Polymyxins
Polymyxins are a group of polypeptide antibiotics that were first obtained in 1947 from strains of Bacillus polymyxa . Similar to the cell membrane , they have a polarity . As a result, they are stored in the cell membrane of gram-negative bacteria and disrupt their permeability . Because of this, these antibiotics have a bactericidal effect, but only against germs localized outside the body cells (extracellular). To polymyxins including polymyxin B and the first time in 1950 by Shizuo Kayama from culture of Bacillus colistinus gained colistin (polymyxin E =).
When used parenterally , polymyxins can develop toxic side effects, particularly in relation to the nervous system ( neurotoxicity ) and the kidneys ( nephrotoxicity ). They are contraindicated in kidney failure . In human medicine , colistin preparations are therefore used parenterally in the form of a better tolerated prodrug colistimethate sodium (CMS). When colistin preparations are used orally, there is no relevant absorption in the intestine .
Polymyxins are considered reserve antibiotics .
structure
Polymyxins are branched, cyclic polypeptides and consist of ten peptides (decapeptide). At the N terminus they have a 6-methyl-octanoic acid , which, as a fatty acid, realizes the lipophilic part of the molecule. In contrast, there is a cation-active, hydrophilic area. Polymyxins therefore have a polar structure and are surface-active.
Polymyxin B differs from colistin A only in the exchange of a single amino acid . While polymyxin B has a D- phenylalanine in the ring, colistin A has a D-leucine .
literature
- Löscher et al. (Ed.): Pharmacotherapy in pets and farm animals . Paul Parey Verlag, 7th edition 2006, p. 266, ISBN 3-8304-4160-6 .
- Karl Wurm, AM Walter: Infectious Diseases. In: Ludwig Heilmeyer (ed.): Textbook of internal medicine. Springer-Verlag, Berlin / Göttingen / Heidelberg 1955; 2nd edition, ibid. 1961, pp. 9–223, here: p. 55.
Individual evidence
- ↑ a b c Schubert-Zsilavecz, Manfred., Roth, Hermann J .: Medicinal Chemistry: Targets - Drugs - Chemical Biology; 191 tables . 2., completely reworked. and exp. Ed. Dt. Apotheker-Verl, Stuttgart 2010, ISBN 978-3-7692-5002-2 .