Phosphate adverse effects

The modes of action for niclosamide are interference with respiration and blockade of glucose uptake. It uncouples oxidative phosphorylation in both mammalian and taenioid mitochondria (22,23), inhibiting the anaerobic incorporation of inorganic phosphate into adenosine triphosphate (ATP). Tapeworms are very sensitive to niclosamide because they depend on the anaerobic metaboHsm of carbohydrates as their major source of energy. Niclosamide has selective toxicity for the parasites as compared with the host because Httle niclosamide is absorbed from the gastrointestinal tract. Adverse effects are uncommon, except for occasional gastrointestinal upset. 

Bd Wt = body weight Cardio = cardiovascular d = day(s) Endocr = endocrine exp. = exposure(s) F = female Gastro = gastrointestinal Hemato = hematological LOAEL = lowest-observed-adverse-effect level M = male Musc/skel = musculoskeletal NOAEL = no-observed-adverse-effect level RBC = red blood cell Resp = respiratory TAP1 = triaryl phosphate hydraulic fluid (TAP1 is similar, if not identical, to Cellulube 220) TPP = triphenyl phosphate wk = week(s) x = times. 

The adverse effect of nonionic adducts of low cloud point can be avoided by the use of hybrid agents of the ethoxylated anionic type, variously and confusingly referred to as modified nonionic , modified anionic or weakly anionic types. Thus Mortimer [113] has proposed the use of products of the ethoxylated phosphate type (12.27). In this structure, R, as well as the degree of ethoxylation (n) may be varied to optimise the overall HLB value. The numerous ether groups are said to enhance the dye-solubilising and levelling capacity, whilst the polyphosphate grouping exerts several useful effects [113]. These compounds ... 

The answer is d. (Katzung, pp 1064-1066J Although A1 hydroxide is generally considered to be the antacid that inhibits phosphate absorption, Ca carbonate is equally capable of this effect. This adverse effect may be hazardous in the presence of renal impairment. 

Adverse effects of calcium-containing phosphate binders, as well as sevel-amer and lanthanum, include constipation, diarrhea, nausea, vomiting, and abdominal pain. The risk of hypercalcemia is also a concern. To avoid potential drug interactions, phosphate binders should be administered 1 hour before or 3 hours after other oral medications. 

High levels of dietary zinc were associated with marked decreases in bone calcium deposition and in the apparent retention of calcium in male weanling albino rats. Marked increases in fecal calcium levels were also observed in the zinc-fed rats. Excessive dietary zinc was associated with a shifting of phosphorus excretion from the urine to the feces. This resulted in an increase in fecal phosphorus and provided an environmental condition which would increase the possibility of the formation of insoluble calcium phosphate salts and a subsequent decrease in calcium bioavailability. The adverse effect of high dietary zinc on calcium status in young rats could be alleviated and/or reversed with calcium supplements. 

The data presented in this paper indicate that excess levels (0.75%) of dietary zinc result in decreases in the bioavailability of calcium and phosphorus in rats and interfere with normal bone mineralization. High dietary levels of calcium or zinc appeared to cause a shift in the excretion of phosphorus from the urine to the feces, while the presence of extra phosphorus tended to keep the pathway of phosphorus excretion via the urine. The presence of large amounts of phosphorus in the Intestinal tract due to high intakes of zinc would increase the possibility of the formation of insoluble phosphate salts with various cations, including calcium, which may be present. A shift in phosphorus excretion from the feces to the urine, however, could result in an environmental condition within the system which would tend to increase the bioavailability of cations to the animal. The adverse effect of zinc toxicity on calcium and phosphorus status of young rats could be alleviated with calcium and/or phosphorus supplements. 

Many of the adverse effects of lithium can be ascribed to the action of lithium on adenylate cyclase, the key enz)nne that links many hormones and neurotransmitters with their intracellular actions. Thus antidiuretic hormone and thyroid-stimulating-hormone-sensitive adenylate cyclases are inhibited by therapeutic concentrations of the drug, which frequently leads to enhanced diuresis, h)rpoth)n oidism and even goitre. Aldosterone synthesis is increased following chronic lithium treatment and is probably a secondary consequence of the enhanced diuresis caused by the inhibition of antidiuretic-hormone-sensitive adenylate cyclase in the kidney. There is also evidence that chronic lithium treatment causes an increase in serum parathyroid hormone levels and, with this, a rise in calcium and magnesium concentrations. A decrease in plasma phosphate and in bone mineralization can also be attributed to the effects of the drug on parathyroid activity. Whether these changes are of any clinical consequence is unclear. 

Occasionally, the phosphate slime is difficult to settle in the lagoons because of its true colloidal nature, and the use of calcium sulfate or other electrolytes can promote coagulation, agglomeration, and settling of the particles. Usually an addition of calcium sulfate is unnecessary, because it is present in the wastewater from the sand-flotation process. Generally, it has been shown [33] that the clear effluent from the phosphate mining and beneficiation operation is not deleterious to fish life, but the occurrence of a dam break may result in adverse effects [19]. 

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. ... 

Hudarabine phosphate is a fluorinated nucleotide analog of the antiviral agent vidarabine. Its cytotoxicity is not well understood. It is rapidly dephospho-rylated at the cell membrane level and then rephos-phorylated intracellularly by deoxycytidine kinase to the active triphosphate derivative. It inhibits DNA polymerase and DNA primase. It is also incorporated into DNA and RNA. Hudarabine is administered intravenously by infusion over 30-120 min. It is eliminated by renal excretion with a terminal half life 10 hours. Adverse effects include myelosuppres-sion, nausea, vomiting, chills and fever. The number of CD4 positive cells is reduced and the incidence of opportunistic infections is increased. 

A variety of adverse effects have been reported following the use of antacids. If sodium bicarbonate is absorbed, it can cause systemic alkalization and sodium overload. Calcium carbonate may induce hypercalcemia and a rebound increase in gastric secretion secondary to the elevation in circulating calcium levels. Magnesium hydroxide may produce osmotic diarrhea, and the excessive absorption of Mg++ in patients with renal failure may result in central nervous system toxicity. Aluminum hydroxide is associated with constipation serum phosphate levels also may become depressed because of phosphate binding within the gut. The use of antacids in general may interfere with the absorption of a number of antibiotics and other medications. 

Canaline is a potent inhibitor of all seven pyridoxal phosphate-containing enzymes studied by Rahiala et (27) but it lacks adverse effects on three ornithine-utiTTzing enzymes lacking a Bg cofactor. Finally, in jack bean, Canavalia ensiformis, ornithine carbamoyl transferase can form 0-ureido-L-homoserine from canaline and carbamoyl phosphate as it does citrulline from ornithine and carbamoyl phosphate. Nevertheless, neither compound inhibited formation of the reaction products (31). 

Pralidoxime is administered by intravenous infusion, 1-2 g given over 15-30 minutes. In spite of the likelihood of aging of the phosphate-enzyme complex, recent reports suggest that administration of multiple doses of pralidoxime over several days may be useful in severe poisoning. In excessive doses, pralidoxime can induce neuromuscular weakness and other adverse effects. Pralidoxime is not recommended for the reversal of inhibition of acetylcholinesterase by carbamate inhibitors. Further details of treatment of anticholinesterase toxicity are given in Chapter 58. 

Gastrointestinal complaints (eg, nausea, diarrhea, vomiting, flatulence) are the most common adverse effects but rarely require discontinuation of therapy. Other potential adverse effects include headache and asthenia. Tenofbvir-associated proximal renal tubulopathy causes excessive renal phosphate and calcium losses and 1-hydroxylation defects of vitamin D, and preclinical studies in several animal species have demonstrated bone toxicity (eg, osteomalacia). Monitoring of bone mineral density should be considered with long-term use in those with risk factors for or with known osteoporosis, as well as in children. Reduction of renal function over time, as well as cases of acute renal failure and Fanconi s syndrome, have been reported in patients receiving tenofovir alone or in combination with emtricitabine. For this reason, tenofovir should be used with caution in patients at risk for renal dysfunction. Tenofovir may compete with other drugs that are actively secreted by the kidneys, such as cidofovir, acyclovir, and ganciclovir. 

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