Beta-Lactams

Question 1

Beta-Lactams Resistance

Answer 1

B-lactamase catalyzes the hydrolysis B-Lactam

Question 2

Beta-lactams MoA

Answer 2

inhibition of transpeptidase that “glue” the peptidoglycan strands together by cross linking

Question 3

What do B-lactams mimic?

Answer 3

D-Ala-D-Ala (so transpeptidase binds to it)

Question 4

Beta-Lactams Allergenicity

Answer 4

• 6-8% of pop
• cross reactivity between B-L’s
• B-L’s act as a hapten (inc antibodies = Ax rxn)

Question 5

Penicillin G (Benzyl PCN)

Answer 5

• Beta-lactamase sensitive
• G+
• Parenteral
• Caution in Asthma

Question 6

Penicillin V (Phenoxymethyl PCN)

Answer 6

• Beta-lactamase sensitive
• G+
• Oral
• more stable than PCN G in stomach b/c the electronegativity ether oxygen dec nucleophilicity of amide carbonyl

Question 7

Methicillin

Answer 7

• Beta-lactamase Resistant
• Parenteral
• resistant due to steric hindrance
• not stable in stomach b/c of electron donation (more nucleophilic)

Question 8

Nafcillin

Answer 8

• Beta-lactamase resistant
• parenteral
• more stable than methicillin in acid

Question 9

Dicloxacillin, Oxacillin, Cloxacillin

Answer 9

• Beta-lactamase resistant
• Oral
• Isoxazoles

Question 10

Ampicillin

Answer 10

• Beta-lactamase sensititve
• Broad spectrum
• oral
• Charged amino group = G- activity

Question 11

Amoxicillin

Answer 11

• beta-lactamase sensitive
• broad sprectrum
• oral
• Charged amino group = G- activity
• better oral absorption than ampicillin

Question 12

B-lactamase inhibitors MoA

Answer 12

acylate serine hydroxyl in B-lactamase -> B-lactamases can’t breakdown PCNs

Question 13

Clauvanate, Sulbactam, Tazobactam, Avibactam

Answer 13

B-lactamase inhibitors

Question 14

Piperacillin

Answer 14

• B-lactamase sensitive
• Broad spectrum
• Parenteral
• Added side chain looks like peptidoglycan = broader spectrum

Question 15

Cephalosporin Allerginicity

Answer 15

• 3% of pop
• less common/severe than PCNs

Question 16

Cephalexin

Answer 16

• 1st gen cepha
• oral
• G+
• unreactive CH3 on C-3 makes it more stable in stomach

Question 17

Cefazolin

Answer 17

• 1st gen cepha
• parenteral
• G+

Question 18

Cefuroxime

Answer 18

• 2nd gen cepha
• oral & parenteral
• G+ and some G-
• protect from light
• SYN oxime ether = resistant to B-lactamase

Question 19

Ceftazidime

Answer 19

• 3rd gen cepha
• Parenteral
• more G- than G+
• oxime ether = resistant to B-lactamase
• Charged pyridinium ring increases aqueous solubility

Question 20

Cefixime

Answer 20

• 3rd gen cepha
• Oral
• more G- than G+
• oxime ether = resistant to B-lactamase
• unreactive group at C-3 inc oral

Question 21

Cefepime

Answer 21

• 4th gen cepha
• Parenteral
• G- and G+
• Syn methoximine stabilizes against B-lactamase
• N-methylpyrrolidine is good leaving group, inc parenterally active

Question 22

Ceftaroline

Answer 22

• 5th gen cepha
• parenteral
• Ceftaroline fosamil (prodrug)
• broad spectrum
• resistant to B-lactamase
• charged N, inc G- activity

Question 23

Imipenem

Answer 23

• Carbapenems
• Parenteral
• broad spectrum
• N-formiminoyl derivative of thienamycin (thiena is too reactive to use)
• Sulfar atom in PCN is replaced by methylene
• inhibits B-lactamase
• hydrolyzed by dehydropeptidase-1
• Combo w/ CILASTATIN to inhibit D-1

Question 24

Aztreonam

Answer 24

• Monobactam
• Parenteral
• sulfamic acid makes it active/reacts with PBPs
• oxime ether = resistant to B-lactamse
• G- for severe infections
• No cross Ax w/ PCNs and Cepha (except Ceftazidime)

Question 25

Vancomycin

Answer 25

• Glycopeptide
• MoA: inhibitor of G+ cell wall biosynthesis
• G+ only
• Resistance: mut of peptidoglycan cell wall precursor
• Tx: MRSA
  AE: Red skin rash, nephrotoxic, ototoxic

Question 26

Oritavancin, Telavancin, Dalbavancin

Answer 26

• Lipoglycopeptides
• MoA: inhibits transpeptidase and transglycosylation
• Broad spectrum
• Dalba and Orita LONG t1/2, single dose

Question 27

Synercid

Answer 27

• 30% Quinupriston, 70% Dalfopriston
• static alone, cidal together agsinst MRSA