Metabolic inhibitors effect

Kehrer, J. P Witschi, H. Effects of drug metabolism inhibitors on butylated hydroxyto-luene-induced pulmonary toxicity in mice. Toxicol. Appl. Pharmacol 1980,53,333-342. 

Rees, J.F. and F. Baguet. 1989. Metabolic control of luminescence in the luminous organs of the teleost Porichthys effects of the metabolic inhibitors iodoacetic acid and potassium cyanide. Jour. Exper. Biol. 143 347-357. 

Pretreatment with the Type I substrate, ethylmorphine, resulted in 100% mortality in both rats and mice, and aminopyrine pretreatment resulted in 100% and 64% mortality in rats and mice, respectively, exposed to disulfoton (Pawar and Fawade 1978). Nickel chloride, cobalt chloride, or cycloheximide decreased the levels of cytochrome bs, cytochrome c reductase, and total heme in rats (Fawade and Pawar 1983). These electron transport components were further decreased in rats pretreated with these inhibitors and given a single dose of disulfoton. Data from this study suggests an additive effect, since disulfoton also decreases the activities of these components. Evidence of an additive effect between disulfoton and these metabolic inhibitors was suggested by the decrease in ethylmorphine N-demethylase and acetanilide hydroxylase activities when rats were given an inhibitor followed by disulfoton. In another experiment, these inhibitors decreased the activity of delta-aminolevulinic acid synthetase, but this decrease was reversed when disulfoton was administered. 

Sakagami M, Byron PR, Rypacek F (2002) Biochemical evidence for transcy-totic absorption of polyaspartamide from the rat lung effects of temperature and metabolic inhibitors. J Pharm Sci 91 1958-1968. 

There may also be effects via the concentrations of competing cations at the root surface. In studies of short-term uptake of Zn by rice from nutrient solutions containing realistic Zn " " concentrations, Giordano and Mortvedt (1974) found uptake was inhibited by various metabolic inhibitors and by Fe +, Mn +, Ca and Mg + as Cl salts at typical concentrations in flooded soil solutions. Translo-... 

DC041 Ton, P. C., and S. K. Sarkar. Biosynthesis of isocoumarins in carrot roots tissues. Induction by substances other that ethylene and effects of metabolic inhibitors. Rev Can Biol 1975 34 23. 

Cardiovascular side effects. Ziprasidone produced a mean QTc prolongation of 21 ms at maximal blood levels achieved with typical therapeutic doses. However, in all clinical trials, the rate of QTc intervals greater than 500 ms (considered a threshold for arrhythmia risk) did not differ from the rate associated with placebo (<0.1%). The QTc effect of ziprasidone is larger than that of other atypical antipsychotics but smaller than that of thioridazine. Blood levels of ziprasidone increased about 40% when ketoconazole (a metabolic inhibitor) was coadministered, and no change in QTc duration was detected. 

This type of effect can occur in all tissues and is caused by a metabolic inhibitor such as azide or cyanide, which inhibits the electron transport chain. Inhibition of one or more of the enzymes of the tricarboxylic acid cycle such as that caused by fluoroacetate (Fig. 6.7) also results in inhibition of cellular respiration (for more details of cyanide and fluoroacetate see chap. 7). 

B. Effects of Known Lipid Metabolism Inhibitors on the Assays... 

Karaki H, Ikeda M, Urakawa N. 1967. Effects of external calcium and some metabolic inhibitors on barium-induced tension changes in guinea pig taenia coli. Jpn J Pharmacol 17 603-612. 

Funk, C. and Brodelius, P.E. (1 990b) Phenylpropanoid metabolism in suspension cultures of Vanilla planifolia Andr. II. Effects of precursor feeding and metabolic inhibitors. Plant Physiology 94, 95-101. 

Conventional methods for establishing the existence of active transport are to analyze the effects of metabolic inhibitors, to correlate the rate of metabolism with the extent of ion flow or the concentration ratio between the inside concentration and the outside concentration of the cells, and to measure the current needed in a short-circuited system having identical compositions solution on each side. Measurements indicate that the flow contributing to the short-circuited current, and ary net flow detected are due to active transport, since the electrochemical gradients of all ions are zero (A // = 0, c0 = c,). 

By using radioisotopes, the influx of vanadate into the blood cells of A. nigra has been studied85. The influx of phosphate, sulfate and dichromate, and the inhibitory effect of these oxoanions on vanadate influx have also been determined. The rate of vanadate influx was measured in the presence of metabolic inhibitors and inhibitors of anion transport. In this study, EPR spectroscopy was used to follow changes in the concentration of reduced vanadium within tunicate blood cells exposed to vanadate. 

Isoniazid inhibits monoamine oxidase, and hence reduces tyramine metabolism this effect is enhanced by co-administration of other monoamine oxidase inhibitors... 

After the addition of stiripentol (50 mg/kg) in 20 children treated with clobazam, mean serum clobazam concentrations increased about twofold and norclobazam concentrations increased about threefold a mean 25% reduction in clobazam dose was required because of adverse effects (15). Serum concentrations of concomitantly administered valproic acid rose by about 20%. These findings are in agreement with evidence that stiripentol is a potent metabolic inhibitor. 

CICLOSPORIN AZOLES - ITRACONAZOLE, KETOCONAZOLE, VORICONAZOLE t plasma concentrations of ciclosporin, with risk of nephrotoxicity, myelosuppression, neurotoxicity, excessive immunosuppression, with risk of infection and post-transplant lymphoproliferative disease Inhibition of CYP3A4-mediated metabolism of ciclosporin these inhibitors vary in potency. Ketoconazole and itraconazole are classified as potent inhibitors. Effect not clinically relevant with fluconazole Avoid co-administration with itraconazole or ketoconazole. Consider alternative azole but need to monitor plasma ciclosporin levels to prevent toxicity... 

Cass WA, Zahniser NR, Flach KA, Gerhardt GA. Clearance of exogenous dopamine in rat dorsal striatum and nucleus accumbens role of metabolism and effects of locally applied uptake inhibitors. J. Neurochem. 1993 61 2269-2278. 

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