Cal C Mal

Uses

Calcium is a mineral found in over-the-counter supplements or prescription formulations used for the treatment of specific medical conditions related to calcium deficiency.

Calcium plays a vital role in the anatomy, physiology and biochemistry of organisms and of the cell, particularly in signal transduction pathways. It is vital in cell signaling, muscular contractions, bone health, and signalling cascades.

Vitamin D is used to treat and prevent bone disorders (such as rickets, osteomalacia). Vitamin D is made by the body when skin is exposed to sunlight. Sunscreen, protective clothing, limited exposure to sunlight, dark skin, and age may prevent getting enough vitamin D from the sun.

Vitamin D with calcium is used to treat or prevent bone loss (osteoporosis). Vitamin D is also used with other medications to treat low levels of calcium or phosphate caused by certain disorders (such as hypoparathyroidism, pseudohypoparathyroidism, familial hypophosphatemia). It may be used in kidney disease to keep calcium levels normal and allow normal bone growth.

Cal C Mal is also used to associated treatment for these conditions: Calcium Deficiency, Deficiency, Vitamin D, Osteodystrophy, Osteomalacia, Osteoporosis, Chronic Hypocalcemia, Chronic Hypocalcemia caused by anticonvulsant medications, Care of the Joint, Mineral supplementation, Nutritional supplementationCalcium and Vitamin D Deficiencies, Deficiency of Vitamin D3, Deficiency, Vitamin A, Deficiency, Vitamin D, Fracture Bone, Hip Fracture, Hypoparathyroidism, Hypophosphatemia, Familial, Menopause, Osteomalacia, Osteoporosis, Postmenopausal Osteoporosis, Vertebral Fractures, Vitamin D Resistant Rickets, Vitamin Deficiency, Severe Bone Resorption, Spine fracture, Calcium supplementation, Nutritional supplementation, Vitamin D Supplementation, Vitamin supplementation

How Cal C Mal works

Calcium plays a vital role in the anatomy, physiology and biochemistry of organisms and of the cell, particularly in signal transduction pathways. More than 500 human proteins are known to bind or transport calcium. The skeleton acts as a major mineral storage site for the element and releases Ca2+ ions into the bloodstream under controlled conditions. Circulating calcium is either in the free, ionized form or bound to blood proteins such as serum albumin. Parathyroid hormone (secreted from the parathyroid gland) regulates the resorption of Ca2+ from bone. Calcitonin stimulates incorporation of calcium in bone, although this process is largely independent of calcitonin. Although calcium flow to and from the bone is neutral, about 5 mmol is turned over a day. Bone serves as an important storage point for calcium, as it contains 99% of the total body calcium. Low calcium intake may also be a risk factor in the development of osteoporosis. The best-absorbed form of calcium from a pill is a calcium salt like carbonate or phosphate. Calcium gluconate and calcium lactate are absorbed well by pregnant women. Seniors absorb calcium lactate, gluconate and citrate better unless they take their calcium supplement with a full breakfast. The currently recommended calcium intake is 1,500 milligrams per day for women not taking estrogen and 800 milligrams per day for women on estrogen. There is close to 300 milligrams of calcium in one cup of fluid milk. Calcium carbonate is currently the best and least expensive form of calcium supplement available.

Most individuals naturally generate adequate amounts of vitamin D through ordinary dietary intake of vitamin D (in some foods like eggs, fish, and cheese) and natural photochemical conversion of the vitamin D3 precursor 7-dehydrocholesterol in the skin via exposure to sunlight .

Conversely, vitamin D deficiency can often occur from a combination of insufficient exposure to sunlight, inadequate dietary intake of vitamin D, genetic defects with endogenous vitamin D receptor, or even severe liver or kidney disease . Such deficiency is known for resulting in conditions like rickets or osteomalacia, all of which reflect inadequate mineralization of bone, enhanced compensatory skeletal demineralization, resultant decreased calcium ion blood concentrations, and increases in the production and secretion of parathyroid hormone . Increases in parathyroid hormone stimulate the mobilization of skeletal calcium and the renal excretion of phosphorus . This enhanced mobilization of skeletal calcium leads towards porotic bone conditions .

Ordinarily, while vitamin D3 is made naturally via photochemical processes in the skin, both itself and vitamin D2 can be found in various food and pharmaceutical sources as dietary supplements. The principal biological function of vitamin D is the maintenance of normal levels of serum calcium and phosphorus in the bloodstream by enhancing the efficacy of the small intestine to absorb these minerals from the diet . At the liver, vitamin D3 or D2 is hydroxylated to 25-hydroxyvitamin D and then finally to the primary active metabolite 1,25-dihydroxyvitamin D in the kidney via further hydroxylation . This final metabolite binds to endogenous vitamin d receptors, which results in a variety of regulatory roles - including maintaining calcium balance, the regulation of parathyroid hormone, the promotion of the renal reabsorption of calcium, increased intestinal absorption of calcium and phosphorus, and increased calcium and phosphorus mobilization of calcium and phosphorus from bone to plasma to maintain balanced levels of each in bone and the plasma .

In particular, calcitriol interacts with vitamin D receptors in the small intestine to enhance the efficiency of intestinal calcium and phosphorous absorption from about 10-15% to 30-40% and 60% increased to 80%, respectively . Furthermore, calcitriol binds with vitamin D receptors in osteoblasts to stimulate a receptor activator of nuclear factor kB ligand (or RANKL) which subsequently interacts with receptor activator of nuclear factor kB (NFkB) on immature preosteoclasts, causing them to become mature bone-resorbing osteoclasts . Such mature osteoclasts ultimately function in removing calcium and phosphorus from bone to maintain blood calcium and phosphorus levels . Moreover, calcitriol also stimulates calcium reabsorption from the glomerular filtrate in the kidneys .

Additionally, it is believed that when calcitriol binds with nuclear vitamin D receptors, that this bound complex itself binds to retinoic acid X receptor (RXR) to generate a heterodimeric complex that consequently binds to specific nucleotide sequences in the DNA called vitamin D response elements . When bound, various transcription factors attach to this complex, resulting in either up or down-regulation of the associated gene's activity. It is thought that there may be as much as 200 to 2000 genes that possess vitamin D response elements or that are influenced indirectly to control a multitude of genes across the genome . It is in this way that cholecalciferol is believed to function in regulating gene transcription associated with cancer risk, autoimmune disorders, and cardiovascular disease linked to vitamin D deficiency . In fact, there has been some research to suggest calcitriol may also be able to prevent malignancies by inducing cellular maturation and inducing apoptosis and inhibiting angiogenesis, exhibit anti-inflammatory effects by inhibiting foam cell formation and promoting angiogenesis in endothelial colony-forming cells in vitro, inhibit immune reactions by enhancing the transcription of endogenous antibiotics like cathelicidin and regulate the activity and differentiation of CD4+ T cells, amongst a variety of other proposed actions .

Dosage

Cal C Mal dosage

Oral solution: Colecalciferol (Vitamin D3) is recommended 5-10 mcg or 1-2ml (200-400 IU)/day or as directed by the physician.

Chewable tablet: Cholecalciferol (Vitamin D3) is recommended 100 IU (1 tablet) daily, or as directed by physician. Take the medicine with food or within 1 hour after a meal. Place the tablet in mouth swallow after chewing.

Injection:

• Treatment of Cholecalciferol deficiency: 40,000 lU/week for 7 weeks, followed by maintenance therapy (1400-2000 lU/day). Follow-up 25 (OH) D measurements should be made approximately 3 to 4 months after initiating maintenance therapy to confirm that the target level has been achieved.
• Prevention of Vitamin D deficiency: 20,000 lU/Month.
• Treatment of Vitamin D deficiency:12-18 years: 20,000 IU, once every 2 weeks for 6 weeks. Prevention of Vitamin D deficiency, 12-18 years: 20,000 IU, once every 6 weeks.

Side Effects

Generally all nutritional supplements are considered to be safe and well tolerable. However, few side-effects can generally occur including hypercalcaemia syndrome or Calcium intoxication (depending on the severity and duration of hypercalcaemia), occasional acute symptoms include anorexia, headache, nausea, vomiting, abdominal pain or stomach ache and constipation with the administration of Colecaciferol.

Toxicity

Chronic or acute administration of excessive doses of cholecalciferol may lead to hypervitaminosis D, manifested by hypercalcemia and its sequelae . Early symptoms of hypercalcemia may include weakness, fatigue, somnolence, headache, anorexia, dry mouth, metallic taste, nausea, vomiting, vertigo, tinnitus, ataxia, and hypotonia . Later and possibly more serious manifestation include nephrocalcinosis, renal dysfunction, osteoporosis in adults, impaired growth in children, anemia, metastatic calcification, pancreatitis, generalized vascular calcification, and seizures .

Safety of doses in excess of 400 IU (10mcg) of vitamin D3 daily during pregnancy has not been established . Maternal hypercalcemia, possibly caused by excessive vitamin D intake during pregnancy, has been associated with hypercalcemia in neonates, which may lead to supravalvular aortic stenosis syndrome, the features of which may include retinopathy, mental or growth retardation, strabismus, and other effects . Hypercalcemia during pregnancy may also lead to suppression of parathyroid hormone release in the neonate, resulting in hypocalcemia, tetany, and seizures .

Vitamin D is deficient in maternal milk; therefore, breastfed infants may require supplementation. Use of excessive amounts of Vitamin D in nursing mothers may result in hypercalcemia in infants. Doses of Vitamin D3 in excess of 10 µg daily should not be administered daily to nursing women.

Precaution

People with the following conditions should exercise caution when considering taking vitamin D supplements: High blood Calcium or Phosphorus level, Heart problems, Kidney disease.

Vitamin D must be taken with adequate amounts of both Calcium and Magnesium supplementation. When Calcium level is low (due to insufficient vitamin D and calcium intake), the body activates the parathyroid gland, which produces PTH (parathyroid hormone). This hormone kick starts vitamin D hormone production and assists removal of Calcium from the bones to be used in more important functions such as neutralizing body acidity.

Interaction

Cholecalciferol is known to interact with Carbamazepine, Dactinomycin, Diuretics, Fosphenytoin, Miconazole, Phenobarbital, Phenytoin, Primidone

Volume of Distribution

Studies have determined that the mean central volume of distribution of administered cholecalciferol supplementation in a group of 49 kidney transplant patients was approximately 237 L .

Elimination Route

Cholecalciferol is readily absorbed from the small intestine if fat absorption is normal . Moreover, bile is necessary for absorption as well .

In particular, recent studies have determined aspects about the absorption of vitamin D, like the fact that a) the 25-hydroxyvitamin D metabolite of cholecalciferol is absorbed to a greater extent than the nonhydroxy form of cholecalciferol, b) the quantity of fat with which cholecalciferol is ingested does not appear to largely affect its bioavailability, and c) age does not apparently effect vitamin D cholecalciferol .

Half Life

At this time, there have been resources that document the half-life of cholecalciferol as being about 50 days while other sources have noted that the half-life of calcitriol (1,25-dihydroxyvitamin D3) is approximately 15 hours while that of calcidiol (25-hydroxyvitamin D3) is about 15 days .

Moreover, it appears that the half-lives of any particular administration of vitamin d can vary due to variations in vitamin d binding protein concentrations and genotype in particular individuals .

Clearance

Studies have determined that the mean clearance value of administered cholecalciferol supplementation in a group of 49 kidney transplant patients was approximately 2.5 L/day .

Elimination Route

The kidney excretes 250 mmol a day in urine, and resorbs 245 mmol, leading to a net loss in the urine of 5 mmol/d.

It has been observed that administered cholecalciferol and its metabolites are excreted primarily in the bile and feces .

Pregnancy & Breastfeeding use

There is no evidence to suggest that vitamin D is teratogenic in humans even at very high doses. Colecalciferol should be used during pregnancy only if the benefits outweigh the potential risk to the fetus.

It should be assumed that exogenous Colecalciferol passes into the breast milk. In view of the potential for hypercalcaemia in the mother and for adverse reactions from Colecalciferol in nursing infants, mothers may breastfeed while taking Colecalciferol, provided that the serum Calcium levels of the mother and infant are monitored.

Contraindication

Colecalciferol is contraindicated in all diseases associated with hypercalcaemia. It is also contraindicated in patients with known hypersensitivity to Colecalciferol (or medicines of the same class) and any of the constituent excipients. Colecalciferol is contraindicated if there is evidence of vitamin D toxicity.

Acute Overdose

Symptoms: anorexia, headache, vomiting, constipation, dystrophy (weakness, loss of weight), sensory disturbances, possibly fever with thirst, polyuria, dehydration, apathy, arrested growth and urinary tract infections. Hypercalcaemia ensues, with metastatic calcification of the renal cortex, myocardium, lungs and pancreas.

Treatment: Immediate gastric lavage or induction of vomiting to prevent further absorption. Liquid paraffin should be administered to promote faecal excretion. Repeated serum calcium determinations are advisable. If elevated calcium levels persist in the serum, phosphates and corticosteroids may be administered and measures instituted to bring about adequate diuresis.

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