Disruptors of Cell Membrane permeability Flashcards
Name the polypeptides.
Polymixins (B, E and colistin) and gramicidin
What is the activity of polypeptides?
CIDAL
What is the MoA of polypeptides?
bind to phospholipids to penetrate the cell membrane, use porin channels to penetrate membrane in gram - cells, act as cationic detergents
What is the mechanism of resistance against polypeptides?
For gram (-) cells, some species may prevent access of polymixins to the cell membrne (proteus and serratia). Adding glycine to the Lipid A anchor of LPS molecules may change the charge of the surface to neutral. In vivo, greater presence of divalent cations like Ca2+ will decrease polymyxins by interfering with binding to the membrane
Describe the toxicity of the polypeptides.
Nephro and neurotoxicity. rarely used systemically due to toxicity (think most polymyxins are in ointments not absorbed by the skin)
What are polymixins NOT active against?
gram positive bacteria, gram negative cocci (mainly active against gram negative bacilli)
Polypeptides are not absorbed where?
the GIT, do not cross placenta, do not cross aqueous humor of the eye or snyovial fluid
Name the cyclic lipopeptides.
Daptomycin
What is the activity of daptomycin?
CIDAL
Describe the MoA of daptomycin
has membrane-seeking behavior similar to polymyxins, but MoA is unique - inhibits biosynthesis of lipoteichoic acid, a component of the cell wall of gram + bacteria. It forms complexes with calcium that bind to bacterial cell membranes and cause a rapid loss of intracellular potassium
What is the mechanism of resistance for daptomycin?
It retains potency against gram + bacteria resistant to other antibiotics because of its unique mechanism of action
What is the toxicity for daptomycin?
superinfection, cranial or peripheral neuropathy
What is daptomycin indicated for?
serious gram positive infection only - administered parenterally
