(MIDTERM) Beta-Lactam Antibiotics: Carbapenems & Monobactam Glycopeptide Antibiotics

Question 1

Naturally occurring Carbapenem from the bacterium Streptomyces cattleya

Answer 1

Discovery of Thienamycin

Question 2

Due to the drug’s instability in clinical use, the drug was chemically modified to produce more stable analogues

Answer 2

Discovery of Thienamycin

Question 2

Prototype Carbapenem:

Answer 2

Imipinem

Question 2

First carbapenem as an antibacterial drug

Answer 2

Imipinem

Question 3

Stable synthetic analogue of Thienamycin

Answer 3

Imipinem

Question 4

Approved for medical use in 1982

Answer 4

Imipinem

Question 5

Active against Gram-Positive and Gram-Negative organisms

Answer 5

Carbapenems

Question 5

CARBAPENEMS
______penem
______penem
______penem
______penem

Answer 5

DORI
IMI
ERTA
MERO

Question 5

Broad spectrum of activity

Answer 5

Active against Gram-Positive and Gram-Negative organisms

Question 6

Carbapenems;
Adverse Effects:

Answer 6

• Nephrotoxicity
• Hepatotoxicity
• GI Disturbances

Question 7

Can cross the BLOOD BRAIN BARRIER

Answer 7

Carbapenems

Question 8

____pinem + ______statin

Answer 8

IMIpinem + CILAstatin

Question 8

Role:
NO ANTIBACTERIAL ACTIVITY

Answer 8

Carbapenems

Question 9

MOA: Dehydropeptidase-1 (DHP-1) inhibitor

Answer 9

Carbapenems

Question 9

Only used to enhanced kinetics

Answer 9

NO ANTIBACTERIAL ACTIVITY

Question 10

• Present in kidneys
• Degrades the drug

Answer 10

Dehydropeptidase-1 (DHP-1) inhibitor

Question 11

Rrevents the breakdown of IMIpenem in the renal tubules, increasing its bioavailability and
effectiveness.

Answer 11

Carbapenems

Question 12

Reduces nephrotoxic metabolites that would otherwise accumulate

Answer 12

Carbapenems

Question 13

Synthetic Compounds

Answer 13

Monobactams

Question 14

There are NO known natural monobactams that are Clinically Effective

Answer 14

Synthetic Compounds

Question 14

A beta-lactam compound in which the β-lactam ring is alone and not fused to another ring (unlike in penicillin and cephalosporin)

Answer 14

Synthetic Compounds

Question 15

Does not posses a Bicyclic Ring System, thus, “Mono”

Answer 15

Monocylcic Beta-Lactam Ring

Question 15

Monocylcic Beta-Lactam Ring

Answer 15

Monobactams

Question 15

Confers stablility against most β-lactamases

Answer 15

Monocylcic Beta-Lactam Ring

Question 16

Selective Against Aerobic Gram-Negative Bacilli

Answer 16

Monobactams

Question 17

Monobactams Spectrum of Activity:_________

Answer 17

NARROW-SPECTRUM

Question 18

4 Selective Against Aerobic Gram-Negative Bacilli: "PEAK"

Answer 18

* Pseudomonas aeruginosa * Enterobacter * Acinetobacter baumannii * Klebsiella pneumoniae

Question 18

Monocyclic β-Lactam Ring Mechanism of Action: ______________

Answer 18

Selective Inhibition of Penicillin-Binding Protein 3 (PBP3)

Question 18

Inhibits Septal Peptidoglycan Synthesis

Answer 18

Selective Inhibition of Penicillin-Binding Protein 3 (PBP3)

Question 19

Prevent the formation of the septum (the dividing wall) during bacterial binary fission.

Answer 19

Selective Inhibition of Penicillin-Binding Protein 3 (PBP3)

Question 20

Effect: Non-dividing bacterial cells

Answer 20

Selective Inhibition of Penicillin-Binding Protein 3 (PBP3)

Question 21

Negatively charged sulfonic acid (-SO₃H) group at C2 mimics the carboxylate group in penicillins/cephalosporins but enhances affinity for Gram-negative

Answer 21

Sulfonic Acid (SO₃H)

Question 21

Increases penetration through the outer membrane of Gram-Negative bacteria

Answer 21

Negatively charged sulfonic acid (-SO₃H) group

Question 22

Similar to other Beta-lactam antibiotics

Answer 22

MOA of Aztreonam:

Question 22

The only commercially available monobactam antibiotic

Answer 22

Aztreonam

Question 23

This antibiotic is resistant to beta lactamases

Answer 23

Special note of Aztreonam

Question 24

* GI upset and rashes * Some occasional abnormal liver functions

Answer 24

ADR of Aztreonam

Question 24

2 TYPES OF Monobactams

Answer 24

1. Aztreonam 2. Tigemonam

Question 24

Newer monobactam that is resistant to beta lactamases

Answer 24

Tigemonam

Question 24

Tigemonam; Active against:

Answer 24

E.coli Klebsiella Proteus Citrobacter Serratia Enterobacter

Question 25

NOTE: Not active against Pseudomonas

Answer 25

Tigemonam

Question 26

* Kinetics: - Excellent Oral absorption

Answer 26

Tigemonam

Question 27

Consist of several structurally related but chemically distinct entities of amino acids - Thus polypeptide

Answer 27

Glycopeptides

Question 27

Refers to sugar/carbohydrate portion

Answer 27

“Glyco”

Question 27

Refers to the disulfide bonds between amino acids

Answer 27

“Peptide”

Question 28

MOA: Cell wall synthesis inhibitors

Answer 28

Glycopeptides

Question 29

NOTE: Do not contain the beta-lactam ring

Answer 29

Glycopeptides

Question 30

4 TYPES OF Glycopeptides

Answer 30

1. Vancomycin 2. Teicoplanin 3. Dalbavancin 4. Telavancin

Question 31

Vancomycin Source:____________

Answer 31

Streptomyces orientalis

Question 32

Prototype glycopeptide antibiotic

Answer 32

Glycopeptides

Question 32

Inhibition of the D-alanine-D-alanine cross linking of the NAM and NAG components of the bacterial cell wall

Answer 32

MOA of Glycopeptides

Question 32

Active only against: Gram-Positive (Narrow Spectrum)

Answer 32

Glycopeptides

Question 33

Can be given IV or PO

Answer 33

Glycopeptides

Question 34

Drug of Choice Against Methicillin-Resistant Staphylococcus aureus

Answer 34

Gram-Positive (Narrow Spectrum)

Question 35

* GI upset * Nephrotoxicity and Hepatotoxicity * REDMAN SYNDROME - Flushing Syndrome

Answer 35

ADR of Vancomycin

Question 36

Flushing Syndrome

Answer 36

REDMAN SYNDROME

Question 37

Other Glycopeptides "TDT"

Answer 37

Teicoplanin Dalbavancin Telavancin

Question 37

All are Derivatives of Vancomycin:

Answer 37

Teicoplanin Dalbavancin Telavancin

Question 38

Semi-synthetic antibiotics

Answer 38

Derivatives of Vancomycin

Question 38

Pharmacopore:

Answer 38

BETA-LACTAM RING