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Polymyxin B
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| Systematic (IUPAC) name |
| N-[4-amino-1-[[1-[[4-amino-1-oxo-1-[[6,9,18-tris (2-aminoethyl)-15-benzyl-3-(1-hydroxyethyl)-12- (2-methylpropyl)-2,5,8,11,14,17,20- heptaoxo-1,4,7,10,13,16,19-heptazacyclotricos-21-yl] amino]butan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl] amino]-1-oxobutan-2-yl]-6-methyloctanamide |
| Identifiers |
| CAS number |
1405-20-5 |
| ATC code |
A07AA05 J01XB02 S01AA18 S02AA11 S03AA03 QJ51XB02 |
| PubChem |
CID 5702105 |
| DrugBank |
APRD01190 |
| Chemical data |
| Formula |
C56H100N16O17S |
| Mol. mass |
1301.56 g/mol |
| Therapeutic considerations |
| Pregnancy cat. |
? |
| Legal status |
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| Routes |
Topical |
Polymyxin B is an antibiotic primarily used for resistant gram-negative infections. Polymyxins bind to the cell membrane and alter its structure making it more permeable. The resulting water uptake leads to cell death. They are cationic, basic proteins that act like detergents (surfactants). Side-effects include neurotoxicity and acute renal tubular necrosis. It is commonly used in the topical first-aid preparation Neosporin.
- Family of polypeptides with attached fatty acid; cationic detergent at physiological pH, both hydrophilic and hydrophobic properties
- Bactericidal for gram-negative; little to no effect on gram-positive since cell wall is too thick to permit access to membrane
Mechanism of action
- Alters bacterial outer membrane permeability by binding to a negatively charged site in the lipopolysaccharide layer, which has an electrostatic attraction for the positively charged amino groups in the cyclic peptide portion (this site normally is a binding site for calcium and magnesium counter ions); the result is a destabilized outer membrane
- Fatty acid portion dissolves in hydrophobic region of cytoplasmic membrane and disrupts membrane integrity
- Leakage of cellular molecules, inhibition of cellular respiration
- Binds and inactivates endotoxin1
- Relative absence of selective toxicity: nonspecific for cell membranes of any type, highly toxic
Research application
- In addition to its antibiotic function, polymix B has been used to clear endotoxin contamination in reagents.
References
- ^ Cardoso LS, Araujo MI, Góes AM, Pacífico LG, Oliveira RR, Oliveira SC (2007). "Polymyxin B as inhibitor of LPS contamination of Schistosoma mansoni recombinant proteins in human cytokine analysis". Microb. Cell Fact. 6: 1. doi:10.1186/1475-2859-6-1. PMID 17201926. PMC 1766364. http://www.microbialcellfactories.com/content/6//1.
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Antibacterials: cell envelope antibiotics (J01C-J01D) |
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Internal to membrane/
(inhibit peptidoglycan subunit
synthesis and transport) |
NAM synthesis inhibition (Fosfomycin) · DADAL/AR inhibitors (Cycloserine) · bactoprenol inhibitors (Bacitracin)
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Glycopeptide/
(inhibit PG chain elongation) |
Vancomycin# (Oritavancin, Telavancin) · Teicoplanin (Dalbavancin) · Ramoplanin
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β-lactams/
(inhibit cross-links
with PBP) |
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Penicillins/
(penams)
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Extended sp.
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aminopenicillins: Amoxicillin# · Ampicillin# (Pivampicillin, Hetacillin, Bacampicillin, Metampicillin, Talampicillin) · Epicillin
carboxypenicillins: Carbenicillin (Carindacillin) · Ticarcillin · Temocillin
ureidopenicillins: Azlocillin · Piperacillin · Mezlocillin
other: Mecillinam (Pivmecillinam) · Sulbenicillin
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Narrow sp.
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β-lactamase sensitive
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Benzylpenicillin (G)#: Clometocillin · Benzathine benzylpenicillin# · Procaine benzylpenicillin# · Azidocillin · Penamecillin
Phenoxymethylpenicillin (V) #: Propicillin · Benzathine phenoxymethylpenicillin · Pheneticillin
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β-lactamase resistant
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Cloxacillin# (Dicloxacillin, Flucloxacillin) · Oxacillin · Meticillin · Nafcillin
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Penems
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Faropenem
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Carbapenems
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Biapenem · Doripenem · Ertapenem · Imipenem · Meropenem · Panipenem
|
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Cephalosporins/
(cephems)
|
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1st (PEcK)
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Cefazolin# · Cefacetrile · Cefadroxil · Cefalexin · Cefaloglycin · Cefalonium · Cefaloridine · Cefalotin · Cefapirin · Cefatrizine · Cefazedone · Cefazaflur · Cefradine · Cefroxadine · Ceftezole
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2nd (HEN)
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Cefaclor · Cefamandole · Cefminox · Cefonicid · Ceforanide · Cefotiam · Cefprozil · Cefbuperazone · Cefuroxime · Cefuzonam · cephamycin (Cefoxitin, Cefotetan, Cefmetazole) · carbacephem (Loracarbef)
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3rd
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Cefixime# · Ceftazidime# · Ceftriaxone# · Cefcapene · Cefdaloxime · Cefdinir · Cefditoren · Cefetamet · Cefmenoxime · Cefodizime · Cefoperazone · Cefotaxime · Cefpimizole · Cefpiramide · Cefpodoxime · Cefsulodin · Cefteram · Ceftibuten · Ceftiolene · Ceftizoxime · oxacephem (Flomoxef, Latamoxef ‡)
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4th
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Cefepime · Cefozopran · Cefpirome · Cefquinome
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5th
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Ceftobiprole · Ceftaroline
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Veterinary
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Ceftiofur · Cefquinome · Cefovecin
|
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Monobactams
|
Aztreonam · Tigemonam · Carumonam
|
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β-lactamase inhibitors
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penam (Sulbactam, Tazobactam) · clavam (Clavulanic acid)
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Combinations
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Co-amoxiclav (Amoxicillin/clavulanic acid)# · Imipenem/cilastatin# · Ampicillin/sulbactam (Sultamicillin) · Piperacillin/tazobactam
|
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| Other |
polymyxins/detergent (Colistin, Polymyxin B) · depolarizing (Daptomycin) · hydrolyze NAM-NAG (Lysozyme)
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#WHO-EM. ‡Withdrawn from market. Clinical trials: †Phase III. §Never to phase III
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gr+f/gr+a(t)/gr-p(c)/gr-o
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Antidiarrheals, intestinal anti-inflammatory/anti-infective agents (A07) |
|
| Intestinal anti-infectives |
Antibiotics (Neomycin, Nystatin, Natamycin, Streptomycin, Polymyxin B, Paromomycin, Amphotericin B, Kanamycin, Vancomycin, Colistin, Rifaximin)
Sulfonamides (Phthalylsulfathiazole, Sulfaguanidine, Succinylsulfathiazole)
Nitrofuran (Nifuroxazide, Nifurzide)
Imidazole (Miconazole)
Arsenical (Acetarsol)
Oxyquinoline (Broxyquinoline)
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| Intestinal adsorbents |
Charcoal · Bismuth · Pectin · Kaolin · Crospovidone · Attapulgite · Diosmectite
|
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| Antipropulsives (opioids) |
Opium (Laudanum) · Codeine · Morphine (Paregoric)
crosses BBB: Diphenoxylate · Difenoxin
does not cross BBB: Loperamide
|
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| Intestinal anti-inflammatory agents |
corticosteroids acting locally (Prednisolone, Hydrocortisone, Prednisone, Betamethasone, Tixocortol, Budesonide, Beclometasone)
antiallergic agents, excluding corticosteroids (Cromoglicic acid)
aminosalicylic acid and similar agents (Sulfasalazine, Mesalazine, Olsalazine, Balsalazide)
|
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| Antidiarrheal micro-organisms |
Saccharomyces boulardii
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| Other antidiarrheals |
Albumin tannate · Ceratonia · Octreotide · Racecadotril
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anat(t, g, p)/phys/devp/cell
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noco/cong/tumr, sysi/epon
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proc, drug(A2A/2B/3/4/5/6/7/14/16)
|
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Otologicals (S02) |
|
| Anti-infectives |
Acetic acid • Aluminium acetotartrate • Boric acid • Chloramphenicol • Chlorhexidine • Ciprofloxacin • Clioquinol • Gentamicin • Hydrogen peroxide • Miconazole • Neomycin • Nitrofurazone • Ofloxacin • Polymyxin B • Rifamycin • Tetracycline
|
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| Corticosteroids |
Betamethasone • Dexamethasone • Fluocinolone acetonide • Hydrocortisone • Prednisolone
|
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| Analgesics and anesthetics |
Lidocaine • Cocaine • Phenazone
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