Phosphate, absorption plasma concentration

Disopyr mide. Disopyramide phosphate, a phenylacetamide analogue, is a racemic mixture. The dmg can be adininistered po or iv and is useful in the treatment of ventricular and supraventricular arrhythmias (1,2). After po administration, absorption is rapid and nearly complete (83%). Binding to plasma protein is concentration-dependent (35—95%), but at therapeutic concentrations of 2—4 lg/mL, about 50% is protein-bound. Peak plasma concentrations are achieved in 0.5—3 h. The dmg is metabolized in the fiver to a mono-AJ-dealkylated product that has antiarrhythmic activity. The elimination half-life of the dmg is 4—10 h. About 80% of the dose is excreted by the kidneys, 50% is unchanged and 50% as metabolites 15% is excreted into the bile (1,2). 

PTH is secreted from the parathyroid glands in response to a low plasma concentration of ionized (free) calcium. PTH immediately causes the transfer of labile calcium stores from bone into the bloodstream. PTH increases rates of dietary calcium absorption by the intestine indirectly via the vitamin D3 system activation of enterocyte activity. Within the kidney, PTH directly stimulates calcium reabsorption and a phosphate diuresis. 

After oral administration peak plasma concentration of phenytoin usually takes 2 to 4 hours with a second peak at 10 to 12 hours. When administered intramuscularly, pheny-toin is eventually absorbed completely, the drug first crystallises out at the injection site and then slowly redissolves in tissue fluids before entering into the circulation. As a result absorption of phenytoin by IM route is too slow to produce a reliable effect. In contrast a phosphate prodrug, fosphenytoin, is more soluble and is well absorbed after IM administration. 

ESTRAMUSTINE CALCIUM AND DAIRY PRODUCTS i plasma concentrations of estramustine and risk of poor therapeutic response Due to l absorption of estramustine owing to the formation of a calcium-phosphate complex Administer estramustine 1 hour before or 2 hours after dairy products or calcium supplements... 

Erythromycin formulations are highly irritant if administered by i.m. injection and are not used in horses. Many p.o. preparations of erythromycin are enteric coated to allow passage into the small intestine, where absorption is higher because of the higher pH. In horses, erythromycin stearate and erythromycin phosphate produce peak plasma concentrations faster than the ester formulations following p.o. administration. 

A wide range of plasma phosphorus concentration has been observed by other workers in primary hyperparathyroidism (C7) and explained in terms of diet and renal excretion. Unlike the calcium concentration, which is normally very constant regardless of dietary intake and urinary excretion, the concentration of inorganic phosphate in plasma is the resultant of the rate of phosphorus absorption from the gut and protein catabolism, on the one hand, and of renal excretion, on the other. Although the parathyroid hormone promotes phosphorus excretion, this is only one of the factors governing plasma phosphate concentration. Plasma phosphate in cases of hyperparathyroidism on a relatively high phosphorus intake may therefore not be distinguishable from that in normal subjects on a lower intake. 

ABSORPTION, DISTRIBUTION, AND EXCRETION Phosphate is a component of many foods thus, dietary insufficiency rarely causes phosphate depletion. Intestinal uptake of phosphate primarily is passive, although an active component is stimulated by several factors, including vitamin D. In adults, about two-thirds of ingested phosphate is absorbed, almost all of which is excreted into the urine. In children, phosphate balance is positive and the plasma concentration of phosphate is higher than in adults. 

Effects on Kidney In the kidney, PTH enhances the efficiency of Ca reabsorption, inhibits tubular reabsorption of phosphate, and stimulates conversion of 25-OHD to calcitriol (Figure 61-3, see below). As a result, filtered Ca + is avidly retained and its plasma concentration increases, whereas phosphate is excreted and its plasma concentration falls. Newly synthesized calcitriol interacts with specific high-affinity vitamin D receptors (VDRs) in the intestine to increase the efficiency of calcium absorption, thereby also increasing the plasma Ca concentration. 

If vitamin D has no effect on calcium absorption, it does affect calcium mobilization and thereby restores plasma concentrations of calcium. This finding explains why vitamin D deficiency was associated with hypocalcemia. The effect on the bone seems to require a synergetic action of vitamin D and parathormone. The 1,25-hydroxylated derivative seems to be the major active compound causing calcium release from the bone. The 25-hydroxyl derivative has, however, been shown to be active as well. Finally, vitamin D increases renal proximal tubular reabsorption of phosphate in normal and vitamin D deficient animals. Consequently phosphate excretion is decreased. Inasmuch as this effect occurs in parathyroidectomized animals, the effect of vitamin D or its metabolites must be direct. Again, the active metabolites are the 25 and 1,25-hydroxy derivatives. A calcium binding protein has been isolated from the kidney cortex, but its role in renal reabsorption is not known. 

Vitamin D hormone is derived from vitamin D (cholecalciferol). Vitamin D can also be produced in the body it is formed in the skin from dehydrocholesterol during irradiation with UV light. When there is lack of solar radiation, dietary intake becomes essential, cod liver oil being a rich source. Metaboli-cally active vitamin D hormone results from two successive hydroxylations in the liver at position 25 ( calcifediol) and in the kidney at position 1 ( calci-triol = vit. D hormone). 1-Hydroxylation depends on the level of calcium homeostasis and is stimulated by parathormone and a fall in plasma levels of Ca or phosphate. Vit D hormone promotes enteral absorption and renal reabsorption of Ca and phosphate. As a result of the increased Ca + and phosphate concentration in blood, there is an increased tendency for these ions to be deposited in bone in the form of hydroxyapatite crystals. In vit D deficiency, bone mineralization is inadequate (rickets, osteomalacia). Therapeutic Liillmann, Color Atlas of Pharmacology... 

The major location of calcium in the body is in the skeleton, which contains more than 90% of the body calcium as phosphate and carbonate. Bone resorption and formation keeps this calcium in dynamic equilibrium with ionized and complexed calcium in blood, cellular fluids and membranes. Homeostasis is mainly regulated by the parathyroid hormone and vitamin D which lead to increased blood calcium levels, and by a thyroid hormone, calcitonin, which controls the plasma calcium concentration J5 Increasing the concentration of calcitonin decreases the blood calcium level, hence injections of calcitonin are used to treat severe hyperalcaemia arising from hyperparathyroidism, vitamin D intoxication or the injection of too high a level of parathyroid extract. High levels of calcitonin also decrease resorption of calcium from bone. Hypocalcaemia stimulates parathyroid activity, leading to increased release of calcium from bone, reduction in urinary excretion of calcium and increased absorption of calcium from the intestine. Urinary excretion of phosphate is enhanced. 

Action on the plasma membrane is the first and most fundamental of the bewildering array of deleterious effects of the cinnamic and benzoic acids. They reduce the transmembrane electrochemical potential with the immediacy and extent of that action depending on the concentration and lipid solubility of the compound.35,37,45,60 Rate of uptake also is concentration and pH-dependent, with transfer into and across the membrane greatest with lower pH conditions and higher external concentrations.60 Phenolic acid-induced depolarization of membranes causes a nonspecific efflux of both anions and cations accompanying the increased cell membrane permeability, and these membrane effects correlate with an inhibition of ion uptake. The phenolic acids suppress absorption of phosphate, potassium, nitrate, and magnesium ions, and overall changes in tissue... 

Hydrocortisone is readily absorbed from the gastrointestinal tract, and peak blood concentrations are attained in about 1 h. The plasma half-life is about 100 min, and hydrocortisone is more than 90% bound to plasma proteins. Following intramuscular injection, absorption of the water-soluble sodium phosphate and sodium succinate ester is rapid, whilst absorption of free alcohol or lipid-soluble esters is slower. 

Q4 The parathyroids produce a peptide hormone, PTH, which controls the level of calcium in the body. A sensor on the surface of the parathyroid cells monitors blood calcium concentration and PTH is secreted in response to a fall in plasma calcium ion concentration. An increase in the level of PTH leads to hypercalcaemia (raised blood calcium) conversely, a reduction in the level of PTH leads to hypocalcaemia. PTH acts on the kidney to reduce reabsorption of phosphate and at the same time to increase reabsorption of calcium. In addition, it promotes the release of calcium and phosphate into the blood by activating osteoclasts, which break down the inorganic matrix of bone. PTH also increases the absorption of calcium by the mucosal cells of the intestine. The latter is a rather slow, indirect action mediated by PTH stimulation of calcitriol secretion by the kidney. 

Bone contains nearly all of the calcium (99%), most of the phosphate (85%), and much of the magnesium (55%) of the body. The concentrations of calcium, phosphate, and magnesium in plasma are dependent on the net effect of bone mineral deposition and resorption, intestinal absorption, and renal excretion. PTH and 1,25-dihydroxyvitamin D are the principal hormones regulating these three processes. 

When plasma Ca + rises, PTH secretion is suppressed and tubular Ca reabsorption decreases. The reduced PTH promotes renal phosphate conservation, and both the decreased PTH and the increased phosphate reduce calcitriol production and thereby decrease intestinal Ca absorption. Finally, bone remodeling is suppressed. These physiological events provide an integrated response to positive or negative excursions of plasma Ca concentration. 

VITAMIN D DEFICIENCY Vitamin D deficiency is associated with inadequate absorption of calcium and phosphate. The resulting decrease in Ca stimulates PTH secretion, which acts to restore plasma Ca + at the expense of bone. Plasma phosphate concentration will remain low due to the phosphaturic effect of PTH. In children, the failure to mineralize newly formed bone results in rickets, a growth disorder in which the long bones may be bowed due to inadequate calcification. 

The work of Harrison and Harrison (1941) is best discussed in connection with the tabulated data on metabolic studies in children (Table I). The following quotation from Harrison and Harrison is instructive Careful examination of the data from metabolic studies in the rachitic infant leads to the conclusion that deficient absorption of phosphate from the intestinal tract cannot wholly explain the diminished concentration of phosphate in the plasma. In infants developing rickets on a cow s milk diet high in both calcium and phosphate, the amount of phosphate absorbed from the intestinal tract would be sufficient for the needs of the infant were the phosphate retained rather than excreted in the urine. ... 

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