Exam 2: Inhibitors Of Protein Synthesis 2 Flashcards
(43 cards)
What are the 5 aminoglycoside drugs?
Streptomycin, gentamicin, tobramycin, Amikacin, and Neomycin
What is the MOA for Aminoglycosides?
Irreversibly inhibit protein synthesis of susceptible microorganisms by inhibiting the function of 30s subunit.
Bactericidal- hits 3 different parts of the translation machinery
Why aren’t aminoglycosides effective against anaerobic species?
In order to be effective, aminoglycosides first must be actively transported (OXYGEN REQUIRING) into the bacteria and bind to the 30s subunit
What are Aminoglycosides used to treat?
Aerobic G- enteric bacteria or when there is suspicion of sepsis or endocarditis
Which aminoglycosides are effective against P. Aeruginosa?
Gentamicin, tobramycin, and amikacin.
What are the significant toxicities associated with aminoglycosides?
Ototoxicity and nephrotoxicity.
-Dependent on duration of time the concentration of the drug is above threshold.
Are Aminoglycosides have time or concentration dependent killing?
Concentration dependent killing.
Do aminoglycosides have. High or low post antibiotic effect and what does this mean for dosage?
High PAE.
A single large dose has better efficacy than multiple smaller doses which also reduces the toxic side effects.
How are aminoglycosides administed?
IM, IV, or topical
What are the methods of resistance for aminoglycosides?
- Deficiency of ribosomal receptors
- Lack of permeability of the drug molecule into the bacteria
- Enzymatic modification by the bacteria
Do Aminoglycosides have cross resistance?
Bacteria that acquire resistance to one aminoglycoside may exhibit cross resistance to other aminoglycosides.
What type of antibiotic is chloramphenicol?
Broad spectrum
What is the significant side effect associated with chloramphenicol?
Fatal aplastic anemia
What is the MOA of chloramphenicol?
Reversibly binds to the 50s subunit and prevents the attachment of the amino acid containing end of the aminoacyl tRNA to the acceptor site on the ribosome.
Is Chloramphenicol bacteriostatic or -cidal?
Bacteriostatic, but can b bacteriocidal against certain common meningeal pathogens such as H. Influenzae, N. Meningitis, and strep pneumoniae at therapeutic concentrations
What does chloramphenicol also inhibit in mammalian cells and what can this lead to?
It can inhibit mitochondrial protein synthesis.
Many of the adverse side effects such as bone marrow depression and gray baby syndrome appear to be a result of this.
What is the spectrum of chloramphenicol?
G-, G+, anaerobes, aerobes, atypicals (spirochetes, rickettsial, and chlamydiae.
What is the therapeutic use of Chloramphenicol?
NOT FIRST CHOICE and restricted to life threatening infections.
-Typhoid fever, meningitis, ricketsia, bacterial conjunctivitis (topical)
What is Chloramphenicol an inhibitor of?
Potent inhibitor of CYP34A and CYP2C19
How is Chloramphenicol metabolized?
In the liver, conjugated with glucuronic acid to form chloramphenicol glucurnate, an inactive metabolite, which is then excreted in the kidney.
Which drug has the best CNS penetration?
Chloramphenicol
What are the hematopoietic problems that can arise from Chloramphenicol use?
- Bone marrow depression (dose dependent and reversible upon discontinuation)
- Fatal aplastic anemia (dose independent and can develop months after drug has been discontinued)
Why is chloramphenical not recommended for babies?
They can develop gray baby syndrome from inadequate activity of glucuronyl transferase in newborn liver. Discontinuation at onset can lead to recovery- if not taken off they will die.
How can resistance to chloramphenicol occur?
- Acetyl transferase produced by the resistant organism acetylates and inactivates chloramphenicol.
- Binding site may be modified
- Efflux pumps
