Effect of antibiotics and sedatives on normal neutrophil nicotinamide-adenine dinucleotide phosphate-reduced oxidase activity.
The effects of antibiotics and other commonly used medications on the human polymorphonuclear neutrophil leukocytes' (PMNs) nicotinamide-adenine dinucleotide phosphate-reduced (NADPH) oxidase activity have been investigated in vitro. Five antibiotics (penicillin G sodium, cefamandole nafate, metronidazole hydrochloride, clindamycin phosphate, and tobramycin sulfate, and a triple combination of penicillin G sodium-metronidazole hydrochloride-tobramycin sulfate) and two sedatives (morphine sulfate and diazepam) were incubated with normal human PMNs at therapeutic, infratherapeutic, and supratherapeutic drug levels. The superoxide dismutase-inhibitable, NADPH-dependent reduction of cytochrome C in the PMNs was studied after stimulation with formyl-methionyl-leucine-phenylalanine. Tobramycin sulfate and the triple combination of penicillin G sodium-metronidazole hydrochloride-tobramycin sulfate significantly reduced the NADPH oxidase activity at all dosages studied. Clindamycin phosphate, morphine sulfate, and diazepam also showed significant reduction at therapeutic and supratherapeutic concentrations. Penicillin G sodium, cefamandole nafate, and metronidazole hydrochloride did not cause a decrease in enzyme activity at any levels tested. We conclude that NADPH oxidase activity can be adversely affected by the circulating levels of common antibiotics and sedatives.
D000328:Adult; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002435:Cefamandole / Q000031:analogs & derivatives / Q000494:pharmacology; D002981:Clindamycin / Q000031:analogs & derivatives / Q000494:pharmacology; D003975:Diazepam / Q000494:pharmacology; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000494:pharmacology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009247:NADH, NADPH Oxidoreductases / Q000097:blood*; D019255:NADPH Oxidases; D009504:Neutrophils / Q000187:drug effects*; D010400:Penicillin G / Q000494:pharmacology; D013268:Stimulation, Chemical; D014031:Tobramycin / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D006993:Hypnotics and Sedatives; D002981:Clindamycin; D009240:N-Formylmethionine Leucyl-Phenylalanine; D002435:Cefamandole; D009020:Morphine; C012810:cefamandole nafate; D009247:NADH, NADPH Oxidoreductases; D019255:NADPH Oxidases; C007084:clindamycin phosphate; D003975:Diazepam; D010400:Penicillin G; D014031:Tobramycin