Polymyxins

Question 1

Pharmacokinetics:

Answer 1

Absorption: Poor- not oral or topical.

Distribution: Poor- blood plasma is low because polymyxins bind to cell membranes as well as tissue debris and purulent exudates.

Metabolism:

Excretion: Kidney. T1/2 3-6 h.

Question 2

Mode of action:

Answer 2

Bactericidal.

Question 3

Mechanism of action:

Answer 3

Disrupt cell membrane (LPS) and disrupt the function and permeability.
Works on gram-.

Question 4

Spectrum:

Answer 4

Gram- bacilli.
Enterobacter, Klebsiella, Salmonella, Pastuerella, Bordetella, Shigella, E.Coli, Pseudomonas.

Topical: S. aureus.

Question 5

Chemistry:

Answer 5

Is a positive charge= attracted to -.
(Gram+ have thick wall and no outer membrane= don’t work.)

Polymyxins neutralize LPS.

Question 6

In case of E.coli:

Answer 6

Polymyxins kills E.coli fast -> endotoxins released -> endotoxaemia, that can kill!
Piglets are especially sensitive.

Question 7

Most used polymyxin in vet. med:

Answer 7

Polymyxin B, polymycin E= colistin
Polymyxin M

Used topically or PO.

Colistimethate is a form of colistin- parenteral admin.

Question 8

Polymyxin B:

Answer 8

Topical ointment in mixture with bacitracin or neomycin.

Synergistically when combined with: potentiated sulfonamides, tetracyclines, and penicillins, fluoroquinolones, aminoglycosides.

POTENT HISTAMINE RELEASER!

Question 9

Resistance:

Answer 9

Uncommon. <5%.

Chromosomal, plasmid encoded?

Question 10

Side effects:

Answer 10

Nephrotoxic -> tubular necrosis.
Neurotoxic.
Used mainly oral, opthalmic, otic or topical because of this.
Higher cc -> neuromuscular blockade.
Pain at injection site.
Polymyxin is a potent histamine releaser.

Question 11

Polymyxin Indication:

Answer 11

Parenteral: Lifethreatening infection gr-. Pseudomonas.
WP= 0 days. IV can be potentially toxic.

Oral: intestinal infection.

Topical: pyoderma, otitis extrena, intramammary,

Colistin: gr- mastitis in cow, endotoxins can kill cow fast.