Cephamycins, Carbapenems

Question 1

What side group do cephamycins have that classify them as second generation

Answer 1

7a-methoxyl group

Question 2

What is the importance of the 7a-methoxyl group on cephamycins?

Answer 2

increases stability against beta lactamases

Question 3

What type of antibiotic is cefotetan?

Answer 3

cephamycin

Question 4

How is cefotetan administered and its spectrum of activity?

Answer 4

• parenterally, broad

Question 5

What is a byproduct of cefotetan?

Answer 5

N-methlythiotetrazole

Question 6

What does N-methylthiotetrazole cause?

Answer 6

• hypopromthrombinemia
• rxn similar to disulfram (vomiting if alcohol consumed)

Question 7

What type of antibiotic is thienemycin

Answer 7

natural carbapenem

Question 8

Why cant thienamycin be used as a drug?

Answer 8

• too reactive
• primary amino group attacks the beta lactam intermolecularly

Question 9

What overcomes the issue with the reactivity of thienamcyin

Answer 9

• N-mormiminoyl on imipenem prevents the intermolecular attack

Question 10

What is the structural difference between carbapenems and penicillins

Answer 10

• sulfur that is present in the thiazolidine ring of penicillins is replaced by a methylene group

Question 11

How does the replacement of the sulfur atom of the penicillins with a methylene group (carbapenems) effect reactivity of the beta lactam ring?

Answer 11

• this increases reactivity
• methylene is smaller than a sulfur
• so ring strain is greater in carbapenems

Question 12

What is the unique feature that imipenem has against beta lactamases?

Answer 12

• reacts and inhibits beta lactamases along with reacting with PBPs

Question 13

How is imipenem metabolized?

Answer 13

hydrolyzed by renal dehydropeptidase-1

Question 14

How can imipenem overcome hydrolysis by renal dehydropeptidiase-1?

Answer 14

• co-administration with cilastatin (dehysropeptidase-1 inhibitor)

Question 15

What type of antibiotic acitivity does imipenem with cilastatin have?

Answer 15

broad spectrum (magic bullets)

Question 16

Which carbapenem is a beta lactamase inducer?

Answer 16

imipenem

Question 17

How is imipenem with cilastatin administered?

Answer 17

parenterally

Question 18

How is the origin of monobactams different from penicillins and cephalosporins?

Answer 18

• monobactam antibiotics are totally synthetic
• sulfamic acid group takes place of the C-2 carboxyl group in penicillins and cephalosporins

Question 19

What is the structural feature of monobactams that allows them to be biologically active?

Answer 19

• sulfamic acid group
• electronegativity of this group activate the beta lactam ring toward chemical hydrolysis and to react with penicillin binding proteins

Question 20

What is the antibiotic spectrum of monobactams?

Answer 20

focuses almost completely on Gram negative bacteria

Question 21

What is an example of a monobactam?

Answer 21

Aztreonam

Question 22

How do monobactams react with transpeptidases?

Answer 22

• OH group of the PBP reacts with the double bonded oxygen on the beta lactam ring to open up the ring (ether formed)

Question 23

What is the cross allerginicity between monobactams and penicillins/cephalosporins?

Answer 23

• only reported with ceftazidime
• ceftazidime has identical oxime ether sidechain