Antibiotics - 3/4

Question 1

What does ticarcillin treat?

Answer 1

is active against gram negative bacteria
- pseudomonas aeruginosa

has beta lactam ring, EWG (orally active), polar group (broad spectrum) and bulky group (beta lactamase resistant)

Question 2

What are the types of beta lactamases inhibitors?

Answer 2

clavulanic acid, tazobactam
- is acted on by beta lactamase and irreversibly inhibits it

are preferentially broken down and reacted with by the beta lactamase
- are sacrificial molecules

Question 3

How does beta lactamase inhibitors work?

Answer 3

act on 2 sites in active site of beta lactamase
- crosslinking causes irreversible inhibition

MOA
initial reaction with serine protease the lactamase receptor
- mimics penicillin group, opens beta lactam ring
amine group on the opposite side of the active site reacts with positively charged carbon
- nucleophilic attack
conjugate elimination reaction
- forms covalent bonds
causes release of amino acid

Question 4

What are the advantages of using cephalosporins?

Answer 4

are resistant to acid hydrolysis and beta lactamase activity
have broad spectrum of activity

Question 5

What are the disadvantages of cephalosporins?

Answer 5

are not as active as penicillins
- due to ring strain
- due to esterase hydrolysing the acetate groups resulting in loss of the ester
early cephalosporins have poor absorption
- requires administration by injection

3 position affects activity, absorption and metabolism
- hydroxyl is not a good leaving group

Question 6

What are the advantages and disadvantages of carbapenams?

Answer 6

are lactamase resistance
- due to inverse stereochemistry making beta lactamase not recognise it

increased reactivity
- due to increased ring strain

has the broadest spectrum of activity of all beta lactam antibiotics

poor GI absorption

Question 7

What is cycloserine? What is its mechanism of action?

Answer 7

broad spectrum antibiotic
- blocks transglycosidation prior to crosslinking

inhibits L-alanine racemase
- blocks inversion of stereochemistry to convert L-ala to D-ala

inhibits D-ala-D-ala ligase
- blocks linking of two D-ala to form a dipeptide

mimics D-alanine
- acts as a false substrate

Question 8

What is cycloserine used to treat?

Answer 8

mycobacterium tuberculosis

partial agonist of NMDA receptor in the brain

Question 9

What is the mechanism of action of vancomycin?

Answer 9

fixed conformation of the heptapeptide
- fixes the heptapeptide backbone in rigid conformation to enable selectivity for L-lys-D-ala-D-ala

attaches to the terminal L-lys-D-ala-D-ala tail
- dimerisation is possible

inhibits transglycosidase
- blocks growth of the peptide chain during cell wall synthesis by blocking disaccharide (NAM/NAG) addition

Question 10

What is vancomycin used to treat? What can it not be used to treat?

Answer 10

gram positive bacteria
- MRSA
- C.difficile

is inactive against gram negative bacteria