Puspabio Kids

Uses

Calcium Gluconate is used for Antidote in severe hypermagnesaemia, Severe hyperkalaemia, Hypocalcaemic tetany, Severe acute hypocalcaemia, Hypocalcaemia and calcium deficiency states

Fish oil is a source of essential fatty acids used as a source of calories in parenteral nutrition and as a dietary supplement.

Under FDA approval, fish oil pharmaceuticals are typically products consisting of a combination of the omega-3-fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and are indicated primarily as an adjunct to diet to reduce triglyceride levels in adult patients with severe (>=500 mg/dL) hypertriglyceridemia .

Under EMA approval, such fish oil pharmaceuticals comprised of virtually the same fish and fish oil derived omega-3-fatty acids EPA and DHA are indicated specifically for (a) adjuvant treatment in secondary prevention after myocardial infarction, in addition to other standard therapy (ie. statins, antiplatelet medicinal products, beta blockers, ACE inhibitors), and (b) as a supplement to diet when dietary measures alone are insufficient to produce an adequate response, particularly with type IV hypertriglyceridemia in monotherapy or type IIb/III in combination with statins, when control of triglycerides is insufficient . In addition, prescribing information for EMA approved fish oil pharmaceuticals are also indicated as an adjunct to diet to reduce very high (>=500 mg/dL) triglyceride levels in adult patients, much like similar FDA approved indications .

Vitamin D is an ingredient found in a variety of supplements and vitamins.

Vitamin D is indicated for use in the treatment of hypoparathyroidism, refractory rickets (also known as vitamin D resistant rickets), and familial hypophosphatemia .

Puspabio Kids is also used to associated treatment for these conditions: Bone and tooth decay, Bone and tooth growth, Calcium Deficiency, Hypocalcemia, Nutritional Rickets, Osteomalacia, Osteoporosis, Otospongiosis, Postmenopausal Osteoporosis, Vitamin D Insufficiency, Vitamin D Resistant RicketsDietary and Nutritional Therapies, Nutritional supplementation, Parenteral NutritionDeficiency, Vitamin D

How Puspabio Kids works

Calcium is essential for the functional integrity of the nervous, muscular, and skeletal systems. It plays a role in normal cardiac function, renal function, respiration, blood coagulation, and cell membrane and capillary permeability. Also, calcium helps to regulate the release and storage of neurotransmitters and hormones, the uptake and binding of amino acids, absorption of vitamin B 12, and gastrin secretion. The major fraction (99%) of calcium is in the skeletal structure primarily as hydroxyapatite, Ca 10(PO 4) 6(OH) 2; small amounts of calcium carbonate and amorphous calcium phosphates are also present. The calcium of bone is in a constant exchange with the calcium of plasma. Since the metabolic functions of calcium are essential for life, when there is a disturbance in the calcium balance because of dietary deficiency or other causes, the stores of calcium in bone may be depleted to fill the body's more acute needs. Therefore, on a chronic basis, normal mineralization of bone depends on adequate amounts of total body calcium.

The specific mechanism of action by which the fish oil EPA and DHA acids are capable of reducing serum triglyceride levels is not yet fully understood . Nevertheless, it is proposed that such omega-3-fatty acids may not be the preferred substrates of the enzyme diacylglycerol O-acyltransferase that participates in the generation of triglycerides; that they might interact with nuclear transcription factors that manage lipogenesis; or that their presence and increase in levels can cause cellular metabolism to subsequently shift toward a decrease in triglyceride synthesis and an increase in fatty acid oxidation . Moreover, the EPA and DHA acids are also believed to be able to promote apolipoprotein B degradation in the liver through the stimulation of an autophagic process . It may also be possible that these fish oil acids can accelerate the clearance of very-low-density lipoprotein (VLDL) particles and chylomicron . The combination of all these actions results in fewer VLDL particles being assembled and secreted, which is of considerable importance as VLDL particles are the major endogenous source of triglycerides .

Moreover, new paradigms of how inflammation is contained and dissipated involve various newly discovered chemical mediators, resolvins, and protectins . Such agents are believed to be directly involved in blocking neutrophil migration, infiltration, recruitment, as well as blocking T-cell migration and promoting T-cell apoptosis . Additionally, such protectins can also reduce tumor necrosis factor and interferon secretion . Of particular importance, however, is the fact that protectins and resolvins are exclusively derived from omega-3-fatty acids and that EPA is the substrate of the resolvins family and DHA can be converted to both resolvins and protectins . It is believed that these effects of such fish oil acids underlie the actions that fish oil have demonstrated on eliciting stability for vulnerable inflammatory plaques .

Finally, fish oil acids have demonstrated certain direct electrophysiological effects on the myocardium . In animal studies, it was shown that the ventricular fibrillation threshold could be increased in both animals fed or infused with omega-3-fatty acids . Further studies subsequently revealed that such fatty acids could reduce both sodium currents and L-type calcium currents on a cellular and ion channel level . It is consequently hypothesized that during ischemia, a reduction in the sodium ion current protects hyperexcitable tissue, and a reduction in the calcium ion current could reduce arrhythmogenic depolarizing currents - and that perhaps the use of EPA and DHA fish oil acids could facilitate such activity . For the time being, however, omega-3-fatty acids in pharmaceutical supplement form have not been shown to elicit such protection against heart conditions .

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 stimulates 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 .

Dosage

Puspabio Kids dosage

Intravenous: Antidote in severe hypermagnesaemia, Severe hyperkalaemia:

• Adult: 10 ml of 10% calcium gluconate solution over 2 minutes, repeated every 10 minutes if needed.
• Child: Neonate and 1 mth-18 yr: 0.5 ml/kg of 10% calcium gluconate solution as a single dose. Max: 20 ml of 10% calcium gluconate solution.

Intravenous: Hypocalcaemic tetany, Severe acute hypocalcaemia:

• Adult: 2.25 mmol by slow IV inj over 10 minutes, followed by 58-77 ml of 10% calcium gluconate solution in 0.5-1 L of 5% dextrose solution as continuous IV infusion.
• Child: Neonate and 1 mth-18 yr: 0.5 ml/kg of 10% calcium gluconate solution as a single dose. Max: 20 ml of 10% calcium gluconate solution.

Side Effects

GI irritation; soft-tissue calcification, skin sloughing or necrosis after IM/SC inj. Hypercalcaemia characterised by anorexia, nausea, vomiting, constipation, abdominal pain, muscle weakness, mental disturbances, polydipsia, polyuria, nephrocalcinosis, renal calculi; chalky taste, hot flushes and peripheral vasodilation.

Toxicity

Infants : LDLo (Intramuscular ) : 10gm/kg ; Effects - Brain and coverings : meningeal changes Infants : TDLo ( Intramuscular ) : 143 mg/kg ; Effects - Dermatits Mouse: LD50 ( intravenous ) : 950mg/kg Mouse : LDLo (Oral ) : 10gm/kg

There have been some concerns that high doses of DHA and/or EPA (in the range of 900mg/day or EPA plus 600 mg/day of DHA or more for several weeks) could potentially reduce an individual's immune function due to the suppression of inflammatory responses . However, according to the European Food Safety Authority, long-term consumption of EPA and DHA supplements at combined doses of up to about 5 g/day appears to be safe .

Commonly reported side effects of omega-3 supplements are usually mild . These include unpleasant taste, bad breath, heartburn, nausea, gastrointestinal discomfort, diarrhea, headache, and odoriferous sweat .

The use of pharmacological or nutraceutical vitamin d and/or even excessive dietary intake of vitamin d is contraindicated in patients with hypercalcemia, malabsorption syndrome, abnormal sensitivity to the toxic effects of vitamin d, and hypervitaminosis D .

Hypersensitivity to vitamin d is one plausible etiologic factor in infants with idiopathic hypercalcemia - a case in which vitamin d use must be strictly restricted .

As vitamin d intake is available via fortified foods, dietary supplements, and clinical drug sources, serum concentrations and therapeutic dosages should be reviewed regularly and readjusted as soon as there is clinical improvement . Dosage levels are required to be individualized on an individual patient by patient basis as caution must be exercised to prevent the presence of too much vitamin d in the body and the various potentially serious toxic effects associated with such circumstances .

In particular, the range between therapeutic and toxic doses is quite narrow in vitamin d resistant rickets . When high therapeutic doses are used, progress should be followed with frequent blood calcium determinations .

When treating hypoparathyroidism, intravenous calcium, parathyroid hormone, and/or dihydrotachysterol may be required .

Maintenance of normal serum phosphorus levels by dietary phosphate restriction and/or administration of aluminum gels as intestinal phosphate binders in those patients with hyperphosphatemia as frequently seen in renal osteodystrophy is essential to prevent metastatic calcification .

Mineral oil interferes with the absorption of lipid-soluble vitamins, including vitamin d preparations .

The administration of thiazide diuretics to hypoparathyroid patients who are concurrently being treated with vitamin d can result in hypercalcemia .

At this time, no long term animal studies have been performed to evaluate vitamin potential for carcinogens, mutagenesis, or fertility .

As various animal reproduction studies have demonstrated fetal abnormalities in several species associated with hypervitaminosis D, the use of vitamin d in excess of the recommended dietary allowance during normal pregnancy should be avoided . The safety in excess of 400 USP units of vitamin d daily during pregnancy has not been established . The abnormalities observed are similar to the supravalvular aortic stenosis syndrome described in infants that is characterized by supravalvular aortic stenosis, elfin facies, and mental retardation .

In a nursing mother given large doses of vitamin D, 25-hydroxycholecalciferol appeared in the milk and caused hypercalcemia in her child. Caution is subsequently required when contemplating the use of vitamin d in a nursing woman, and the necessity of monitoring infants' serum calcium concentration if vitamin d is administered to a breastfeeding woman .

Adverse reactions associated with the use of vitamin d are primarily linked to having hypervitaminosis D occurring [FDA Lanel]. In particular, hypervitaminosis D is characterized by effects specific effects on specific organ systems. At the renal system, hypervitaminosis D can cause impairment of renal function with polyuria, nocturne, polydipsia, hypercalciuria, reversible asotemia, hypertension, nephrocalcinosis, generalized vascular calcification, or even irreversible renal insufficiency which may result in death . Elsewhere, hypervitaminosis D can also cause CNS mental retardation . At the level of soft tissues, it can widespread calcification of the soft tissues, including the heart, blood vessels, renal tubules, and lungs . In the skeletal system, bone demineralization (osteoporosis) in adults can occur while a decline in the average rate of linear growth and increased mineralization of bones, dwarfism, vague aches, stiffness, and weakness can occur in infants and children . Finally, hypervitaminosis D can also lead to nausea, anorexia, and constipation at the gastrointestinal level as well as mild acidosis, anemia, or weight loss via metabolic processes .

The LD(50) in animals is unknown .

Precaution

Impaired renal function; cardiac disease; hypercalcaemia-associated diseases, e.g. sarcoidosis; other malignancies. Pregnancy.

Interaction

Co-administration of high calcium doses with thiazide diuretics may result in milk-alkali syndrome and hypercalcaemia. May potentiate digoxin toxicity. Decreases effects of calcium-channel blockers. Enhanced absorption with calcitriol (a vitamin D metabolite).

Volume of Distribution

Not available

The volume of distribution of EPA is documented as being approximately 82 L .

Elimination Route

Approximately one-fifth to one-third of orally administered calcium is absorbed in the small intestine, depending on presence of vitamin D metabolites, pH in lumen, and on dietary factors, such as calcium binding to fiber or phytates. Calcium absorption is increased when a calcium deficiency is present or when a patient is on a low-calcium diet. In patients with achlorhydria or hypochlorhydria, calcium absorption, especially with the carbonate salt, may be reduced.

The absorption process of fish oil EPA and DHA acids have been documented as being very efficient, with an absorption rate of about 95%, which is similar to that of other ingested fats .

Vitamin D3 and D2 are readily absorbed from the small intestine (proximal or distal) .

Half Life

The half-life of EPA is recorded to be about 37 hours while that of DHA is documented to be about 46 hours .

Although certain studies suggest the half-life of 1,25-hydroxyvitamin D3 may be approximately 15 hours, the half-life of 25-hydroxyvitamin D3 appears to have a half-life of about 15 days . Intriguingly however, the half-lives of any particular administration of vitamin d can vary and in general the half-lives of vitamin D2 metabolites have been demonstrated to be shorter overall than vitamin D3 half-lives with this being affected by vitamin d binding protein concentrations and genotype in particular individuals .

Clearance

The clearance of EPA is recorded to be about 548 ml/hr while that of DHA is documented to be about 518 ml/hr hours .

Some studies propose an estimated clearance rate for 1,25-dihydroxyvitamin D as 31 +/- 4 ml/min in healthy adults .

Elimination Route

Renal (20%) - The amount excreted in the urine varies with degree of calcium absorption and whether there is excessive bone loss or failure of renal conservation. Fecal (80%) - Consists mainly of nonabsorbed calcium, with only a small amount of endogenous fecal calcium excreted.

Based on what is known about the elimination of EPA and DHA, it is understood that such fatty acids do not undergo renal excretion .

The primary excretion route of vitamin D is via the bile into the feces .

Pregnancy & Breastfeeding use

Pregnancy Category C. Either studies in animals have revealed adverse effects on the fetus (teratogenic or embryocidal or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the fetus.

Contraindication

Patients with calcium renal calculi or history of renal calculi. Conditions associated with hypercalcaemia and hypercalciuria.

Innovators Monograph

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