Intravascular administration

Once diagnosed, patients with AlA should avoid aspirin and any other NSAIDs strongly inhibiting COX-1 their education is of utmost importance. They should receive a list of contraindicated and well-tolerated analgesics (table 2). Even topical administration (intravascular or by iontophoresis) of a NSAID may cause an asthma attack and should be avoided. 

We reconsider the data used previously in Section 39.1.2 in the discussion of the two-compartment system for extravascular administration (e.g. oral, subcutaneous, intravascular). The data are truncated at 120 minutes in order to obtain a realistic case. It is recalled that these data have been synthesized from a theoretical model and that random noise with a standard deviation of about 0.4 pg T has been superimposed. 

T. Teorell, Kinetics of distribution of substances administered to the body. 1. The extravascular modes of administration. Arch. Int. Pharmacodyn., 57 (1937) 205-225. II. The intravascular modes of administration. Arch. Int. Pharmacodyn., 57 (1937) 226-240. 

Understanding the effects of colloid administration on circulating blood volume necessitates a review of those physiologic forces that determine fluid movement between capillaries and the interstitial space throughout the circulation (Fig. 10—5).4 Relative hydrostatic pressure between the capillary lumen and the interstitial space is one of the major determinants of net fluid flow into or out of the circulation. The other major determinant is the relative colloid osmotic pressure between the two spaces. Administration of exogenous colloids results in an increase in the intravascular colloid osmotic pressure. In the case of isosomotic colloids (5% albumin, 6% hetastarch, and dextran products), initial expansion of the intravascular space is essentially that of the volume of colloid administered. In the case of hyperoncotic solutions such as 25% albumin, fluid is pulled from the interstitial space into the vasculature... 

A 48-year-old woman was admitted to the intensive care unit with sepsis and hemodynamic instability. Three days earlier, she had undergone an abdominal surgery. After treatment with intravenous antibiotics and fluid administration, the patient was described as stable. Several hours later, the patient s nurse identified extravasation from the intravascular lines and abdominal drains. 

In patients with peritonitis, hypovolemia is often accompanied by acidosis, so large volumes of a solution such as lac-tated Ringers may be required initially to restore intravascular volume. Maintenance fluids should be instituted (after intravascular volume is restored) with 0.9% sodium chloride and potassium chloride (20 mEq/L) or 5% dextrose and 0.45% sodium chloride with potassium chloride (20 mEq/L). The administration rate should be based on estimated daily fluid loss through urine and nasogastric suction, including 0.5 to 1.0 L for insensible fluid loss. Potassium would not be included routinely if the patient is hyperkalemic or has renal insufficiency. Aggressive fluid therapy often must be continued in the postoperative period because fluid will continue to sequester in the peritoneal cavity, bowel wall, and lumen. 

Thrombomodulin. In patients with SIRS and DIC due to sepsis the serum soluble TM level was higher than in nonseptic and non-DIC patients (A9, B32, G3, II, K7). In experimental ARDS in rats induced by LPS, administration of soluble recombinant TM inhibited the occurrence of intravascular coagulation and prevented the increase in pulmonary vascular permeability (Ul). 

Figure 14.1 Structures of chlorpyrifos and some of its metabolites. (Modified from Barron, M.G., S.M. Plakas, and PC. Wilga. 1991. Chlorpyrifos pharmacokinetics and metabolism following intravascular and dietary administration in channel catfish. Toxicol. Appl. Pharmacol. 108 474-482.)...

Bolus diuretic administration decreases preload by functional venodilation within 5 to 15 minutes and later (>20 min) via sodium and water excretion, thereby improving pulmonary congestion. However, acute reductions in venous return may severely compromise effective preload in patients with significant diastolic dysfunction or intravascular depletion. 

The theoretical advantage of colloids is their prolonged intravascular retention time compared to crystalloid solutions. Isotonic crystalloid solutions have substantial interstitial distribution within minutes of IV administration, but colloids remain in the intravascular space for hours or days, depending on factors such as capillary permeability. However, even with intact capillary permeability, the colloid molecules eventually leak through capillary membranes. 

Donker, A. J. et al., Effects of prolonged administration of D-penicillamine or captopril in various strains of rats. Brown Norway rats treated with D-penicillamine develop autoantibodies, circulating immune complexes, and disseminated intravascular coagulation. Clin. Immunol. Immunopathol., 30, 142, 1984... 

Hypotension/Votume- or salt-depleted patients In patients who are intravascularly volume-depleted (eg, those treated with diuretics), symptomatic hypotension may occur. Correct these conditions prior to administration. 

Pulmonary disease The pulmonary extraction of alprostadil following intravascular administration was reduced by 15% in patients with acute respiratory distress syndrome (ARDS). 

Parenteral administration Inadvertent intravascular administration, including direct... 

Parr RM, Lucas HF Jr., Griem ML. 1968. Metabolism of Th decay series radionuclides in man and other animals following intravascular administration of Thorotrast. ANL-7615. U.S. AEC Argonne Natl Lab, 97-115. 

Amide-type agents include articaine, lidocaine, bupivacaine, prilocaine, mepivacain and ropiva-caine. These are metabolized in the liver by microsomal enzymes with amidase activity. The amide group is preferred for parenteral and local use. If by accident rapidly administered intravascularly these agents, especially bupivacaine but also lidocaine, can produce serious and potentially lethal adverse effects including convulsions and cardiac arrest. They can more easily accumulate after multiple administrations. Intravenous lidocaine is sometimes used for regional anesthesia, for infiltration procedures, for the induction of nerve blockade and for epidural anesthesia. However, it is also used as an antiarrhythmic. Bupivacaine is a long-acting local anesthetic used for peripheral nerve blocks and epidural anesthesia. 

The xanthines are readily absorbed by the oral and rectal routes. Although these agents can be administered by injection (aminophylline is a soluble salt of theophylline), intravascular administration is indicated only in status asthmaticus and apnea in premature infants. Intramuscular injection generally produces considerable pain at the injection site. 

The challenges encountered when developing a PFC-based oxygen carrier are very different from those of the hemoglobin-based products. They concern both the PFC itself and its formulation into a stable, biocompatible emulsion, allowing intravascular administration. 

The MAOIs cause significant hypotension, which is often the dose-limiting side effect of these drugs. Expansion of intravascular volume through administration of salt tablets or fludrocortisone may be an effective treatment. 

There are many natural and biological macromolecules that possess anticancer activity. Cytokines, topoisomerase inhibitors, monoclonal antibodies, thymic hormones, cell growth inhibitors, and enzymes have been used [68], They have been recently reviewed [59,69] and their detailed description is beyond the scope of this article. The main problems connected with the administration of such natural macromolecules is their short intravascular half-life, immunogenicity, and sometimes poor solubility. Their modification with synthetic macromolecules can dramatically increase their therapeutic potential as described below. 

All local anesthetics have the ability to produce sleepiness, light-headedness, visual and auditory disturbances, and restlessness when high plasma concentrations are produced after rapid absorption or inadvertent intravascular administration. An early symptom of local anesthetic toxicity is circumoral and tongue numbness and a metallic taste. At higher concentrations, nystagmus and muscular twitching occur, followed by tonic-clonic convulsions. Local anesthetics... 

Colchicine often causes diarrhea and may occasionally cause nausea, vomiting, and abdominal pain. Hepatic necrosis, acute renal failure, disseminated intravascular coagulation, and seizures have also been observed. Colchicine may rarely cause hair loss and bone marrow depression as well as peripheral neuritis, myopathy, and in some cases death. The more severe adverse events have been associated with the intravenous administration of colchicine. 

This section will review how physiological factors at the site of injection impact the design of dosage forms and affect choice of excipients. First, pharmacokinetic factors affecting rates of delivery of drug to the blood will be considered. Then, biocompatibility or safety issues will be addressed. This analysis focuses on the intravascular (IV), IM, and SC routes of administration. 

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