Polymyxins Flashcards
Pharmacokinetics:
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.
Mode of action:
Bactericidal.
Mechanism of action:
Disrupt cell membrane (LPS) and disrupt the function and permeability.
Works on gram-.
Spectrum:
Gram- bacilli.
Enterobacter, Klebsiella, Salmonella, Pastuerella, Bordetella, Shigella, E.Coli, Pseudomonas.
Topical: S. aureus.
Chemistry:
Is a positive charge= attracted to -.
(Gram+ have thick wall and no outer membrane= don’t work.)
Polymyxins neutralize LPS.
In case of E.coli:
Polymyxins kills E.coli fast -> endotoxins released -> endotoxaemia, that can kill!
Piglets are especially sensitive.
Most used polymyxin in vet. med:
Polymyxin B, polymycin E= colistin
Polymyxin M
Used topically or PO.
Colistimethate is a form of colistin- parenteral admin.
Polymyxin B:
Topical ointment in mixture with bacitracin or neomycin.
Synergistically when combined with: potentiated sulfonamides, tetracyclines, and penicillins, fluoroquinolones, aminoglycosides.
POTENT HISTAMINE RELEASER!
Resistance:
Uncommon. <5%.
Chromosomal, plasmid encoded?
Side effects:
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.
Polymyxin Indication:
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.