Med Chem - B lactamase inhibitors + Carbapenems + Monobactams

Question 1

name 4 combination products that contain a beta lactamase inhibitor

Answer 1

augmentin
unasyn
sulperazone
sultamicillin

Question 2

augmentin

Answer 2

amoxicillin + clavulanic acid

Question 3

sulperazone

Answer 3

cefoperazone + sulbactam

Question 4

sultamicillin

Answer 4

ampicillin + sulbactam
(another brand for unasyn)

Question 5

Unasyn

Answer 5

ampicillin + sulbactam
(another brand for sultamicillin)

Question 6

name 5 beta lactamase inhibitors

which 2 do NOT structurally mimic beta lactam antibiotics

Answer 6

clavulanic acid
sulbactam
tazobactam
avibactam
valorbactam

avibactam and valorbactam do not structurally mimic beta lactam

Question 7

which beta lactamase inhibitor contains boron

Answer 7

valorbactam

Question 8

in general, which are more resistant to beta lactamases – penicillins or cephalosporins?

Answer 8

cephalosporins, especially higher generations (3rd) have built in resistance

Question 9

true or false

beta lactamase inhibitors target PBP

Answer 9

false

THEY HAVE NO ANTIBACTERIAL PROPERTIES

Question 10

what was the natural starting point with carbapenems and what were the issues with it

Answer 10

thienamycin

had chemical and enzymativ instability

chemical instability in the side chain. terminal NH3+ is electron withdrawing, causing the beta carbon to sulfur to be e- deficient and electrophilic. this will cause sulfur to attack the beta carbon and the reaction will occur because NH3+ is a good leaving group. side chain spontaneously falls apart

enzymatic instability because the beta lactam ring is hydrolyzed by a human renal enzyme called DHP1

Question 11

imipenam

Answer 11

chemical instability of thienamycin was fixed by adding a terminal atom.
however, enzymatic instability still there

to fix, was combined with CILASTATIN which protects imipenem from hydrolysis

THIS COMBINATION PRODUCT OF IMIPENEM + CILASTATIN IS CALLED PRIMAXIN

Question 12

meropenem

Answer 12

fixed both issues of thienamycin

no chemical instability because while sulfur and N are still 2 atoms apart, the N is part of a cyclic ring for addtional protection

no enzymatic instability because a METHYL GROUP was added onto the 5 membered ring, providing DHP-1 resistance

Question 13

what can meropenem be combined with and what is the brand name of this combination product

Answer 13

meropenem + vaborbactam
called VABOMERE

vaborbactam is a non beta lactam, boron containing beta lactamase inhibitor.it enhances the action of meropenem by protecting it from certain serine B-lactamases like klebsiella pneumoniae carbapenemase

Question 14

true or false

vaborbactam does not have any antibacterial activity

Answer 14

TRUE

Question 15

the vaborbactam component of vabomere is a ________ ________ inhibitor that protects meropenem from degredation

Answer 15

non-suicidal beta lactamase inhibitor

Question 16

what was the 1st successful carbapenem that fixed both issues of thienamycin (chemical and enzymatic instability

Answer 16

meropenem

Question 17

name 4 carbapenems

what was natural prototype

Answer 17

natural prototype = thienamycin

meropenem
imipenem
etrapenem
doripenem

Question 18

which has more hydrophilic substituents and which has more lipophilic substituents between doripenem and etrapenem

Answer 18

etrapenem has more lipophilic

doripenem has more hydrophilic

Question 19

structurally, what are monobactams

Answer 19

monocyclic beta lactams

Question 20

1 and only example of a monobactam

Answer 20

aztreonam

Question 21

how are monobactams able to have sufficient beta lactam activity, without the beta lactam ring being fused with another ring?

Answer 21

the sulfate substituent (SO3-) gives the structure necessary beta lactam activation

Question 22

quinolones are bactericidal or static??

explain

Answer 22

rapidly bactericidal

bc they inhibit DNA gyrase (topoisomerase II) and topoisomerase 4 which are key enzymes for dictating the conformation of DNA

Question 23

why do we say fluoroquinolones have a unique mechanism of action

Answer 23

their target is inside the bacteria

Question 24

explain the progressive discovery of fluoroquinolones

Answer 24

started with nalidixic acid (not a true quinolone)

structurally modified to oxolinic acid – a true quinolone, but still not good enough

NORFLOXACIN was created, which is considered the prototype for 2nd gen quinolones (aka fluoroquinolones) has a fluorine at the 6 position which is a universal characteristic of 2nd gen quinolones (fluoroquinolones)

Question 25

name 3 macrolides

Answer 25

erythromycin azithromycin clarithromycin

Question 26

explain the chemical structure of macrolides

Answer 26

large (14-15 membered) lactone ring with a glycosidically linked amino sugar

Question 27

MOA of macrolides

Answer 27

protein synthesis inhibitor by binding to 50s ribosomal subunit bacteriostatic

Question 28

3 SAR components for macrolides what was the prototype?

Answer 28

prototype was erythromycin decosamine cladinose lactone (ester linkage in cyclic form)

Question 29

name a ketolide

Answer 29

telithromycin

Question 30

which has a lower incidence of developing resistance and why - macrolides or ketolides?

Answer 30

ketolides because of the switch from 3-cladinose to 3-ketone in ketolides thus, methylase gene expression of bacteria does NOT induce resistance

Question 31

true or false telithromycin is for oral administration

Answer 31

true

Question 32

MOA of ketolides

Answer 32

same as macrolides inhibit protein synthesis by binding 50s ribosomal subunit

Question 33

explain the characteristics of fidaxomicin

Answer 33

macrocyclic, but NOT a macrolide because there has to be a cyclic ester and amino sugar but fidaxomicin does NOT have an amino sugar extremely narrow spectrum and administered orally for c diff infection

Question 34

MOA fidaxomicin

Answer 34

inhibits bacterial RNA polymerase SELECTIVELY eradicates c diff with minimal dectruction to healthy flora

Question 35

fidaxomicin is _____ derived

Answer 35

NATURALLY

Question 36

fidaxomixin is part of a new class of ______ spectrum ____ antibiotics

Answer 36

narrow spectrum macrocyclic antibiotics (but NOT a macrolide - no amino sugar)

Question 37

bezlotoxumab

Answer 37

human monoclonal antibody designed to prevent the recurrence of c diff infection

Question 38

name 2 lincosamides

Answer 38

lincomycin clindamycin

Question 39

lincosamides are ____ containing

Answer 39

sulfur

Question 40

MOA lincosamides include whether bacteriostatic or cidal

Answer 40

bacteriostatic protein synthesis inhibitors binds 50s subunit (same as macrolides - remember MLS)

Question 41

name 6 aminoglycosides

Answer 41

tobramycin neomycin kanamycin amikacin streptomycin gentamicin

Question 42

MOA aminoglycosides cidal or static?

Answer 42

bactericidal binds 30s ribosomal subunit

Question 43

true or false aminoglycosides are primarily active against gram (+)

Answer 43

FALSE gram (-)

Question 44

how are aminoglycosides administered and why

Answer 44

parenteral or topical - NOT ORAL bc of basic alkyl amines

Question 45

concerns with aminoglycosides

Answer 45

because of basic character, can have strong ionic interaction with anions in otic and renal compartments, causing otic and renal toxicitiy

Question 46

MOA tetracyclines static or cidal?

Answer 46

static binds 30s subunit

Question 47

clinical concerns with tetracyclines

Answer 47

under 8 yrs old - permanent teeth staining also drug drug interaction with metal ions - *milk, iron, antacids

Question 48

briefly explain structure of tigecycline

Answer 48

minocycline + 9-glycylamido moeitiy this 9-glycyl amido gives it enhanced activity

Question 49

MOA tigecycline

Answer 49

same as tetracycline bacteriostatic - binds 30s subunit, blocking entry of amino-acyl tRNA into A site of ribosome

Question 50

color of tigecycline

Answer 50

oragee

Question 51

differentiate between resistance of tetracycline vs tigecycline

Answer 51

tigecycline has less resistance bc not affected by ribosomal protection or efflux of the drug (while tetracyclines are susceptible to these)

Question 52

2 tetracycline derivatives and name the difference (structurally)

Answer 52

tigecycline and eravacycline tigecycline has addition of 9-glycylamido moeity on minocycline eravacycline has 2 changes. fluorine atom at C7 and pyrrolidinoacetamido on C9 (both on D ring!!) BOTH have better resistance profile