Exam 1- Cushman Lec 4- Chloramphenicol + Quinolones

Question 1

What is the moa of chloramphenicol?

Answer 1

Binds reversibly to 50S ribosomal subunit

-inhibits peptidyl transferase activity of the ribosome and blocks peptide bond formation between P and A site

Question 2

What is the therapeutic use of chloramphenicol?

Answer 2

Chloramphenicol sodium succinate is a prodrug for IV or IM administration

-bacterial meningitis, typhoid fever, rickettsial infection, intraocular infection
-can penetrate into brain

Question 3

What is the solubility of chloramphenicol?

Answer 3

Lipid soluble, remains relatively unbound to plasma proteins

Question 4

What are the resistance mechanisms against chloramphenicol?

Answer 4

-reduced membrane permeability

-mutation of 50S ribosomal subunit

-increased chloramphenicol acetyltransferase which acetylates the drug to form metabolites that do not bind the ribosome

Question 5

How is chloramphenicol metabolized?

Answer 5

-To its inactive glucuronide in the liver that is excreted by the kidneys
–catalyzed by glucuronyl transferase

Question 6

How does chloramphenicol metabolism affect dosing?

Answer 6

Needs dose reduction in liver impairment

Question 7

What serious toxicity does chloramphenicol have?

Answer 7

Aplastic anemia
-generally fatal

-becomes apparent weeks or months after treatment is stopped
-need blood levels to be monitored

Question 8

True or False: bone marrow suppression caused by chloramphenicol is a predictor of future development of aplastic anemia

Answer 8

False

Question 9

What are the 1st generation quinolones?

Answer 9

Oxolinic acid
Nalidixic acid

Question 10

What is the antibiotic activity of the first generation quinolones?

Answer 10

Activity against Gram -

Limited activity against Gram +

Question 11

What are 1st generation quinolones used for?

Answer 11

*Do not achieve useful systemic concentrations

*Only treat lower UTIs

BOTH ARE DISCONTINUED

Question 12

What antibiotic is a second-generation quinolone?

Answer 12

Ciprofloxacin

Question 13

What structural components do second generation quinolones have?

Answer 13

Fluorine substituent at C-6
Heterocyclic ring at C-7

“fluoroquinoloes”

Question 14

What is the antibiotic activity of second-generation quinolones?

Answer 14

Broader spectrum and more potent

Extended activity against Gram + and potent against Gram -

Question 15

What is the most potent fluoroquinolone?

Answer 15

Ciprofloxacin

Question 16

What are the third and fourth generation quinolones?

Answer 16

Levofloxacin
Moxifloxacin
Ozenoxacin

Question 17

What is the activity of the 3rd and 4th quinolones?

Answer 17

Improved activity against Gram + organisms
*none are as potent as Ciprofloxacin against Gram -

Question 18

Which quinolone is a drug of last resort?

Answer 18

Moxifloxacin

Question 19

What is Ozenoxacin used to treat?

Answer 19

Impetigo
-topical since this is a skin rash

Question 20

What is the function of topoisomerase I?

Answer 20

Cuts one strand of DNA to allow for untwisting

Question 21

What is the function of topoisomerase II?

Answer 21

Cuts two DNA strands to allow for untwisting

Question 22

DNA religation isblocked by what drug class?

Answer 22

Quinolones