Aminoglycosides & Broad Spectrum Antibiotics Flashcards
mechanism of aminoglycosides?
- targets protein synthesis (targets 30S) - irreversibly inhibits protein synthesis of susceptible microorganisms by inhibiting functioning of 30S subunit
- blocks initiation of translation and causes the misreading of mRNA
“All aminoglycosides are usually used ________”
“All amino glycosides are usually used IN COMBINATION.”
list of aminoglycosides
- streptomycin - TB second line agent (now more first line), IV/IM
- gentamycin - G-, combo - IV/IM, topical
- tobramycin - G-, combo - IV/IM, topical
- amikacin - G-, combo - IV/IM
- neomycin - oral, topical
characteristics of aminoglycosides
- contain amino sugars in glycosidic linkage
- polycations
- POLARITY RESPONSIBLE FOR PHARMOKINETIC PROPERTIES
- BACTERICIDAL (used in combo w/ PCN)
- to be effective must be transported into susceptible bacteria (req O2) and bind to 30S subunit to produce non-functional 30S initiation complex
- under aerobic conditions = BACTERICIDAL
- not effective in anaerobes
when are aminoglycosides used?
to treat infection caused by susceptible AEROBIC G- ENTERIC BACTERIA (rods) (usu combined w/ beta-lactam antibiotics), or when suspicion of SEPSIS or ENDOCARDITIS
when is streptomycin used?
- tularemia (francisella tularensis)
- bubonic plague (yersinia pestis)
- TB
- endocarditis when w/ other agents in combo therapy
when is gentamycin/tobramycin/emikacin used?
against P. aeruginosa
when is neomycin/gentamycin used?
topical application of wounds & burns caused by gram neg organisms
What is the recommendation for infections due to Enterococci?
- two synergistic antibiotics
- rec therapy = gentamycin or streptomycin + vancomycin or a b-lactam (such as PCN)
DOC for Gram + cocci (enterococci species)?
aminoglycoside + PCN
DOC for tularemia? (rabbit fever)
gentamycin
DOC for pseudomonas aeruginosa?
aminoglycoside + antipseudomonal PCN
tobramycin + piperacillin/ticarcillin
amino glycosides are CONCENTRATION DEPENDENT KILLING. what does this mean?
increasing concentrations kill an increasing population of bacteria and at a more rapid rate
aminoglycosides have a significant POST-ANTIBIOTIC EFFECT - explain
- antibacterial activity persists beyond time that antibiotic is measurable
- single large dose has better efficacy than multiple smaller doses - reduces toxic side effects
toxicity of aminoglycosides
- OTOTOXICITY
- NEPHROTOXICITY
- overgrowth of non-susceptible organism
- GI upset
- neuromuscular weakness
- nausea, vomiting
- allergy
- diarrhea
toxicity of loop diuretics (ethacrynic acid, furosemide)? (usu given at same time as aminoglycoside)
- OTOTOXICITY
toxicity of vancomycin, cephalosporins, cisplatin, cidofovir?
- NEPHROTOXICITY
pharmokinetics of aminoglycosides
- IM or IV or topical
- none absorbed adequately after oral admin (not absorbed through GI tract; 3% for neomycin)
- none penetrates CSF readily
- normal kidney rapidly excretes all
mechanism of action chloramphenicol
reversibly binds to 50S subunit of bacterial 70S ribosomes and prevents attachment of amino acid containing end of aminoacyl-tRNA to acceptor sire on ribosome
- inhibits protein synthesis
- BACTERIOSTATIC
- can be bactericidal against H.flu, Neisseria mening, strep pneu at therapeutic concentrations
- can INHIBIT MITOCHONDRIAL PROTEIN SYNTHESIS IN MAMMALIAN CELLS
resistance of aminoglycosides?
- deficiency of ribosomal receptors (if it can’t bind, can’t have effect)
- lack of permeability of drug molecule into bacteria
- enzymatic modification by bacteria
*** aminoglycosides usu used in COMBO w/ other antibiotics
3 classes of BROAD SPECTRUM ANTIBIOTICS?
- chloramphenicol
- tetracyclines
- glycylcyclines
characteristics CHLORAMPHENICOL (chloromycetin)
- broad spectrum
- first/prob only successful synthetic antibiotic
- associated w/ FATAL APLASTIC ANEMIA and other serious/fatal side effects (used when no other options available)
toxicities of chloramphenicol
- dose dependent (bone marrow suppression) - anemia, leukopenia, thrombocytopenia, reversible upon discontinuation of drug
- dose independent (fatal aplastic anemia = rare)
- GRAY BABY SYNDROME in infants - inadequate activity of glucoronyl transferase in newborn liver
- rash, angioedema, urticaria
- rarely anaphylactic rxns
chloramphenicol resistance
- acetyl transferase acetylates and inactivates chloramphenicol
- efflux pumps
