Cephamycins, Carbapenems Flashcards
What side group do cephamycins have that classify them as second generation
7a-methoxyl group
What is the importance of the 7a-methoxyl group on cephamycins?
increases stability against beta lactamases
What type of antibiotic is cefotetan?
cephamycin
How is cefotetan administered and its spectrum of activity?
- parenterally, broad
What is a byproduct of cefotetan?
N-methlythiotetrazole
What does N-methylthiotetrazole cause?
- hypopromthrombinemia
- rxn similar to disulfram (vomiting if alcohol consumed)
What type of antibiotic is thienemycin
natural carbapenem
Why cant thienamycin be used as a drug?
- too reactive
- primary amino group attacks the beta lactam intermolecularly
What overcomes the issue with the reactivity of thienamcyin
- N-mormiminoyl on imipenem prevents the intermolecular attack
What is the structural difference between carbapenems and penicillins
- sulfur that is present in the thiazolidine ring of penicillins is replaced by a methylene group
How does the replacement of the sulfur atom of the penicillins with a methylene group (carbapenems) effect reactivity of the beta lactam ring?
- this increases reactivity
- methylene is smaller than a sulfur
- so ring strain is greater in carbapenems
What is the unique feature that imipenem has against beta lactamases?
- reacts and inhibits beta lactamases along with reacting with PBPs
How is imipenem metabolized?
hydrolyzed by renal dehydropeptidase-1
How can imipenem overcome hydrolysis by renal dehydropeptidiase-1?
- co-administration with cilastatin (dehysropeptidase-1 inhibitor)
What type of antibiotic acitivity does imipenem with cilastatin have?
broad spectrum (magic bullets)
Which carbapenem is a beta lactamase inducer?
imipenem
How is imipenem with cilastatin administered?
parenterally
How is the origin of monobactams different from penicillins and cephalosporins?
- monobactam antibiotics are totally synthetic
- sulfamic acid group takes place of the C-2 carboxyl group in penicillins and cephalosporins
What is the structural feature of monobactams that allows them to be biologically active?
- sulfamic acid group
- electronegativity of this group activate the beta lactam ring toward chemical hydrolysis and to react with penicillin binding proteins
What is the antibiotic spectrum of monobactams?
focuses almost completely on Gram negative bacteria
What is an example of a monobactam?
Aztreonam
How do monobactams react with transpeptidases?
- OH group of the PBP reacts with the double bonded oxygen on the beta lactam ring to open up the ring (ether formed)
What is the cross allerginicity between monobactams and penicillins/cephalosporins?
- only reported with ceftazidime
- ceftazidime has identical oxime ether sidechain
