Tetracyclines, chloramphenicol, macrolides/ketolides, aminoglycosides, nitromidazoles Flashcards
Tetracyclines, chloramphenicol, macrolides
MOA - 30s or 50s – protein synth inhibitors
Active against fungi
Dairy, Al, Na, Ca impair absorption
All pass BBB (mino and doxy pass best)
Renal excretion
SE - GI, stomatitis, glossitis (like sulfa), photosensitivity, onycholysis, hepatotoxic, prego after 4th month due to Ca complexes, superinfections (candida)
Tetracycline
MOA - 30s inhibitor
Resistance - decreases number of porins, MDR, ribosome protection, mutations
Broad spec
TX for acne vulgaris
Not used often due to resistance
Doxycycline
Passes BBB
Less GI irritation - can be taken with food
Safest for renal
Preferred over mino due to mino tox
More phototoxicity
Minocycline
Passes BBB
Minocycline-associated vestibular toxicity - dizziness, n/v, vertigo, post first dose
Tigecycline
Broader spec with less resistance
Not as susceptible to ribosome protection protein or MDR
Only IV
Good alternative for MRSA or VRE
Chloramphenicol
MOA - 50s
Broad spec – Good BBB
SE - very serious so only reserved for meningitis, rickets
- Causes gray baby syndrome w/i 48 hours of initiation
- BM tox
Macrolides
Erythromycin, azithromycin, clarithromycin, telithromycin (ketolide)
All are bacteriostatic 50s
Not good for CNS
Resistance - esterases, methylases (unique)
Erythromycin
Macrolide
Acid labile
Crosses placenta and milk
SE - GI – stimulates GI motility by acting on motilin receptors and promotes peristalsis
-QT
DDI - strong 3A4 inhibitor
Azithromycin
Macrolide
Methyl-substituted nitrogen - increases acid stability, tissue penetration, expands spec
Does not cross BBB
SE - less than erithro
DDI - DOES NOT INHIBIT 3A4
PK - very long t1/2 – QDay dosing
Clarithromycin
Macrolide
More active against gram + and less against gram - than azithromycin
DDI - STRONG 3A4 LIKE ERYTHRO
Telithromycin
Ketolide (AMD)
Broad spec and not sensitive to MDR or methylase
SE - severe hepatotox, QT
DDI - strong 3A4
Aminoglycosides
Highly effective against gram -
-used for nosocomial infections, esp in HIV
MOA - binds to 30s
-blocks protein synth, prevents translation, and inserts wrong AA into site
Use - serious aerobic gram -
-ineffective against anaerobic
Resistance - acetylation, phosphorylation, adenylation
-amikacin is less susceptible
PK - IV only, poor CNS
-Renal excretion
Combo Tx - broadens spec and avoids resistance
DDI - PCN inactivated by aminoglycosides
Metronidazole and tinidazole
MOA - metro is a prodrug activated by reduction of nitro group – creates radicals
-recycled by ferredoxin created by pyruvate decarboxylation
Tinidazole - as effective as metro, with longer t1/2
Resistance - decreased ability to activate
-allows oxygen to build up which prevents recycling
TX - anaerobic
PK - BBB penetration but not placenta
-hepatic
SE - TEN/SJS, disulfiram-like rxn
