Cell Membrane Permeability

Question 1

What are the two classes of disruptors of cell membrane permeability?

Answer 1

1) Polypeptides

2) Cyclic Lipopeptides

Question 2

What two drugs are polypeptides?

Answer 2

polymyxins and gramicidins

Question 3

Are polymyxins acidic, basic, or neutral?

Answer 3

Basic

Question 4

Are gramicidins acidic, basic, or neutral?

Answer 4

Neutral

Question 5

Which type of bacterial cells do polypeptides act on?

Answer 5

gram-negative

Question 6

What type of bacterial cells do cyclic lipopeptides act on?

Answer 6

gram-positive

Question 7

How do polypeptides pass through the cell wall?

Answer 7

Porin channels

Question 8

Where do polypeptides attach to the cell membrane?

Answer 8

They can bind ionically to the cell membrane or to phospholipids on the outside of the membrane

Question 9

What happens to the membrane when polypeptides bind to the phospholipids on the outside of the membrane?

Answer 9

It contributes to the sensitivity of the polymyxins

Question 10

What do cyclic lipopeptides form a complex with?

Answer 10

Calcium

Question 11

What do the calcium/cyclic lipopeptide complexes do to the cell membrane of gram-positive cells?

Answer 11

They cause potassium to leave the cell causing rapid depolarization

Question 12

What is the consequence of rapid depolarization of the cell membrane?

Answer 12

The cell can’t produce proteins, DNA, or RNA

Question 13

What are the two mechanisms of resistance for polypeptides?

Answer 13

The gram-negative cell wall can prevent the antibiotic from entering, and the lipopolysaccharides can have their charge changed from negative to neutral

Question 14

Why are polypeptides rarely used systemically?

Answer 14

They are extremely neurotoxic and nephrotoxic

Question 15

What happens when you pair polypeptides with divalent cations?

Answer 15

It decreases the activity of the polypeptides

Question 16

Why are polypeptides administered parenterally?

Answer 16

Because there is very little absorption in the GI tract, and it doesn’t disperse well in the body

Question 17

What happens systemically when polypeptides are applied topically?

Answer 17

There is little systemic effect because of their affinity for cell membranes

Question 18

When using cyclic lipopeptides, there is an increased risk of ______. (An infection on top of another infection.)

Answer 18

Superinfection

Question 19

What other toxicity is associated with cyclic lipopeptides besides superinfection?

Answer 19

Cranial and peripheral neuropathy

Question 20

Besides forming complexes and depolarizing the cell membrane, what else do cyclic lipopeptides inhibit?

Answer 20

The formation of lipoteichoic acid

Question 21

With its unique action on gram-positive bacteria, what can cyclic lipopeptides be used to treat?

Answer 21

Gram-positive bacterial infections that are resistant to vancomycin, linezolid, and methicillin