Excretion mechanisms

No evidence of exposure-related DNA adduct formation in femur bone marrow, Zymbal gland, liver, or spleen was seen in rats treated orally with 75 mg/kg/day phenol for 4 days (Reddy et al. 1990). In this study, concurrent in vitro exposures of these tissues did produce adducts, suggesting that efficient detoxification and excretion mechanisms may be operating in vivo. 

Sugiyama, Y., Kato, Y., and Chu, X. (1998) Multiplicity of bdiary excretion mechanisms for the camptothecin derivative irinotecan (CPT-11), its metabolite SN-38, and its glucuronide role of canalicular multispecific organic anion transporter and P-glycoprotein. Cancer Chemother. Pharmacol. 42(suppl), S44-S49. 

Iron is an essential element, for humans and for many forms of life, but even a modest excess can be toxic as the human body does not have an effective iron excretion mechanism. It is therefore necessary to maintain an appropriate level of iron in the body, to supply iron in absorbable form if it is deficient (anemia) and to remove iron if present in excess. Inorganic coordination chemistry plays an important role in dealing with these complementary conditions of deficiency and of excess. The latter condition is much more common than often supposed, for there are a number of conditions, such as hemochromatosis and thallasemia, where the build-up of iron in essential organs is eventually lethal. Mild iron poisoning is not infrequent in children, while even iron fortification of foodstuffs can have adverse effects. Mild iron poisoning can be treated with bicarbonate or phosphate, which presumably complex and precipitate the iron. ... 

Lithium intoxication can be precipitated by the use of diuretics, particularly thiazides and metola-zone, and ACE inhibitors. NSAIDs can also precipitate lithium toxicity, mainly due to NSAID inhibition of prostaglandin-dependent renal excretion mechanisms. NSAIDs also impair renal function and cause sodium and water retention, effects which can predispose to interactions. Many case reports describe the antagonistic effects of NSAIDs on diuretics and antihypertensive drugs. The combination of triamterene and indomethacin appears particularly hazardous as it may result in acute renal failure. NSAIDs may also interfere with the beneficial effects of diuretics and ACE inhibitors in heart failure. It is not unusual to see patients whose heart failure has deteriorated in spite of increased doses of frusemide who are also concurrently taking an NSAID. 

These drugs are basically anion exchange resins that remain in the gut, bind intestinal bile acids, and greatly increase their fecal excretion (mechanism I in Fig. 23.2). 

Two main effects occur here. First, change in the pH of urine—weak bases, such as pethidine, are more easily excreted in an acid urine while alkalinisation promotes excretion of weak acids, such as salicylates and phenobarbital. Second, drugs that compete for an active excretion mechanism will reduce each other s elimination—probenecid was used in the early days of penicillin to conserve the drug, while less desirable interactions also occur, e.g. chlorpropamide and phenylbutazone interact to give increased levels of chlorpropamide and a danger of hypoglycaemia. 

Levine WG. Excretion mechanisms. In Caldwell J, Jakoby WB, eds. Biological Basis of Detoxication. New York Academic Press, 1983. 

It should be noted, however, that as the toxicant is being absorbed and distributed throughout the body, it is being simultaneously eliminated by various metabolism and/or excretion mechanisms, as will be discussed in more detail in the following chapters. However, one should mention here that an important pharmacokinetic parameter known as clearance Cl) can be used to quantitatively assess elimination of a toxicant. Clearance is defined as the rate of toxicant excreted relative to its plasma concentration, Cp ... 

Wilson s disease is a copper storage disorder that is apparently due to an inherited lesion in the copper excretion mechanism. One in 200-400 persons is a carrier of the disease. Diagnosis may be made by measuring serum ceruloplasmin levels. Whereas normal serum ceruloplasmin is 200-400 mg/L, in Wilson s disease patients it is well below 200 mg/L. Liver copper in these patients (determined by biopsy) is more than 250 /xg/g, whereas normal individuals show a value of only 20-45 /xg/g. Liver function deterioration is the most prominent symptom of Wilson s disease. Treatment includes chelation therapy with penicillamine. 

The possibilities for synergism, antagonism, and potentiation among chemicals, the allergic type responses, and the impaired detoxification and excretion mechanisms in substantial groups of people all call for less... 

Nearly every drug, if administered in excessive amounts, may produce toxic effects.Toxic levels of drugs can result even when daily doses are in the normal therapeutic ranges if administration is prolonged or when other drugs potentiate the effects or when drug detoxification or excretion mechanisms operate more slowly than expected. The effect of excessive drug intake has been observed... 

Distribution, Metabolism, and Excretion Mechanisms of Opiate Action Discovery of Endorphins What Do Endorphins Do ... 

We begin this chapter with a historical overview of marijuana and its use through the centuries. This is followed by a section on the epidemiology of current marijuana use. Next we provide information on absorption, distribution, metabolism, and excretion mechanisms of action and tolerance and dependence. Follow ing this is an overview of the medical and p-sychotherapeutic uses of marijuana. The chapter s final sections concern the physical, psychological, and social/environmental effects of marijuana. 

Urine is the most important excretion mechanism in humans. Urine concentration of cadmium increases with age and following kidney damage. Cadmium found on examination of hair is generally due to external contamination rather than internal absorption and distribution to the hair. 

Renal excretion mechanisms appear to mature within the first 2 weeks after birth in foals, calves, lambs, kids and piglets, while their maturation in puppies may take 4-6 weeks. In a study of the pharmacokinetics of amikacin in critically ill full-term foals ranging in age from 2 to 12 days, the systemic clearance of the aminoglycoside was lower (indicating impaired renal function) and the half-life was considerably prolonged in uraemic compared with non-uraemic foals (Adland-Davenport et al., 1990). 

Ando, T., Kusuhara, H., Merino, G., Alvarez, A.I., Schinkel, A.H. and Sugiyama, Y. (2007) Involvement of breast cancer resistance protein (ABCG2) in the biliary excretion mechanism of fluoroquinolones. Drug Metabolism and Disposition The Biological Fate of Chemicals, 35, 1873-1879. 

Question Drug H has a clearance rate of 400 mL/min in people with normal renal function. What can be determined about the renal excretion mechanism (note that GFR is 125 mL/min) ... 

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