Term
carbepenems are a subgroups of beta lactam antibiotics
broad spectrum antibiotics
good stability against beta-lactamases
strong binding to essential PBPs
[image]
the beta lactam ring of carbepenems is MORE STRAINED THAN PENICILLIN'S. this is because of the double bond that is trying to force the N to be planar even though is is pyramidal.
more reactive and less stable in basic and acidic environments
also, chemical instability is related to the amino group which is a nucleophile that can undergo an intermolecular reaction with the beta lactam ring or with another molecule |
|
Definition
| characteristics of carbepenems |
|
|
Term
disadvantage: hydrolysis by dihydropeptidases
it is coadministered with cilastatin sodium which is an inactivator of dihydropeptidases |
|
Definition
what is a disadvantage of imipenem and what is the solution to this problem?
[image] |
|
|
Term
| the methyl group added to position 4 gives stability against dihydropeptidases |
|
Definition
why is meropenem not hydrolyzed by dihydropeptidases?
[image] |
|
|
Term
introduction of a 1 beta methyl group to the carbepenem skeleton enhances metabolic stability to renal dehydropeptidase-1 and leads to high antibacterial potency
(3S)-pyrrolidin-3-ylthio group at the C-2 position in the carbepenem skeleton are noted for their broad and potent antibacterial activity
[image]
doripenem |
|
Definition
|
|
Term
[image]
monobactams are more stable and LESS STRAINED as compared to penicillins and cephalosporins and carbepenems
has a methoxy group at position 3 like the cephamycins |
|
Definition
| characteristics of monobactams |
|
|
Term
[image]
Syn-Oximino functionality confers stability to hydrolysis by beta lactamases
aminothiazole group extends the spectrum to a wider range of gram - bacteria
carboxyl group enhances activity against pseudomonas aeruginosa
4-methyl group confers stability to hydrolysis by beta lactamases
sulfonic acid participates in PBP recognition |
|
Definition
|
|
Term
beta lactam ring fused to a 5 membered ring
carboxylic acid
NO SUBSTITUENTS IN THE 6 POSITION
[image] |
|
Definition
| characteristics of beta lactamase inhibitors |
|
|
Term
[image]
first there is acetylation of clavulanic acid (opening of the amide ring and formation of a covalent bond between beta lactamase and clavulanic acid)
K2:
rearrangement of the clavulanic acid to an open form (5 membered ring opens up)
serine 70 is always the first one to act, then serine 130 can also react with the rearranged clavulanic acid. end up with double hit inhibition of the beta lactamase
the enzyme is already inhibited by being attached to clavulanic acid at ser70 but it can get tied up even more by the other serine (completely inhibited)
the second bond is an ETHER bond (not an ester bond) that is more stable b/c you need more than water to hydrolyze it.
K1:
enzyme reaction with clavulanic acid
opens the ring
deacetylation that releases the enzyme
K1 is the recovery of the enzyme and destruction of the antibiotic
K2 should be much faster than K1 to inactivate the enzyme |
|
Definition
|
|
Term
very good inhibitory activity against class A beta lactamses
very little antibiotic activity
[image]
K5 should be the fastest to inhibit the enzyme b/c it forms a double hit
K4 reaction is bad b/c it is reversible and can go back to the acetylated enzyme which can be released |
|
Definition
|
|
Term
good affinity to most Class A and some Class D beta lactamases, and moderate activity against Class C
prepared synthetically
[image]
i - tazobactam inhibits the enzyme through an ether bond. single hit
ii - deacetylation of the enzyme, but still attached to ser130. showing a double hit, but the end product is only with ser130
iii - keto-type covalent bond between the enzyme and tazobactam. single hit |
|
Definition
|
|
Term
[image]
hybrid of a beta lactamase inhibitor and a beta lactam antibiotic |
|
Definition
[image]
sultamicillin
characteristics of this drug |
|
|
