Penicillins Dr. Roane

Question 1

What is ß-lactam?

Answer 1

Antibiotic
-Lactam: Carbonyl adjacent to a nitrogen
-> ß-Lactam (4-ring): nitrogen adjacent to the ß-carbon

-gamma (5-ring), delta (6-ring)

Question 2

Why is the R group next to the core of ß-lactams important?

Answer 2

-acid stability
-a spectrum of activity
-resistance to enzymatic breakdown

Question 3

How is Cephalosporin different from Penicillin?

Answer 3

-Cephalosporin has a 6-membered ring next to the ß-lactam ring

-2 substitution sites: acid stability, spectrum, resistance to breakdown
-> means more variability, more drugs

-Carbapenem has 3 sites for substitutes

Question 4

The function of Clavulinic Acid

Answer 4

-ß-lactam inhibitor (combined with amoxicillin -> Augmentin)
-It blocks ß-lactamases (enzymes) from destroying antibiotic ß-lactam

-has minor antimicrobial activity

Question 5

MOA of ß-lactams

Answer 5

-block the last steps of cell wall synthesis by binding to penicillin-binding-proteins PBPs (Transpeptidase)

-affinity of the drug determines the drug efficacy

Question 6

What are the peptidoglycans?

Answer 6

-Amino sugars (sugar with an amine)
-consists of N-acetylmuramic acid (NAM - with R) and N-acetylglucosamine (NAG)

-the peptide comes off of NAM and it will bind to another peptide that is coming off from another NAM

-Glycine will bind to Alanin of another NAM

Question 7

What are the targets of ß-lactams?

Answer 7

-Peptidoglycan polymers in the cell wall

-targets the Transpeptidase (covalent, suicide inhibition) that links the peptides between NAMs in the cell wall

-This polymer consists of sugar molecules and peptides attached to them -> lattice-network

Question 8

Why is ß-lactam able to bind and inhibit PBPs (Transpeptidases?

Answer 8

-Because the pharmacophore of ß-lactams mimics the structure of the peptide, which naturally binds to the Transpeptidase during cell synthesis

-2 Alanin in the peptide chain is structured at a 90° angle -> mimicking the ß-lactam ring

Question 9

What is the target of Vancomycin?

Answer 9

-Glucosyltransferase = PBP2
-it links NAG-NAM to the larger NAG-NAM polymer chain

Question 10

The function of PBPs?

Answer 10

-PBP1: Transpeptidation
-PBP2: Transglycosylation

Question 11

Other MOA of drugs effective against bacteria

Answer 11

-inducing the activity of autolysins
-autolysin: cell wall remodeling enzyme

-the faster the bacteria grows the more susceptible

Question 12

What are the Natural Penicillins?

Answer 12

Penicillin G (IV only)

Penicillin V (can be given orally)

Question 13

What is special about Antistaphylococcal penicillins?

Answer 13

They are resistant to ß-lactamases (cant be chewed up by bacterias enzyme)

-Cloxacillin, Dicloxacillin, Methicillin, Nafcillin, Oxacillin

Question 14

What are extended-spectrum penicillins?

Answer 14

-some activity against gram neg rods
-Ampicillin, Amoxicillin
-> not stable to ß-lactam inhibitor (unless you add clavulanic acid to Amoxicillin or sulbactam to Ampicillin)

Question 15

Name a drug that works against Pseudomonas aeruginosa
Antipseudomonal

Answer 15

-Indanyl carbenicillin

-Piperacillin + tazobactam (Pip-tazo)

-Ticarcillin + clavulanic acid

Question 16

How is reduced renal function detected?

Answer 16

-renal eGFR (glomerular filtration rate, < 50 ml/min)
OR
-plasma creatinine levels (normal value is close to 1)

-patients with impaired kidneys need reduced doses of drugs