Infusion, continuous

The drug is metabolized rapidly in the liver, kidney, intestinal mucosa, and even red blood cells. Therefore it has a plasma half-life of only 10 min after bolus intravenous application. The major metabolite, uracil arabinoside (ara-U), can be detected in the blood shortly after cytarabine administration. About 80% of the dose is excreted in the urine within 24 h, with less than 10% appearing as cytarabine the remainder is ara-U. After continuous infusion, cytarabine levels in the liquor (cerebro-spinal fluid) approach 40% of that in plasma. Continuous infusion schedules allow maximal efficiency, with uptake peaks of 5-7 pM. It can be administered intrathecally as an alternative to methotrexate. 

Prostacyclin (epoprostanol) is one of the few drugs effective for the treatment of Primary Pulmonary Hypertension (PPH) a rare but frequently fatal illness of young adults. Increased blood pressure in the pulmonary circulation leads to right-heart failure. Continuous infusion of epoprostanol leads to a decrease in blood pressure however, it is unclear whether this is due to direct dilator activity of the IP receptor acting on smooth muscle, or a more indirect mechanism. 

Administration of oxytocin may result in fetal bradycardia, uterine rupture, uterine hypertonicity, nausea, vomiting, cardiac arrhythmias, and anaphylactic reactions. Serious water intoxication (fluid overload, fluid volume excess) may occur, particularly when the drug is administered by continuous infusion and the patient is receiving fluids by mouth. When used as a nasal spray, adverse reactions are rare. 

Kruizinga, W., and Hillen, F. C. (1989b). A comparative study on antitumor effect, cardiotoxicity and nephrotoxicity of doxorubicin administered as bolus, continuous infusion or entrapped in liposomes in the Lou/M Wsl rat, Cancer Chemother. Pharmacol. 24, 341-348. 

Heparin must be given parenterally as it is not absorbed by the gut due to the large size and charge of its constituent molecules. Because of its short half-life (approximately 1 hour) UFH must be given frequently or as a continuous infusion. 

If a stroke patient receives intravenous (IV) thrombolysis, care often continues in the ED until the patient arrives in the ICU. Close monitoring must continue during this time, with special attention to the blood pressure. The blood pressure is most commonly checked via an arm cuff, since the placement of invasive lines (e.g., arterial catheterization) is relatively contraindicated once the patient has received intravenous thrombolysis (unless the situation is emergent and mandates such treatment). The systolic pressure must not exceed 185 mm Hg, and the diastolic pressure limit should be 110 mm Hg. Should the blood pressure exceed these limits, IV antihypertensive agents should be administered. IV pushes of labetolol (10-20 mg over 1-2 minutes) may be effective, but if patients are refractory to these initial measures then a continuous infusion of labetolol (0.5-2.0 mg/minute), nicardipine (5-15 mg/hour), or nitro-prusside (0.25-10 mg/kg/minute) may be necessary to keep the patient s blood pressure within the range. There will be a more detailed discussion of these antihypertensive agents, including their side effect profiles, later in this chapter. 

Hypertonic sahne is actively excluded from an intact BBB and also acts to draw water into the intravascular space by the creation of a sodium gradient. Various concentrations have been evaluated, with continuous sodium chloride infusions ranging from 3% to 9%, and bolus infusions up to 23.4% administered over 20 minutes in a 30 mL solution. When a continuous infusion is used, the serum sodium is typically titrated to the 155-160 range. Sodium levels above this range raise the concern for seizures and other toxic side effects. Hypertonic saline may hold an advantage over mannitol, as it has been found in animal models to decrease edema in both... 

These effects could result from the progression of the disease but as they are a feature of levodopa therapy a change in the central response to levodopa or changes in its peripheral kinetics are more likely. The latter does not occur since the maximum plasma concentration, the time to reach it and the plasma half-life are still similar after 10 years of treatment to those achieved initially, although continuous infusion of dopa can smooth out the swings. 

Non-neuronal transplants such as adrenal chromaffin cells have been tried but do not survive although some L-dopa-producing cell lines (e.g. PC 12) or glomus cells of the carotid body do produce DA in vivo and may provide the equivalent of a continuous infusion of dopa (and DA) directly into the brain. Expression of tyrosine hydroxylase to promote dopa and DA synthesis in striatal cells by direct gene transfer in vivo or in cultures for subsequent transplanting, may also be possible. (See Dunnett and Bjorklund 1999 for a review of these approaches.)... 

Nitta, A, Fukuta, T, Hasegawa, T and Nabeshima, T (1997) Continuous infusion of -amyloid proteins into cerebral ventricle induces learning impairment and neuronal and morphological degeneration. Jpn J. Pharmacol. 73 51-57. 

Acute pancreatitis has been induced in dogs by retrograde intraductal injections of 5% hydrogen peroxide solution and sunflower oil (Keleman and Torok, 1990) and in rats by continuous infusion of xanthine/XO or hydrogen peroxide into the coeliac artery (Tamura et al., 1991a). Xanthine/XO has also been shown to be toxic, as measured by release of LDH, to in vitro rat pancreatic acini (Tamura et al., 1991b). 

Schiffrin, E.J., Trop, M., Agarinakazato, O., Bustos-Fernandez, L.M., Bustos-Fernandez, L. and Carter, E.A. (1991). Continuous infusion of lipopolysaccharide a model of inflammatory bowel disease in the rat. Gastroenterology 100, A614. 

Often, it is required to predict the time course of the plasma concentration from a model with oral administration or with continuous infusion, when only data from a single intravenous injection are available. In this case, the Laplace transform can be very useful, as will be shown from the following illustration. 

Monitor activated partial thromboplastin time (aPTT) 2 h after the start of the continuous infusion... 

Use continuous infusion instead of intermittent bolus feeding... 

Onset of Action (minutes) Duration of Action (hours) Relative Potency Intermittent Bolus Dosing (mg) Continuous Infusion Dosing (bolus/infusion)... 

Continuous infusions of nitroglycerin should be initiated at a dose of 5 to 10 mcg/minute and increased every 5 to 10 minutes until symptomatic or hemodynamic improvement. Effective doses range from 35 to 200 mcg/minute. The most common adverse events reported are headache, dose-related hypotension, and tachycardia. A limitation to nitroglycerin s use is the development of tachyphylaxis, or tolerance to its effects,... 

P-Blockersa Inhibit AV nodal conduction by slowing AV nodal conduction and prolonging AV nodal refractoriness Esmolol 500 mcg/kg IV over 1 minute Propranolol 0.15 mg/kg IV Metoprolol 2.5-5 mg IV x 2-3 doses Esmolol 50-200 mcg/kg/minute continuous infusion Propranolol 80-240 mg/day Metoprolol 50-200 mg/day ... 

Diltiazem Inhibits AV nodal conduction by slowing AV nodal conduction and prolonging AV nodal refractoriness 1.0.25 mg/kg IV load over 2 minutes 2. If necessary, 0.35 mg/kg IV over 2 minutes after first dose Continuous infusion of 5-1 5 mg/hour Oral 120-360 mg/day Inhibits elimination of cyclosporine... 

Treatment Loading Dose Continuous Infusion Rate Drug Interactions... 

Procainamide 12-17 mg/kg IV, no faster than 20 mg/minute 1-4 mg/minute continuous infusion... 

Amiodarone 150 mg IV over 10 minutes 1 mg/minute continuous infusion for 6 hours, 0.5 mg/ minute for 18 hours... 

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