Dr. Roane Tetracyclines EX 2 Flashcards
What are the 7 classes whose MOA is to disrupt protein synthesis?
-Tetracyclines
-Aminoglycosides
-Macrolides
-Chloramphenicol
-Clindamycin (lincosamide antibiotic)
-Quinupristin
-Linezolid
Spectrum of Activity
-gram (+)
-thick-borne pathogens (Rickettsia rickettsii, Borrelia burgdorferi)
-atypical pathogens
What does the black box warning for Tigecycline?
It should be reserved for use in situations when alternative treatments are not available
What are Gl
-Minocycline derivated
-fe Tigecycline
N,N-dimethylglycylamido side chain to position 9 of minocycline
MOA Tetracycline
-Block the binding of the aminoacyl-tRNA at the
“A” site
-Bacteriostatic (all protein inhibitors are static except of Aminoglycosides)
What are the resistance mechanisms against Tetracyclines?
-“R” factor - A plasmid gene for an efflux pump – TetA gene
-RRP’s (ribosomal resistance proteins) that block tetracycline binding to the active site
ADME of Tetracycline
-Absorption is OK but incomplete
-Milk and other diary products strongly interfere
ADME Distribution Tetracycline
Penetrates tissues well -> also in breast milk -> infants exposed
-bind to bones and teeth
-discoloring in teeth (CDC approved use in age under 8 - no teeth coloring)
-may inhibit bone growth
-Pregnancy Category D (risks outweigh benefits - give only if necessary)
ADME Metabolism
-Some are not metabolized
-Concentrate in the liver and bile -> extends the half-life
Why is the absorption of tetracyclines low with milk?
Chelation with Mg2+ or other divalent or trivalent cations
Adverse effects
-Nausea and diarrhea
-Esophageal irritation – take with water, standing
up, if possible
-Phototoxicity – sensitivity to sun
How is Tigecycline different from other Tetracyclines?
-glycylcycline tetracycline
-binds 30S subunit more strongly
-Less affected by the efflux pump resistance
-Broad spectrum
-IV only
What are the resistance overcome by newer Tetracyclines?
Eravacycline (Xerava): MRSA, VRE, CRE
Omadacycline (Nuzyra): RRP ribosomal resistance proteins - blocks tetracycline from binding to the A-site
Chloramphenicol
-inhibits peptidyltransferase
-Bacteriostatic, or bacteriocidal depending on the organism
-IV only
activity against some Rickettsial diseases (not first choice)
What is Chloramphenicol used for?
-Used in veterinary medicine
-Reserved use due to toxicity (bone marrow
suppression) - fatal aplastic anemia
-Also causes “Gray baby syndrome”: Anemia, cyanotic, limp, vomiting, hypotensive, ashen skin; can be fatal
-Rocky Mountain spotted fever (a Rickettsial disease)
– Brucellosis (a zoonotic)
– Tularemia (rabbit fever)
NOT FIRST CHOICE
