Cell Membrane Permeability Flashcards
What are the two classes of disruptors of cell membrane permeability?
1) Polypeptides
2) Cyclic Lipopeptides
What two drugs are polypeptides?
polymyxins and gramicidins
Are polymyxins acidic, basic, or neutral?
Basic
Are gramicidins acidic, basic, or neutral?
Neutral
Which type of bacterial cells do polypeptides act on?
gram-negative
What type of bacterial cells do cyclic lipopeptides act on?
gram-positive
How do polypeptides pass through the cell wall?
Porin channels
Where do polypeptides attach to the cell membrane?
They can bind ionically to the cell membrane or to phospholipids on the outside of the membrane
What happens to the membrane when polypeptides bind to the phospholipids on the outside of the membrane?
It contributes to the sensitivity of the polymyxins
What do cyclic lipopeptides form a complex with?
Calcium
What do the calcium/cyclic lipopeptide complexes do to the cell membrane of gram-positive cells?
They cause potassium to leave the cell causing rapid depolarization
What is the consequence of rapid depolarization of the cell membrane?
The cell can’t produce proteins, DNA, or RNA
What are the two mechanisms of resistance for polypeptides?
The gram-negative cell wall can prevent the antibiotic from entering, and the lipopolysaccharides can have their charge changed from negative to neutral
Why are polypeptides rarely used systemically?
They are extremely neurotoxic and nephrotoxic
What happens when you pair polypeptides with divalent cations?
It decreases the activity of the polypeptides
Why are polypeptides administered parenterally?
Because there is very little absorption in the GI tract, and it doesn’t disperse well in the body
What happens systemically when polypeptides are applied topically?
There is little systemic effect because of their affinity for cell membranes
When using cyclic lipopeptides, there is an increased risk of ______. (An infection on top of another infection.)
Superinfection
What other toxicity is associated with cyclic lipopeptides besides superinfection?
Cranial and peripheral neuropathy
Besides forming complexes and depolarizing the cell membrane, what else do cyclic lipopeptides inhibit?
The formation of lipoteichoic acid
With its unique action on gram-positive bacteria, what can cyclic lipopeptides be used to treat?
Gram-positive bacterial infections that are resistant to vancomycin, linezolid, and methicillin
