body tissues unique?

Answer 29

the levels achieved in tissues and in phagocytes are MUCH higher than those in plasma

Question 30

what are the two methods of resistance to macrolides?

Answer 30

1. efflux pumps 2. production of a methylase that adds a methyl group to the ribosomal binding site

Question 31

true or false: cross-resistance between individual macrolides is complete

Answer 31

true

Question 32

of the macrolides, which has the longest half life?

Answer 32

azithromycin - it is eliminated slowly (2 to 4 days) mainly in the urine and unchanged

Question 33

of the macrolides, which is eliminated via hepatic metabolism?

Answer 33

clarithromycin

Question 34

of the macrolides, which is eliminated via bile excretion?

Answer 34

erythromycin

Question 35

which macrolide, given orally has proven to be as effective as vancomycin in tx for C. diff?

Answer 35

fidaxomicin

Question 36

which of the macrolides inhibits several forms of hepatic cytochrome P450?

Answer 36

erythromycin

Question 37

which of the macrolides is known to have the LEAST drug drug interactions?

Answer 37

azithromycin - remember, the lactone ring structure is slightly different and does NOT inhibit cytochrome p450

Question 38

this drug is an example of a ketolide which has the same MOA as erythromycin.

Answer 38

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

Question 39

what effect does telithromycin have on the EKG?

Answer 39

prolongs QTc interval - in unrelated adverse effects it also causes hepatic dysfunction and is an inhibitor of CYP3A4

Question 40

true or false: gram + aerobes are intrinsically resistant b/c of poor penetration through the outer membrane

Answer 40

false; it’s gram negatives NOT + (remember only the gram - have the outer membrane)

Question 41

true or false: cross resistance btwn macrolides and clindomycin is common

Answer 41

true

Question 42

clindomycin is recommended for prophylaxis of what?

Answer 42

endocarditis in valvular disease patients who are allergic to penicillin

Question 43

clindomycin is often used in combo with ______ for the tx of AIDs related toxoplasmosis.

Answer 43

pyrimethamine

Question 44

this class of Ab are very effective in tx of VRSA, VRE, and MRSA

Answer 44

streptogramins

Question 45

streptogramins drug drug interactions runs very high - why?

Answer 45

b/c it inhibits cyp3a4 and increases plasma levels of many drugs

Question 46

the first of a novel class of Ab (oxazolidinones) that is used for the tx of MRSA, PRSP, and VRE - resistance is very rare.

Answer 46

linezolid

Question 47

what is the unique site on the 50S ribosomal unit that linezolid binds to?

Answer 47

23S

Question 48

linezolid should be reserved for treatment of what types of infections? be specific

Answer 48

multi-drug resistant infections (gram +)

Question 49

which of the bacterial protein synthesis inhibitors have been implicated in serotonin syndrome?

Answer 49

linezolid