Plasma, calcium concentrations

Magnesium. In the adult human, 50—70% of the magnesium is in the bones associated with calcium and phosphoms. The rest is widely distributed in the soft tissues and body duids. Most of the nonbone Mg ", like K", is located in the intracellular duid where it is the most abundant divalent cation. Magnesium ion is efftcientiy retained by the kidney when the plasma concentration of Mg fads in this respect it resembles Na". The functions of Na", K", Mg ", and Ca " are interrelated so that a deficiencv of Mg " affects the metaboHsm of the other three ions (26). Foods rich in magnesium are listed in Table 9. 

Calcitonin is secreted when abnormally high calcium levels occur in plasma. Although plasma concentrations are normally minute (<100 pg/mL), they increase two- to threefold after calcium infusion. Calcitonin has a short plasma half-life (ca 10 min). Certain thyroid tumors are the result of CT concentrations 50—500 times normal. The mechanism of action is a direct inhibition of bone resorption. Calcitonin is used clinically in various diseases in which hypercalcemia is present, eg, Paget s disease (46). 

Bames, D.W.H., Bishop, M., Harrison, G.E. and Sutton, A. 1961 Comparison of the plasma concentration and urinary excretion of strontium and calcium in man. InternationalJournal of Radiation Biology 3 637-646. 

The biosynthesis of PTH and its subsequent secretion are regulated by the plasma ionized calcium (Ca ) concentration through a complex process. An acute decrease of Ca " results in a marked increase of PTH... 

The biphasic effect of divalent cations such as calcium on APTT is well recognized. Thus, whereas the addition of 0.025 M calcium chloride to citrated plasma has no effect on the APTT result, both higher and lower calcium chloride concentrations such as 0.065 or 0.004 M can artifactually elevate the APTT result (100). 

BPH—benign prostatic hypertrophy BPM—breaths per minute beats per minute BUN—blood urea nitrogen C—mean plasma concentration Cmi]X—maximum plasma concentration Cmm—minimum plasma concentration C albicans—Candida albicans C. bofulinum—Clostridium frotu/irtum C. difficile—Clostridium difficile C. jejuni—Campylobacter jejuni C. neoformans—Cryptococcus neoformans Ca—calcium... 

Some idea of the rate of absorption can be obtained from examination of the plasma concentration-time profile. It should be remembered, however, that the time to maximum plasma concentration Y ) is not when absorption is complete but when the rates of drug absorption and elimination are equal. Thus two drugs with the same absorption rate will differ in /max if elimination rates differ. Assessment of the rate of absorption can also be confounded by complex or slow drug distribution. For example, the calcium-channel blocker amlodipine has a much later /max than other similar drugs. This is not due to slow absorption but to partitioning in the liver membrane with slow redistribution. A quantitative assessment of the rate of absorption can be obtained by deconvolution of plasma profiles following IV and oral administration. 

There seems to be no metabolic control exerted on hepatic 25-hydroxylase and so all of the available cholecalciferol is converted. Hydroxylation in the kidney however is an important control point being regulated by PTH, and indirectly therefore by calcium and phosphate concentrations. Stimulation of la-hydroxylase by PTH is via a cyclic AMP (cAMP) -dependent mechanism and longer-term regulation of the activity of this enzyme is via induction mediated by other hormones such as oestrogens, cortisol and growth hormone. Typically, the plasma concentration of 1,25 dihydroxy vitamin D is in the range 20-60 ng/1, that is approximately 1000-times lower than that of its precursor. 

There are occasional anomalies to the rule that food reduces and delays peak plasma concentration. The anti-fungal drug, griseofulvin, has enhanced absorption if taken with a meal - possibly because it becomes emulsified by bile salts and passes more readily into the lymphatic drainage of the gut which bypasses the liver, entering the venous system directly. The immuno-suppressant cyclosporin, and calcium salts in general, show a similar increase in absorption when taken with a fatty meal. 

Magnesium sulfate, applied intravenously is often used as tocolytic. The mechanism of action is not completely clear but might involve a competition with calcium on the cellular level. Precautions in the sense of magnesium plasma level monitoring must be taken in patients with renal insufficiency since this divalent kation is eliminated by the kidneys. Relatively high plasma concentrations are necessary to achieve a sufficient tocolysis. The relatively frequent side effects are respiratory depression, depressed reflexes, headaches, palpitation and skin flushing in the mother and muscle relaxation and, rarely, CNS depression in the fetus. 

Drugs that have been associated with elevations in quinidine concentrations include acetazolamide, the antacids magnesium hydroxide and calcium carbonate, and the H2-receptor antagonist cimetidine. Cimetidine inhibits the hepatic metabolism of quinidine. Phenytoin, rifampin, and barbiturates increase the hepatic metabolism of quinidine and reduce its plasma concentrations. 

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. 

Mibefradil, a calcium channel blocker, is not toxic when used alone for cardiovascular treatment but on the market it was found to interact with at least 25 other drugs, resulting in increased plasma concentrations and consequently, toxicity. This example was one that increased regulatory focus on drug-drug interactions but only common interactions can be researched premarketing and the commonality of multiple polytherapy, for example in the elderly, cannot be fully legislated. 

When the calcium ion concentration is lowered in the fluids bathing nerve axons ifluids which are in very rapid equilibrium with the blood plasma) the electrical resistance ol the axon membrane is lowered, there is increased movement of sodium ions to ihe inside, and the ability ol ihe nerve to return io iis normal siale fallowing a discharge is slowed. Thus, on the one hand, there is hyperexcitabilily. Bui. the ability lor synaptic transmission is inhihited because the rate of acetylcholine liberation is a function ot ihe calcium ion concentration. The neuromuscular junction is... 

The adverse effects of atazanavir include fever, jaundice/scleral icterus, myalgia and diarrhea. Its coadministration is not recommended with the drugs that induce cytochrome P-450 isoenzyme CYP3A4. Ritonavir increases plasma concentrations of atazanavir. It is an inhibitor of isoenzymes CYP3A4, CYP2C8 and UGT1A1. The coadministration of atazanavir with calcium channel blockers, HMG-CoA reductase inhibitors, immunosuppressants and phosphodiesterase 5 inhibitors should be carefully monitored. 

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. 

CALCIUM CHANNEL BLOCKERS MACROLIDES t plasma concentrations of felodipine when co-administered with erythromycin cases of adverse effects of verapamil (bradycardia and 1 BP) with both erythromycin and clarithromycin Erythromycin inhibits CYP3A4-mediated metabolism of felodipine and verapamil. Clarithromycin and erythromycin inhibit intestinal P-gp, which may t the bioavailability of verapamil Monitor PR and BP closely watch for bradycardia and 1 BP. Consider reducing the dose of calcium channel blocker during macrolide therapy... 

CALCIUM CHANNEL BLOCKERS RIFAMPICIN Plasma concentrations of calcium channel blockers may be 1 by rifampicin Rifampicin induces CYP3A4-mediated metabolism of calcium channel blockers. It also induces CYP2C9-mediated metabolism of verapamil and induces intestinal P-gp, which may 1 the bioavailability of verapamil Monitor BP closely watch for 1 effect of calcium channel blockers... 

CALCIUM CHANNEL BLOCKERS BUSULFAN t plasma concentrations of busulfan and t risk of toxicity of busulfan such as veno-ocdusive disease and pulmonary fibrosis, when co-administered with diltiazem, nifedipine or verapamil Due to inhibition of CYP3A4-mediated metabolism of busulfan by these calcium channel blockers. Busulfan clearance may be l by 25%, and the AUC of busulfan may t by 1500 p,mol/L Monitor clinically for veno-ocdusive disease and pulmonary toxicity in transplant patients. Monitor busulfan blood levels as AUC of below 1500 p,mol/L per minute tends to prevent toxicity... 

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