Plasma effects, localized

Potassium intoxication Do not infuse rapidly. High plasma concentrations of potassium may cause death through cardiac depression, arrhythmias, or arrest. Monitor potassium replacement therapy whenever possible by continuous or serial EGG. In addition to EGG effects, local pain, and phlebitis may result when a more than 40 mEg/L concentration is infused. 

Eecause ascorbic acid and other antioxidants in plasma effectively prevent lipid peroxidation and, hence, oxidative modification of LDL, it is likely that LDL oxidation in vivo occurs in microenvironments of the arterial wall rather than the circulation (Steinberg et al., 1989). Water-soluble antioxidants such as ascorbic acid may be excluded from these lipid-rich microenvironments in the artery wall (Eelcher et al, 1993), or these antioxidants may be rapidly depleted due to high levels of local oxidative stress (e.g., in the microenvironment of activated macrophages). Thus, in the above cited study of ODS rats (Kimura et al, 1992), it is unlikely that LDL oxidation occurred in the circulation. Rather, vitamin C deficiency may have facilitated LDL oxidation in the arterial wall, followed by release of some modified LDL into the circulation. Although the antioxidant composition of the extracellular fluid in the arterial wall has not been characterized, we have found that a model of human interstitial fluid (Vessby et al, 1987) is characterized by an ascorbic acid concentration that is similar to plasma (Dabbagh and Frei, 1994). 

Electrotransport technology offers a number of benefits for therapeutic appHcations, including systemic or local adininistration of a wide variety of therapeutic agents with the potential adininistration of peptides and proteins long-term noninvasive administration, improving convenience and compliance controlled release, providing a desired deflvery profile over an extended period with rapid onset of efficacious plasma dmg levels and in some cases reduced side effects and a transport rate relatively independent of skin type or site. Additional benefits include easy inception and discontinuation of treatment, patterned and feedback-controlled deflvery, and avoidance of first-pass hepatic metaboHsm. 

Neurological effects related to cholinesterase depression occurred in seven children acutely exposed to methyl parathion by inhalation as well as orally and dermally (Dean et al. 1984). The children were admitted to a local hospital with signs and symptoms of lethargy, increased salivation, increased respiratory secretions, and miosis. Two of the children were in respiratory arrest. Two children died within several days of each other. All of the children had depressed plasma and erythrocyte cholinesterase levels (Table 3-2). These effects are similar to those occurring in methyl parathion intoxication by other routes (see Sections 3.2.2.4 and 3.2.3.4). Three adults exposed in the same incident had normal plasma (apart from one female) and red blood cell cholinesterase, and urinary levels of 4-nitrophenol (0.46-12.7 ppm) as high as some of the ill children. 

J. Guern, J. P. Renaudin, S. C. Brown, The compartmentation of secondary metabolites in plant cell cultures. Cell Culture and Somatic Cell Genetics of Plants. Vol. 4 (F, Constabel and 1. K. Vasil, eds.). Academic Press, San Diego, 1987, p. 43. A. L. Samuels, M. Fernando, and A. D. M. Glass, Immunofluorescent localization of plasma membrane H -ATPase in barley roots and effects of K nutrition. Plant Physiol. 99 1509 (1992). 

An initial burst effect was observed in all in vivo studies. There are several possible factors which may cause a burst effect physically absorbed free drug, surface effects, and local tissue inflammation during the initial period of injection. It has been shown that inflammation decreases local tissue pH (15,16) and causes release of hydrolytic enzymes which would increase the hydrolysis of labile bonds, thereby increasing the release of the drug and, subsequently, increasing plasma levels of drug. 

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