Effect of antibiotics and sedatives on normal neutrophil nicotinamide-adenine dinucleotide phosphate-reduced oxidase activity

• Published in: Archives of surgery (Chicago. 1960) Vol. 121; no. 1; p. 73
• Main Authors: Moon, B C, Girotti, M J, Wren, S F, Dawson, R, Brar, D
• Format: Journal Article
• Language: English
• Published: United States 01.01.1986
• Subjects: Adult; Anti-Bacterial Agents - pharmacology; Cefamandole - analogs & derivatives; Cefamandole - pharmacology; Clindamycin - analogs & derivatives; Clindamycin - pharmacology; Diazepam - pharmacology; Female; Humans; Hypnotics and Sedatives - pharmacology; In Vitro Techniques; Male; Middle Aged; Morphine - pharmacology; N-Formylmethionine Leucyl-Phenylalanine - pharmacology; NADH, NADPH Oxidoreductases - blood; NADPH Oxidases; Neutrophils - drug effects; Penicillin G - pharmacology; Stimulation, Chemical; Tobramycin - pharmacology
• ISSN: 0004-0010
• DOI: 10.1001/archsurg.1986.01400010079010

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.