Lecture 8.1: Streptogramin & Oxazolidinone

Question 1

What are the Antibiotics that are used in the “Streptogramin”?

Answer 1

• Quinupristin &
• Dalfopristin

Question 2

What are the Names of these two structures?

Answer 2

Left: Quinupristin
Right: Dalfopristin

Question 3

What are the atoms within Quinupristin and Dalfopristin that allow salt formation and enhance water solubility?

Answer 3

• Q: Furthest Ring sturcture
• D: Lowest N- sturcture

Question 4

What is the way that Strptogramin, Quinupristim and Dalfopristin are Bactericidal compared to Bacteriostatic?

Answer 4

• Q & D: alone are Bacteriostatic
• Strepto: together are Bactericidal

Bacteriostatic = Enterococcus
Bactericidal = MRSA & MSSA

Question 5

What is the route of administration for Quinupristin - Dalfopristin?

Answer 5

• Parenteral but could be orally

Question 6

What is the Mechanism of Action for Dalfopristin alone?

Answer 6

• Interferes with the Peptidyl catalyzed step; inhibits peptidyl transferase
• Blocks Binding

Question 7

What is the Mechanism of Action for Quinupristin alone?>

Answer 7

• Binds to the Ribosomal Tunnel Blocking it

Question 8

What are the Theraputic Uses of Quinupristin - Dalfopristin?

Answer 8

• Enterococcus faecium [VRE]
• MRSA
• VRE UTI

Question 9

What is the most common resistance mechanism toward Quinupristin alone?

Answer 9

• Adenine methylation of A2058 in the 23s rRNA
• Maybe efflux pumps, Animal Feeds

Question 10

What are the main side effects of Quinupristin - Daflopristin?

Answer 10

• Inflammation, Pain, Nausea, Diarrhea, Rash

Question 11

What are the Pharmacokinetics of Quinupristin - Dalfopritin?

Answer 11

• Half Life is 1.5 h
• Transported into tissues [NOT BBB]
• Elimination: Poo & Pee

Question 12

What are the potential drug interaction for Quinupristin - Dalfopristin and the mechanisms invovled?

Answer 12

• Inhibited by CYP 3A4

Question 13

What is this sturture?

Answer 13

• Linezolid

Question 14

What is the Mechanism of action for Linezoild?

Answer 14

• Inhibits 70s formation by binding to 23s RNA on the 50s subunit; blocking 30s binding to 50s

Question 15

What are the theraputics uses of Linezolid?

Answer 15

• VRE [Enterococcus Faecium]
• Nosocomal MRSA
• Skin infections from MRSA

Question 16

What is the reason that Linezolid should only be used to trat drug-resistant Gram (+) bacteria?

Answer 16

• Reduce the bacteria that may become resistanct toward it???

Question 17

What is the mechanism of resistance for Linezolid?

Answer 17

• Targer Site Modifications; G to U Substitution reduced affinity to 50s

Question 18

What are the side effects of Linezolid?

Answer 18

• GI issues [N, V, D] Headache, Thrush, Thrombocytompenia, Myelosuppression…

Question 19

What is the metabolic pathway for Linezolid?

Answer 19

• By Morpholoine Ring Oxidation
• Excreted in the Urine

Question 20

What are the Pharmacokinetics and route of administration of Linezolid?

Answer 20

• 100% bioavailable orally with a half life of 4-6 h
• Orally or IV

Question 21

What are the potental drug interactions with Linezolid?

Answer 21

• Inhibitor of Monoamine Oxidase [Increases BP]

Question 22

What are some of the difference between Tedizolid and Linezolid?

Answer 22

• More potent to MRSA
• Prodrug [Tedizolid Phosphate]