Intravascular metabolism

It can be expected that all plasma lipoprotein classes, defined in one way or another, consist of a variety of subfractions, simply because plasma lipoproteins form a dynamic system. Plasma lipoprotein metabolism starts as soon as the nascent particles are secreted. Subsequent intravascular metabolism includes the actions of lipoprotein lipase, hepatic lipase, lecithin cholesterol acyltransferase (LCAT), and lipid transfer proteins (LTP). In addition, most lipoproteins can bind to lipoprotein receptors. This can be foUowed by uptake and irreversible intracellular degradation of the holo-particle, or by reappearance in plasma of a modified form of the lipoprotein. The modifications may be due to the transfer of cellular lipids to plasma lipoproteins or to the specific transfer of lipoprotein components to the cells. Both mechanisms may include retroendocytosis. 

S. H. Untracht, Intravascular metabolism of an artificial transporter of triacylglycerols. Biochem. Biophys. Acta, 711, 176-192 (1982). 

Poorly treated hyperthermia may lead to metabolic acidosis, rhabdomyolysis, elevated aminotransferases, seizures, renal failure, and disseminated intravascular coagulation (DIC)... 

Hypovolemic shock occurs as a consequence of inadequate intravascular volume to meet the oxygen and metabolic needs of the body. 

In PD, prewarmed dialysate is instilled into the peritoneal cavity where it dwells for a specified length of time (usually one to several hours, depending on the type of PD) to adequately clear metabolic waste products. At the end of the dwell time, the dialysate is drained and replaced with fresh dialysate. The continuous nature of PD provides for a more physiologic removal of waste products from the bloodstream, which mimics endogenous renal function by decreasing the fluctuations seen in serum concentrations of the waste products. Similarly, water is removed at a more constant rate, lessening the fluctuations in intravascular fluid balance and providing for more hemodynamic stability. 

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.)...

Patients predicted to follow a severe course require treatment of any cardiovascular, respiratory, renal, and metabolic complications. Aggressive fluid resuscitation is essential to correct intravascular volume depletion and maintain blood pressure. IV colloids may be required because fluid losses are rich in protein. Drotrecogin alfa may benefit patients with pancreatitis and systemic inflammatory response syndrome. IV potassium, calcium, and magnesium are used to correct deficiency states. Insulin is used to treat hyperglycemia. Patients with necrotizing pancreatitis may require antibiotics and surgical intervention. 

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. 

Metabolic alkalosis is generally treated by correction of abnormalities in total body K+, intravascular volume, or mineralocorticoid levels. However, when the alkalosis is due to excessive use of diuretics in patients with severe heart failure, replacement of intravascular volume may be contraindicated. In these cases, acetazolamide can be useful in correcting the alkalosis as well as producing a small additional diuresis for correction of volume overload. Acetazolamide can also be used to rapidly correct the metabolic alkalosis that may develop in the setting of respiratory acidosis. 

Diuretic-induced metabolic alkalosis is another adverse effect that may further compromise cardiac function. This complication can be treated with replacement of K+ and restoration of intravascular volume with saline however, severe heart failure may preclude the use of saline even in patients who have received excessive diuretic therapy. In these cases, adjunctive use of acetazolamide helps to... 

It is important to note that, even more than in heart failure, overly aggressive use of diuretics in this setting can be disastrous. Vigorous diuretic therapy can cause marked depletion of intravascular volume, hypokalemia, and metabolic alkalosis. Hepatorenal syndrome and hepatic encephalopathy are the unfortunate consequences of excessive diuretic use in the cirrhotic patient. 

Metabolic alkalosis is generally treated by correction of abnormalities in total body K+, intravascular volume, or mineralocorticoid levels. 

Intravascular Intravenous (IV) injection is the most common parenteral route. For drugs that are not absorbed orally, there is often no other choice. With IV administration, the drug avoids the Gl tract and, therefore, first-pass metabolism by the liver. This route permits a rapid effect and a maximal degree of control over the circulating levels of the drug. However, unlike drugs present in the Gl tract, those that are injected cannot be recalled by... 

A 41-year-old woman developed seizures that progressed to status epilepticus, and died from secondary rhabdomyolysis and disseminated intravascular coagulation (128). She had been taking olanzapine 10 mg/ day for 5 months. No other toxic, metabolic, or anatomical abnormalities were identified pre- or postmortem to explain the seizures. However, her medications also included levothyroxine 0.15 mg/day, clonazepam 1.0 mg qds, and propranolol 20 mg tds. 

Plasma volume expanders. If blood is lost during trauma, the loss of volume is more immediately threatening than the loss of red blood cells. Replacement with salt solutions does not work well because small solutes get rapidly filtrated into the interstitial fluid compartment. Only macromolecules are retained in the intravascular space and can prevent filtration of the diluted plasma due to their osmotic activity. Commonly used plasma expanders are metabolically inert polysaccharides such as dextran and hydroxyethyl-starch. 

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