Omegaflex Peri/Omegaflex Special Mechanism of Action

Pharmacotherapeutic group: Solutions for parenteral nutrition, combinations. ATC code: B05BA10.
Pharmacology: Pharmacodynamics: Mechanism of action: The purpose of parenteral nutrition is to supply all necessary nutrients and energy for the growth and/or regeneration of tissue as well as for the maintenance of all body functions.
Amino acids are of particular importance, since some of them are essential components for protein synthesis. The simultaneous administration of energy sources (carbohydrates/lipids) is necessary to reserve amino acids for tissue regeneration and anabolism, and prevent their utilisation as energy source.
Glucose is ubiquitously metabolised within the organism. Some tissues and organs, such as CNS, bone marrow, erythrocytes, tubular epithelium, cover their energy requirement exclusively from glucose. In addition, glucose acts as a structural building block for various cell substances.
On account of their high energy density, lipids are an efficient form of energy supply. Long-chain triglycerides provide the organism with essential fatty acids for the synthesis of cell components. For this purpose, the fat emulsion contains medium-chain and long-chain triglycerides (deriving from soya-bean oil and fish oil).
The long-chain triglyceride fraction contains omega-6 and omega-3 triglycerides for supply of polyunsaturated fatty acids. They are primarily intended for the prevention and treatment of essential fatty acid deficiency, but also as a source of energy. OMEGAFLEX Peri Emulsion for Infusion/OMEGAFLEX Special Emulsion for Infusion contains essential omega-6 fatty acids, mainly in the form of linoleic acid, and omega-3 fatty acids in the form of alpha-linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid. The ratio of omega-6 to omega-3 fatty acids in OMEGAFLEX Peri Emulsion for Infusion/OMEGAFLEX Special Emulsion for Infusion is approximately 2.5:1.
Medium-chain triglycerides are more rapidly hydrolysed, eliminated from the circulation and completely oxidised than long-chain triglycerides. They are a favoured energy substrate, particularly when there is disturbance of the degradation and/or utilisation of long-chain triglycerides, e.g. when there is a lipoprotein lipase deficiency and/or a deficiency in lipoprotein lipase cofactors.
Pharmacokinetics: Absorption: OMEGAFLEX Peri Emulsion for Infusion/OMEGAFLEX Special Emulsion for Infusion is infused intravenously. Hence, all substrates are available for metabolism immediately.
Distribution: The dose, rate of infusion, metabolic situation and individual factors of the patient (level of fasting) are of decisive importance for the maximum triglyceride concentrations reached. When used according to the instructions with due regard to the dosage guidelines, the triglyceride concentrations do not, in general, exceed 4.6 mmol/L (400 mg/dL).
Medium-chain fatty acids have a low affinity to albumin. In animal experiments administering pure medium-chain triglyceride emulsions, it has been shown that medium-chain fatty acids can cross the blood-brain barrier, if overdosed. No adverse effects were observed with an emulsion providing a mixture of medium-chain triglycerides and long-chain triglycerides, as long-chain triglycerides have an inhibiting effect on medium-chain triglyceride hydrolysis. Therefore, toxic effects on the brain can be excluded after the administration of OMEGAFLEX Peri Emulsion for Infusion/OMEGAFLEX Special Emulsion for Infusion.
Amino acids are incorporated in a variety of proteins in different organs of the body. In addition, each amino acid is maintained as free amino acid in the blood and inside cells.
As glucose is water-soluble, it is distributed with the blood over the whole body. At first, the glucose solution is distributed in the intravascular space and then it is taken up into the intracellular space.
No data are available concerning transport of the components through the placental barrier.
Biotransformation: Amino acids that do not enter protein synthesis are metabolised as follows. The amino group is separated from the carbon skeleton by transamination. The carbon chain is either oxidised directly to CO₂ or utilised as substrate for gluconeogenesis in the liver. The amino group is also metabolised in the liver to urea.
Glucose is metabolised to CO₂ and H₂O via the known metabolic routes. Some glucose is utilised for lipid synthesis.
After infusion, triglycerides are hydrolysed to glycerol and fatty acids. Both are incorporated in physiological pathways for energy production, synthesis of biological active molecules, gluconeogenesis and resynthesis of lipids.
In detail, long-chain omega-3 polyunsaturated fatty acids replace arachidonic acid as an eicosanoid substrate in cell membranes and decrease the generation of inflammatory eicosanoids and cytokines in the body. This may be of benefit in patients at risk of developing a hyperinflammatory state and sepsis.
Elimination: Only minor amounts of amino acids are excreted unchanged in urine.
Excess glucose is excreted in urine only if the renal threshold of glucose is reached.
Both the triglycerides of soya-bean oil and medium-chain triglycerides are completely metabolised to CO₂ and H₂O. Small amounts of lipids are lost only during sloughing of cells from skin and other epithelial membranes. Renal excretion virtually does not occur.
Toxicology: Preclinical safety data: Toxic effects of mixtures of nutrients given as substitution therapy at the recommended dosage are not to be expected.
Reproductive toxicity: Phytoestrogens such as β-sitosterol can be found in various vegetable oils, especially in soya-bean oil. Impairment of fertility was observed in rats and rabbits after subcutaneous and intravaginal administration of β-sitosterol. After administration of pure β-sitosterol, a decrease of the testicular weight and a reduction of the sperm concentration in male rats and a lowered pregnancy rate in female rabbits were recorded. However, according to the current state of knowledge, the observed effects in animals do not seem to have relevance for clinical use.
Omegaflex Peri: Preclinical studies, including safety pharmacology, reproductive and developmental toxicity studies, with a lipid emulsion containing twice the amount of omega-3 acid triglycerides and a correspondingly smaller amount of omega-6 triglycerides revealed no effects other than those expected following administration of high doses of lipids.
Omegaflex Special: Preclinical studies have not been performed with OMEGAFLEX Special Emulsion for Infusion.