Exam 1- Cushman Lec 4- Chloramphenicol + Quinolones Flashcards
What is the moa of chloramphenicol?
Binds reversibly to 50S ribosomal subunit
-inhibits peptidyl transferase activity of the ribosome and blocks peptide bond formation between P and A site
What is the therapeutic use of chloramphenicol?
Chloramphenicol sodium succinate is a prodrug for IV or IM administration
-bacterial meningitis, typhoid fever, rickettsial infection, intraocular infection
-can penetrate into brain
What is the solubility of chloramphenicol?
Lipid soluble, remains relatively unbound to plasma proteins
What are the resistance mechanisms against chloramphenicol?
-reduced membrane permeability
-mutation of 50S ribosomal subunit
-increased chloramphenicol acetyltransferase which acetylates the drug to form metabolites that do not bind the ribosome
How is chloramphenicol metabolized?
-To its inactive glucuronide in the liver that is excreted by the kidneys
–catalyzed by glucuronyl transferase
How does chloramphenicol metabolism affect dosing?
Needs dose reduction in liver impairment
What serious toxicity does chloramphenicol have?
Aplastic anemia
-generally fatal
-becomes apparent weeks or months after treatment is stopped
-need blood levels to be monitored
True or False: bone marrow suppression caused by chloramphenicol is a predictor of future development of aplastic anemia
False
What are the 1st generation quinolones?
Oxolinic acid
Nalidixic acid
What is the antibiotic activity of the first generation quinolones?
Activity against Gram -
Limited activity against Gram +
What are 1st generation quinolones used for?
*Do not achieve useful systemic concentrations
*Only treat lower UTIs
BOTH ARE DISCONTINUED
What antibiotic is a second-generation quinolone?
Ciprofloxacin
What structural components do second generation quinolones have?
Fluorine substituent at C-6
Heterocyclic ring at C-7
“fluoroquinoloes”
What is the antibiotic activity of second-generation quinolones?
Broader spectrum and more potent
Extended activity against Gram + and potent against Gram -
What is the most potent fluoroquinolone?
Ciprofloxacin
What are the third and fourth generation quinolones?
Levofloxacin
Moxifloxacin
Ozenoxacin
What is the activity of the 3rd and 4th quinolones?
Improved activity against Gram + organisms
*none are as potent as Ciprofloxacin against Gram -
Which quinolone is a drug of last resort?
Moxifloxacin
What is Ozenoxacin used to treat?
Impetigo
-topical since this is a skin rash
What is the function of topoisomerase I?
Cuts one strand of DNA to allow for untwisting
What is the function of topoisomerase II?
Cuts two DNA strands to allow for untwisting
DNA religation isblocked by what drug class?
Quinolones
