Cell Membrane Labilizer Part 3

Polymyxins have what spectrum of activity?

Narrow spectrum.

Polymyxins are primarily active against

Gram-negative bacteria.

Examples of bacteria susceptible to polymyxins

Enterobacter, Klebsiella, Salmonella, Pasteurella, Bordetella, Shigella, Pseudomonas, and Escherichia coli.

Most important pathogen targeted by polymyxins

Pseudomonas aeruginosa.

Polymyxins are effective against

Escherichia coli.

Polymyxins are effective against

Salmonella spp.

Polymyxins are effective against

Pasteurella spp.

Polymyxins are effective against

Bordetella spp.

Polymyxins are effective against

Klebsiella spp.

Polymyxins are effective against

Shigella spp.

Bacteria inherently resistant to polymyxins

Proteus spp. and Serratia spp.

Why Proteus and Serratia are resistant

Intrinsic resistance to polymyxin activity.

Major veterinary use of polymyxins

Oral treatment of E. coli diarrhea.

Major veterinary use of polymyxins

Oral treatment of Salmonella diarrhea.

Common topical use of polymyxins

Otitis externa caused by Pseudomonas.

Common topical use of polymyxins

Superficial lip infections.

Polymyxins are often used locally because

Systemic toxicity limits their use.

Polymyxins are poorly absorbed from

The gastrointestinal tract.

Polymyxins are poorly absorbed through

Skin and mucous membranes.

Absorption of polymyxins is rapid after

IM and SC administration.

Distribution of polymyxins

Largely confined to extracellular fluid.

Polymyxins do not readily enter

The cerebrospinal fluid.

Polymyxins accumulate in

Kidney, liver, lung, heart, and skeletal muscle.

Major route of elimination of polymyxins

Renal elimination.

Polymyxins are excreted mostly as

Degradation products.

Poor CSF penetration of polymyxins limits their use in

CNS infections.

Most important pharmacokinetic limitation of polymyxins

Poor absorption and poor CSF penetration.

Polymyxins act synergistically with

Tetracyclines.

Polymyxins act synergistically with

Chloramphenicol.

Polymyxins act synergistically with

Sulfamethoxazole.

Polymyxins act synergistically with

Carbenicillin.

Synergistic use of polymyxins is especially important against

Pseudomonas aeruginosa.

Polymyxins act synergistically with

Potentiated sulfonamides.

Additional benefit of polymyxins in endotoxemia

Reduction of endotoxin activity.

Antibacterial activity of polymyxins is decreased by

Pus.

Antibacterial activity of polymyxins is decreased by

Purulent exudate.

Antibacterial activity of polymyxins is decreased by

Debris.

Antibacterial activity of polymyxins is decreased by

Divalent cations.

Examples of divalent cations that reduce polymyxin activity

Calcium and magnesium.

Antibacterial activity of polymyxins is decreased by

Unsaturated fatty acids.

Antibacterial activity of polymyxins is decreased by

Acidic phospholipids.

Antibacterial activity of polymyxins is decreased by

Quaternary ammonium compounds.

Antibacterial activity of polymyxins is decreased by

Anionic detergents.

Most important toxicity of polymyxins

Nephrotoxicity.

Mechanism of polymyxin nephrotoxicity

Reduced tubular perfusion.

Effect of polymyxin nephrotoxicity

Decreased urine output.

Second major toxicity of polymyxins

Neurotoxicity.

Examples of polymyxin neurotoxicity

CNS depression, anorexia, and neuromuscular blockade.

Type of paralysis caused by polymyxins

Curare-like paralysis.

Polymyxin-induced neuromuscular blockade is additive with

Other neuromuscular blocking drugs.

Polymyxin B is a potent releaser of

Histamine.

Rapid IV administration of polymyxins may cause

Respiratory paralysis.

Respiratory paralysis risk increases in

Animals with preexisting renal disease.

Most dangerous systemic adverse effects of polymyxins

Nephrotoxicity and neurotoxicity.

Why systemic polymyxin therapy is generally avoided

High risk of nephrotoxicity and neurotoxicity.

Topical polymyxin administration is generally

Safe.

Oral polymyxin administration is generally

Safe.

Reported adverse effects of topical polymyxins

None significant.

Reported adverse effects of oral polymyxins

None significant.

High-yield association

Polymyxins = Gram-negative bacteria.

High-yield association

Polymyxins = Pseudomonas.

High-yield association

Polymyxins = E. coli diarrhea.

High-yield association

Polymyxins = Salmonella diarrhea.

High-yield association

Polymyxins = Otitis externa.

High-yield association

Polymyxins = Poor oral absorption.

High-yield association

Polymyxins = Poor CSF penetration.

High-yield association

Polymyxins = Renal elimination.

High-yield association

Polymyxins = Nephrotoxicity.

High-yield association

Polymyxins = Neurotoxicity.

High-yield association

Polymyxin B = Histamine release.

High-yield association

Polymyxins = Respiratory paralysis with rapid IV administration.

High-yield association

Polymyxins + Tetracyclines = Synergism.

High-yield association

Polymyxins + Chloramphenicol = Synergism.

High-yield association

Polymyxins + Sulfonamides = Synergism.

High-yield association

Proteus = Resistant.

High-yield association

Serratia = Resistant.

Most important exam toxicity

Nephrotoxicity.

Most important exam interaction

Synergism against Pseudomonas aeruginosa.

Most important exam pharmacokinetic fact

Polymyxins do not enter the CSF.

Most important exam clinical use

E. coli and Salmonella diarrhea.

Most important exam organism

Pseudomonas aeruginosa.