Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020437 (hypercalcemia)
 10,293 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intact parathyroid hormone (PTH) was analysed in 1107 samples over a 13 month period. Of these, 181 samples (16%) gave results of < or = 1 pmol/L and the case notes of 169 of these 181 patients were examined. Eighty-two patients (48%) were hypercalcaemic at the time of the PTH assay. As expected, the most common diagnosis in this group was hypercalcaemia of malignancy but surprisingly this accounted for only 42 of the hypercalcaemic patients; an unexpectedly high proportion (20 patients) had chronic renal failure with hypercalcaemia due to excessive treatment with 1 alpha-hydroxycholecalciferol; eight patients had transient unexplained hypercalcemia and the remaining 12 patients were hypercalcaemic for a variety of causes including immobilization, bendrofluazide treatment and Paget's disease. Fifty-nine patients (35%) were normocalcaemic: 26 had osteoporosis, 10 had chronic renal failure and the remainder had a wide range of diagnoses. It is possible that the low intact PTH result in a proportion of the normocalcaemic group was caused by ingestion of calcium tablets prior to blood sampling for PTH. Twenty-eight patients (17%) were hypocalcaemic: 24 of these had hypoparathyroidism, two had chronic renal failure and two had transient unexplained hypocalcaemia.
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PMID:A survey of diagnoses in patients with a low intact parathyroid hormone concentration. 851 6

Salmon calcitonin (sCT) is a therapeutic peptide used in the treatment of Paget's Disease, postmenopausal osteoporosis, and hypercalcemia due to malignancy. In this study, recombinant sCT (rsCT) was administered intravenously (iv), subcutaneously (sc), and intraduodenally (id.) in rats to evaluate pharmacodynamic (PD) response as a measure of rsCT bioavailability (F) and to test the feasibility of delivering rsCT orally. rsCT pharmacokinetics were linear throughout the range of iv and sc doses studied. Following sc administration, F ranged from 11.2% to 23.1% and was linear. The absorption of rsCT after id. administration was low (0.022%); however, a significant lowering of serum calcium concentrations was observed. Serum calcium lowering was nonlinear and saturable after sc administration with the minimum dose required for maximum calcium lowering (Dmin/max) equal to 10.2 ng and a maximal response of 426.8 mg min/dL. Using Dmin/max as the reference dose, absolute Fs were recalculated using PD response after id. administration of 1 and 2 mg of rsCT and were 0.040% and 0.029%, respectively. Substantial overestimates of F were obtained when the reference dose was not properly selected. While the absorption of rsCT was low, the significant lowering of serum calcium levels suggests that oral delivery of sCT is feasible. The results of these studies also suggest that PD response is useful in assessing the oral bioavailability of peptides; however, when PD response is saturable, as is the case for rsCT, the reference dose should be carefully selected in order to avoid overestimates of F.
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PMID:Utility of pharmacodynamic measures for assessing the oral bioavailability of peptides. 1. Administration of recombinant salmon calcitonin in rats. 858 58

Intravenous pamidronate disodium has been used successfully in the treatment of malignancy-associated hypercalcemia and Paget's disease of bone. Although the definitive treatment of primary hyperparathyroidism (PHPT) is surgical, intravenous pamidronate has been used to treat hypercalcemia of PHPT when surgery was contraindicated. We report two cases of PHPT in which intravenous pamidronate effectively reduced hypercalcemia and significantly improved the clinical symptoms. The results of our study and the experience in the literature suggest that pamidronate is a safe and effective method of reducing serum calcium in patients with PHPT when definitive surgery is contraindicated or must be postponed.
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PMID:Intravenous pamidronate for hypercalcemia of primary hyperparathyroidism. 863 11

The bisphosphonates are a class of synthetic compounds used in the treatment of various metabolic bone diseases, including hypercalcaemia of malignancy, Paget's disease, postmenopausal osteoporosis and corticosteroid-induced bone loss. Although there have been numerous studies comparing first, second and third generation bisphosphonates with placebo, there has been a paucity of comparative research investigating the effectiveness of these substances with other pharmacological agents. Still, the available evidence indicates that the bisphosphonates are well tolerated and effective therapeutic agents for various metabolic bone diseases. It seems certain that within the next 5 years, this class of drugs will emerge as one of the foremost options for treating Paget's disease and osteoporosis.
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PMID:Comparative clinical pharmacology and therapeutic use of bisphosphonates in metabolic bone diseases. 870 93

Elcatonin, used for treatment of hypercalcaemia, Paget's disease and osteoporosis, causes flushing of the face and hands. To determine whether this was because of increased levels of vasoactive intestinal peptide, which is known to induce vasodilation, the effect of elcatonin on the plasma levels of vasoactive intestinal peptide was studied in five healthy volunteers. After a single intramuscular administration of elcatonin (20 int units), peak plasma elcatonin levels (approx. 30 pg mL-1) were achieved 30 min after injection. Plasma vasoactive intestinal peptide concentrations rose similarly with peak levels of about 17 pg mL-1 after 30 min. Side-effects such as cutaneous flushing (most obvious in the face and hands) occurred to an extent dependent on the amount of elcatonin administered, and declined over 45 min in parallel with the fate of plasma vasoactive intestinal peptide. The side-effects of elcatonin, especially cutaneous flushing, seem to be closely connected with vasoactive intestinal peptide.
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PMID:Elcatonin raises levels of vasoactive intestinal peptide in human plasma. 883 4

Recognition of the way in which naturally occurring pyrophosphate affects bone metabolism has stimulated the development of a whole series of related compounds, the bisphosphonates. Although the precise mechanism of action of these compounds remains incompletely understood, they have been proven profoundly effective in clinical practice and already constitute a major advance in the therapy of conditions characterised by excessive bone resorption. Serious adverse effects are rare; however, mineralisation problems are a concern, particularly with etidronate. The reduction in bone turnover during prolonged treatment for osteoporosis is also a concern but as yet of uncertain clinical importance. The wide variation in potency of different bisphosphonates in inhibiting the resorption, mineralisation and turnover of bone will increasingly determine which agents are used in various clinical situations. Bisphosphonates are the treatment of choice in Paget's disease and hypercalcaemia of malignancy. They also appear to have potential to alter the course of metastatic bony disease, although the magnitude and clinical importance of any such effect remains unclear. Bisphosphonates show promise in the prevention and treatment of osteoporosis and increase bone mass in postmenopausal and steroid-induced osteoporosis. The effects of these drugs in other situations are less clear and the effects on fracture rates are not yet fully characterised. Optimal regimens have yet to be established but the long half-lives of these agents makes intermittent treatment a rational and convenient approach.
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PMID:Bisphosphonates and the treatment of bone disease in the elderly. 884 85

The bisphosphonates (formerly known as diphosphonates) constitute a recently developed class of drugs for use in a variety of diseases of bone and calcium metabolism. Developed in the past three decades, only a few compounds of this large family of drugs are now commercially available for various therapeutic indications that vary broadly, from country to country. The clinical use of bisphosphonates is based on their ability to inhibit bone resorption. Thus, their main indications concern diseases with high bone remodeling, such as Paget's disease of bone, osteoporosis, metastatic bone diseases, and malignant and nonmalignant hypercalcemia. Their other main action is to inhibit bone formation; the ratio of inhibition of bone resorption to inhibition of bone formation varies according to the compounds. This ratio is less favorable for the first available bisphosphonates, such as etidronate. New bisphosphonates are more and more potent and possess a safer ratio. With their increasing power, there could be some risk of freezing bone remodeling, but so far this fearful complication has not yet been observed.
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PMID:Clinical use of bisphosphonates. 886 93

Bisphosphonates are widely used in disorders associated with increased resorption of bone, particularly in Paget's disease of bone and the hypercalcaemia of malignancy. Their undoubted efficacy and relatively low toxicity makes them attractive candidates for the management of osteoporosis. The three bisphosphonates widely tested are etidronate, pamidronate and clodronate. Whereas pamidronate can only be given by intravenous infusion, clodronate may be given intravenously or by mouth. Unlike etidronate, even high doses of clodronate do not impair the mineralisation of bone, making it suitable for long-term use in osteoporosis. Clodronate has been shown to inhibit experimentally induced increases in bone resorption and in patients prevents bone loss at the menopause and during immobilisation. Short-term and long-term studies indicate that clodronate appears to stop bone loss at the lumbar spine in patients with vertebral osteoporosis. Long-term studies of the effects at the hip are not yet reported. The effects of clodronate on the frequency of osteoporotic fractures are not yet known and will demand well controlled long-term prospective studies.
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PMID:Clodronate and osteoporosis. 886 46

Oral pamidronate (APD) at high doses (400-900 mg/day) is employed as antiresorptive agent for the treatment of Paget's disease. In some occasions hypocalcemia may occur, and is interpreted as a relative overdosage. To avoid this complication and the consequent PTH release, supplementation with calcium salts is recommended. In osteoporotic syndromes, APD is prescribed at a lower dosage (200 mg/day) and currently calcium or vitamin D are also systematically added. But at this low dose the antiresorptive activity is partial and transient. In order to observe the effects on calcemia of multiple therapy, data from 129 postmenopausal women with the diagnosis of osteopenia or osteoporosis treated with 200 mg/day of APD soft capsules during 6-10 months, were gathered retrospectively. The first group (n: 13) received APD alone; the second group was supplemented with 1 g/day calcium salts (n: 61); the third group received 0.015-0.025 mg/day vitamina D (n: 10); and the fourth received both calcium plus vitamin D (n: 45). In samples of 24 h, urine, calcium, creatinine, hydroxyproline, and serum total calcium were measured before and after therapy. No hypocalcemia was detected. All groups, except the one treated with APD alone, showed a significant trend to increase their calcemia values between normal ranges (Table 1, 2). Only in one patient treated with APD + Ca + vitamin D, hypercalcemia was detected. Measuring HOP/Cr and Ca/Cr in urine as resorption markers, showed that 27% of the APD + Ca group and 33% of the APD + Ca + vitamin D group showed scant or any repercussion on mentioned resorption indexes, meaning that the response to APD could be hindered in those cases. In conclusion, while using low doses of oral APD, calcium salts should not be systematically recommended. There is no trend to hypocalcemia. Furthermore, calcium salts may favor drug interactions and so induce digestive side effects or poor responses. Calcium supplementation should be prescribed only on the basis of low calcium diet and not to prevent APD collateral effects on calcemia.
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PMID:[Effect of low doses of oral pamidronate (APD) on the calcemia of osteopenic or osteoporotic patients]. 893 64

The calcitonin gene peptide superfamily consists of calcitonin (CT), calcitonin gene-related peptide (CGRP), and amylin. CT and CGRP derive from the CT/CGRP gene, which is encoded on chromosome 11. Alternative splicing of the primary RNA transcript leads to the translation of CGRP and CT peptides in a tissue-specific manner. CGRP (a 37-amino-acid neuropeptide) and its receptors are widely distributed in the body, and it is the most potent endogenous vasodilatory peptide discovered so far. CT (a 32-amino-acid peptide) is, however, a hormone primarily involved in protecting the skeleton during periods of "calcium stress" such as growth, pregnancy, and lactation. CT derives from the C cells of the thyroid gland and is the most potent peptide inhibitor of osteoclast-mediated bone resorption. Therefore, treatment with CT is highly effective for conditions associated with increased bone turnover such as Paget's disease, osteoporosis, Sudeck's atrophy, and hypercalcemia. Amylin (a 37-amino-acid peptide) is generated from a gene located on chromosome 12 (thought to be an evolutionary duplication of chromosome 11) and shares 46% amino acid sequence homology with CGRP and 20% with human CT. Amylin is predominantly located in the beta cells of the islets of the pancreas and may be involved in the pathogenesis of type II diabetes by deposition as amyloid within the pancreas, leading to beta cell destruction. Adrenomedullin, a recently discovered 52-amino-acid vasoactive peptide from adrenal tissue, shares 24% homology with CGRP and is also a member of this superfamily of peptides. A portion of the B-chain of insulin is strongly homologous to these four peptides. Not only does adrenomedullin (13-52) show 24% amino acid homology with CGRP, it also has a biological activity profile similar to that of CGRP.CGRP, CT, and amylin are related to the insulin gene superfamily of peptides, which may all have diverged from a common ancestral gene during evolution. When the crystallographic- and nuclear magnetic resonance-based molecular modeling of the three-dimensional structure of CGRP, CT, amylin, and adrenomedullin peptides and their receptors is available, it will lead to a greater understanding of the involvement of this family of peptides in pathophysiology. Together, CGRP, CT, amylin and adrenomedullin have overlapping biological effects owing to their structures and cross-reactivity between receptors. I propose that CT, CGRP, adrenomedullin, and amylin belong to a family of G-protein-coupled receptors (an "insulin superfamily" of peptides) and therefore share some of the characteristics of insulin, such as growth factor-like effects, and possible interaction at insulin receptor sites as an antagonist.
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PMID:Amylin, calcitonin gene-related peptide, calcitonin, and adrenomedullin: a peptide superfamily. 920 29


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