Intravenous systems

Systemic targeting of pDNA and siRNA polyplexes has been demonstrated in several animal models. In continuation of the work with localized antiproliferative and immunostimulatory poly(I C) RNA, intravenous systemic delivery of EGER-targeted PEG-modified polyplexes were successfully used for human carcinoma treatment in mice [225]. The therapeutic effect was most pronounced when intravenous delivery of poly(I C) polyplexes was followed by intraperitoneal injection of peripheral blood mononuclear cells [226]. This induced the complete cure of SCID mice with pre-established disseminated EGFR-overexpressing tumors, without adverse toxic effects. Due to the chemokines produced by the internalized poly (I C) in the tumor cells, the immune cells home to the tumors of the treated animal and contribute to the tumor destruction. 

The renin-angiotensin system plays a major role in the regulation of arterial blood pressure. Modest increases in plasma concentrations of Angll. When a single moderate dose of Angll is injected intravenously, systemic blood pressure begins to rise within seconds, peaks rapidly, and returns to... 

The indwelling central venous catheter should be maintained as an intravenous life-line. That the catheter should be used exclusively for delivery of the intravenous nutrient solution is inherent in this philosophy. The temptation to withdraw blood via the catheter, to use the catheter for frequent central venous pressure monitoring, to inject bolus medication via the catheter, or to use the catheter for blood or blood constituent administration must be repressed. Three-way stopcocks within the delivery system must be condemned, because maintenance of the sterility of any intravenous system containing a three-way stopcock is virtually impossible. 

Table 26.1. Colorectal liver metastases treatment. Course of isolated colorectal liver metastases (1979-2002, Department of Surgery 1, Ulm, Germany). FA, folinic acid HAl, hepatic artery infusion La., intra-arterial i.v. intravenous (systemic) MFFM, mitoxantrone + 5-FU + FA + mitomycin C n.d., no data 5-FUDR, 5-fluorodeoxyuridine 5-FU, 5-fluorouracil...

Septicaemia from prolonged intravenous infusions is a well-known complication and it has therefore been generally accepted that infusion sets should not be used longer than 24 hours (maximum 48 hours). Intravenous systems used for over 48 hours have been shown to increase the risk of contamination by 15% as compared with systems in use for less than 48 hours (3%) (12 ). Four cases of septicaemia in children receiving Lv. infusion (5% dextrose-saline) have been observed, all caused by Pseudomonas cepacia contamination (13 ). The isolated strains were sensitive to sulfonamides, co-trimoxazole and chloramphenicol,- but resistant to gentamicin, polymyxin B and other antibiotics. One patient died after a long and comphcated post-operative period. The other 3 recovered after chloramphenicol therapy within 2 weeks. 

Pharmaceutical Industry. In the pharmaceutical industry, sterility of deionized water systems is maintained by using an ozone residual. The ozone residual concentration is maintained at >0.3 ppm ppm in the water recirculation loop. Prior to product compounding, the ozone residual is removed by contact with uvirradiaton for <1 s. Ozone also is used to oxidize pyrogens from distilled water destined for intravenous solutions. 

Biomedical Applications. TRIS AMINO is used for a number of purposes in its pure form, it is an acidimetric standard the USP grade can be utilized intraveneously for therapeutic control of blood acidosis TRIS AMINO also is useful in genetic engineering as a buffering agent for enzyme systems, industrial protein purification, and electrophoresis. AMP has found use as a reagent in enzyme-linked immunoassays. The primary appHcation is for alkaline phosphatase assays. 

Reproductive System. The primary PGs are intimately involved in reproductive physiology (67). PGE2 and PGP2Q, are potent contractors of the pregnant utems and intravenous infusion of either of these compounds to pregnant humans produces a dose-dependent increase in frequency and force of uterine contraction. PGI2 and TXA2 have mild relaxant and stimulatory effects, respectively, on uterine tissue. The primary PGs also play a role in parturition, ovulation, luteolysis, and lactation and have been impHcated in male infertility. 

Thorotrast (colloidal Th02) was once used as a radiopaque agent in medicine (see Radiopaques). Its injection in a dose of 2.0—15.0 g caused rises in body temperature, nausea, and injury to tissues at the injection site, followed by anemia, leukopenia, and impairment of the reticuloendothehal system. After intravenous adrninistration, thorotrast particles are taken up by reticuloendothehal cells of the fiver and spleen. Thorotrast is virtually not eliminated from the body (91). Between 1947 and 1961, 33 cases of cancer of the fiver, larynx, and bronchi and sarcoma of the kidneys, developing from 6 to 24 years after thorotrast administering, have been described in the literature (92). 

In order to induce a toxic effect, local or systemic, the causative material must first come into contact with an exposed body surface these are the routes of exposure. In normal circumstances, and depending on the nature of the material, the practical routes of exposure are by swallowing, inhalation, and skin and eye contact. In addition, and for therapeutic purposes, it may be necessary to consider intramuscular, intravenous, and subcutaneous injections as routes of adininistration. 

Some polymyxins are sold for second-line systemic therapy. Polymyxin B sulfate and colistimethate sodium can be used for intravenous, intramuscular, or intrathecal administration, especially for Pseudomonas aerupinosa mP QXiosis, but also for most other gram-negative organisms, such as those resistant to first-line antibiotics. Nephrotoxicity and various neurotoxicities are common in parenteral, but not in topical, use. Resistance to polymyxins develops slowly, involves mutation and, at least in some bacteria, adaptation, a poorly understood type of resistance that is rapidly lost on transfer to a medium free of polymyxin. Resistance can involve changes in the proteins, the lipopolysaccharides, and lipids of the outer membrane of the cell (52). Polymyxin and colistin show complete cross-resistance. 

Oral treatment offers the advantage of bringing all the lesions at all sites under control, in addition to the absence of unpleasant cosmetic effects. In certain cases, it may be preferable to use oral treatment for C. albicans vaginitis and for extensive and persistent pityriasis versicolor, a skin disorder caused by Pityrosporum orbiculare. In the case of onychomycosis, a combination treatment, topical plus systemic, is required. It is preferable to use oral treatment for deep and systemic mycoses, though intravenous or intrathecal treatment is sometimes required. 

Amphotericin B. Amphotericin B (3), an important polyene antibiotic, is administered almost exclusively via the intravenous route and is therefore discussed in more detail under the systemic antimycotics. The vaginal tablets contain 50 mg amphotericin B, and 100 mg tetracycline base per tablet (see also Antibiotics, tetracyclines). The tablets for oral use contain 50 mg amphotericin B, 250 mg tetracycline base, and 125 mg sodium hexametaphosphate. A combination ointment contains 1 mg fludrocortisone acetate, 2.5 mg neomycin, 0.25 mg gramicidin, and 1 g plastibase in addition to 30 mg amphotericin B (see also Antibiotics, peptides). 

Miconazole. Miconazole (Fig. 2, 7a) is also available as a sterile solution for intravenous infusion. Miconazole has a therapeutic effect on systemic mycoses due to C albicans A.spergillusfumigatus Cyptococcus neoformans Blastomyces dermatitidis Histoplasma capsulatum Coccidioides immitis Paracoccidioides brasiliensis and Petriellidum boydii. 

Future Antimycotics for Systemic Treatment. Two new antimycotics for systemic use have now reached the stage of clinical development. The first is a triazole and fluoride analogue of itraconazole. This compound (saperconazole) is extremely active 2i 2cm.%. Jisperpillus spp. and slightly more soluble. Consequentiy, intravenous adruinistration might be possible (34). The second molecule is terbinafine [91161 -71 -6] an aHylamine, C21H25N, that appears to be particularly active against dermatophytes, just like topical naftifine (35). 

For late-stage disease, in which the central nervous system is impHcated, the compound of choice until recently was melarsoprol (94, Mel B, Arsobal [494-79-1]) for T. b. gambiense or T. b. rhodesiense. The dmg, adrninistered intravenously, is a solution containing a combination of BAT,... 

FIGURE 5.40 Schematic representation of the concentration of a chemical in the plasma as a function of time after an intravenous injection if the body acts as a one-compartment system and elimination of the chemical obeys first-order kinetics with a rate constant... 

According to Biberfeld, palmatine, calumbamine and jatrorrhizine all paralyse the central nervous system in frogs palmatine also produces this effect in mammals and differs from the other two in stopping respiration, probably by paralysis of the respiratory centre. All three alkaloids lower the blood pressure on intravenous injection, palmatine being the most active. 

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