VITALIPID N INFANT INJECTION

Indication

For use in the management of hypocalcemia and its clinical manifestations in patients with hypoparathyroidism, as well as for the treatment of familial hypophosphatemia (vitamin D resistant rickets). This drug has also been used in the treatment of nutritional rickets or osteomalacia, vitamin D dependent rickets, rickets or osteomalacia secondary to long-term high dose anticonvulsant therapy, early renal osteodystrophy, osteoporosis (in conjunction with calcium), and hypophosphatemia associated with Fanconi syndrome (with treatment of acidosis).

Mechanism of Action

Activated ergocalciferol increases serum calcium and phosphate concentrations, primarily by increasing intestinal absorption of calcium and phosphate through binding to a specific receptor in the mucosal cytoplasm of the intestine. Subsequently, calcium is absorbed through formation of a calcium-binding protein. 25-hydroxyergocalciferol is the intermediary metabolite of ergocalciferol. Although this metabolite exhibits 2–5 times more activity than unactivated ergocalciferol in curing rickets and inducing calcium absorption and mobilization (from bone) in animals, this increased activity is still insufficient to affect these functions at physiologic concentrations. Activated ergocalciferol stimulate resorption of bone and are required for normal mineralization of bone. Physiological doses of ergocalciferol also promotes calcium reabsorption by the kidneys, but the significance of this effect is not known.

Pharmacokinetics

Absorption

Readily absorbed from small intestine (proximal or distal), requires presence of bile salts.

Distribution

Metabolism

Within the liver, ergocalciferol is hydroxylated to ercalcidiol (25-hydroxyergocalciferol) by the enzyme 25-hydroxylase. Within the kidney, ercalcidiol serves as a substrate for 1-alpha-hydroxylase, yielding ercalcitriol (1,25-dihydroxyergocalciferol), the biologically active form of vitamin D2.

Elimination

Toxicity

LD₅₀ = 23.7 mg/kg (Orally in mice); LD₅₀ = 10 mg/kg (Orally in rats ); Nausea, vomiting and diarrhea, weight loss, irritability, weakness, fatigue, lassitude, and headache.

Active Ingredient/Synonyms

(3β,5Z,7E,22E)-9,10-secoergosta-5,7,10(19),22-tetraen-3-ol | (5Z,7E,22E)-(3S)-9,10-seco-5,7,10(19),22-ergostatetraen-3-ol | (5Z,7E,22E)-(3S)-9,10-secoergosta-5,7,10(19),22-tetraen-3-ol | Activated ergosterol | Ercalciol | Ergocalciférol | Ergocalciferol | Ergocalciferolum | Oleovitamin D2 | Viosterol | Vitamin D2 | Vitamina D2 | Ergocalciferol |

Indication

Vitamin E, known for its antioxidant activities, is protective against cardiovascular disease and some forms of cancer and has also demonstrated immune-enhancing effects. It may be of limited benefit in some with asthma and rheumatoid arthritis. It may be helpful in some neurological diseases including Alzheimer's, some eye disorders including cataracts, and diabetes and premenstrual syndrome. It may also help protect skin from ultraviolet irradiation although claims that it reverses skin aging, enhances male fertility and exercise performance are poorly supported. It may help relieve some muscle cramps.

Mechanism of Action

Although all forms of Vitamin E exhibit antioxidant activity, it is known that the antioxidant activity of vitamin E is not sufficient to explain the vitamin's biological activity.
Vitamin E's anti-atherogenic activity involves the inhibition of the oxidation of LDL and the accumulation of oxLDL in the arterial wall. It also appears to reduce oxLDL-induced apoptosis in human endothelial cells. Oxidation of LDL is a key early step in atherogenesis as it triggers a number of events which lead to the formation of atherosclerotic plaque. In addition, vitamin E inhibits protein kinase C (PKC) activity. PKC plays a role in smooth muscle cell proliferation, and, thus, the inhibition of PKC results in inhibition of smooth muscle cell proliferation, which is involved in atherogenesis.
Vitamin E's antithrombotic and anticoagulant activities involves the downregulation of the expression of intracellular cell adhesion molecule(ICAM)-1 and vascular cell adhesion molecule(VCAM)-1 which lowers the adhesion of blood components to the endothelium. In addition, vitamin E upregulates the expression of cytosolic phospholipase A2 and cyclooxygenase (COX)-1 which in turn enhances the release of prostacyclin. Prostacyclin is a vasodilating factor and inhibitor of platelet aggregation and platelet release. It is also known that platelet aggregation is mediated by a mechanism involving the binding of fibrinogen to the glycoprotein IIb/IIIa (GPIIb/IIIa) complex of platelets. GPIIb/IIIa is the major membrane receptor protein that is key to the role of the platelet aggregation response. GPIIb is the alpha-subunit of this platelet membrane protein. Alpha-tocopherol downregulates GPIIb promoter activity which results in reduction of GPIIb protein expression and decreased platelet aggregation. Vitamin E has also been found in culture to decrease plasma production of thrombin, a protein which binds to platelets and induces aggregation. A metabolite of vitamin E called vitamin E quinone or alpha-tocopheryl quinone (TQ) is a potent anticoagulant. This metabolite inhibits vitamin K-dependent carboxylase, which is a major enzyme in the coagulation cascade.
The neuroprotective effects of vitamin E are explained by its antioxidant effects. Many disorders of the nervous system are caused by oxidative stress. Vitamin E protects against this stress, thereby protecting the nervouse system.
The immunomodulatory effects of Vitamin E have been demonstrated in vitro, where alpha-tocopherol increases mitogenic response of T lymphocytes from aged mice. The mechanism of this response by vitamin E is not well understood, however it has been suggested that vitamin E itself may have mitogenic activity independent of its antioxidant activity.
Lastly, the mechanism of action of vitamin E's antiviral effects (primarily against HIV-1) involves its antioxidant activity. Vitamin E reduces oxidative stress, which is thought to contribute to HIV-1 pathogenesis, as well as to the pathogenesis of other viral infections. Vitamin E also affects membrane integrity and fluidity and, since HIV-1 is a membraned virus, altering membrane fluidity of HIV-1 may interfere with its ability to bind to cell-receptor sites, thus decreasing its infectivity.

Pharmacokinetics

Absorption

50 to 80% absorbed from gastrointestinal tract.

Distribution

Metabolism

Hepatic.

Elimination

Active Ingredient/Synonyms

(+)-α-tocopherol | (2R,4'R,8'R)-α-tocopherol | (2R)-2,5,7,8-TETRAMETHYL-2-[(4R,8R)-4,8,12-TRIMETHYLTRIDECYL]CHROMAN-6-OL | (R,R,R)-α-tocopherol | 5,7,8-trimethyltocol | alpha-tocopherol | d-α-tocopherol | Vitamin E |

Indication

For the treatment of haemorrhagic conditions in infants, antidote for coumarin anticoagulants in hypoprothrombinaemia.

Mechanism of Action

Vitamin K is an essential cofactor for the gamma-carboxylase enzymes which catalyze the posttranslational gamma-carboxylation of glutamic acid residues in inactive hepatic precursors of coagulation factors II (prothrombin), VII, IX and X. Gamma-carboxylation converts these inactive precursors into active coagulation factors which are secreted by hepatocytes into the blood. Supplementing with Phylloquinone results in a relief of vitamin K deficiency symptoms which include easy bruisability, epistaxis, gastrointestinal bleeding, menorrhagia and hematuria.

Pharmacokinetics

Absorption

Oral phylloquinone is adequately absorbed from the gastrointestinal tract only if bile salts are present. After absorption, phylloquinone is initially concentrated in the liver, but the concentration declines rapidly. Very little vitamin K accumulates in tissues.

Distribution

Metabolism

Elimination

Toxicity

The intravenous LD₅₀ of phylloquinone in the mouse is 41.5 and 52 mL/kg for the 0.2% and 1% concentrations, respectively.

Active Ingredient/Synonyms

2-Methyl-3-(3,7,11,15-tetramethyl-2-hexadecenyl)-1,4-naphthalenedione | 2-Methyl-3-[(2e)-3,7,11,15-tetramethyl-2-hexadecenyl]naphthoquinone | 2-Methyl-3-phytyl-1,4-naphthochinon | 2-Methyl-3-phytyl-1,4-naphthoquinone | 3-Phytylmenadione | alpha-Phylloquinone | Fitomenadiona | Phyllochinon | Phyllochinonum | Phylloquinone | Phythyl-menadion | Phytomenadione | Phytomenadionum | Phytonadionum | Phytylmenadione | trans-Phylloquinone | Vitamin k | Vitamin K1 | α-phylloquinone | Phylloquinone |