Pharm drug MOA 3 OM3FA - Omega 3 Fatty Acids mechanism of action PDF

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Omega 3 Fatty Acids mechanism of action...

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Rebecca Gotthelf 4/20/2019 Omega-3 Fatty Acid MOA Omega-3 fatty acids are long-chain polyunsaturated fats. They have several uses throughout the body, including anti-inflammatory effects, decreased platelet aggregation, and decreased plasma triglyceride levels. They are known to decrease risk of chronic heart disease (CHD), and can treat patients with hypertriglyceridemia. Often taken as a pill, Omega-3 fatty acids are made up of three different essential fatty acids, eicosapetaenoic acid (EPA), docosahexaenoic acid (DHA), and lastly, alpha-linolenic acid (ALA). Typically, Omega-3 fatty acids can be obtained from either a supplement or through diet. ALA is found in plants such as leafy greens or vegetable oils, while DHA and EPA is often found in seafood (fish). EPA and DHA are absorbed from the gastrointestinal tract, and are transported to the liver as triglycerides in lipoprotein particles (such as VLDL and HDL) and as plasma phospholipids. Increased levels of EPA or DHA has been show to decrease levels of PGE2 and 4 series-LT. EPA compete with constitutive levels of arachidonic acid in cell membranes for the same desaturation enzymes and produce 3-series prostaglandins and thromboxanes, and 5-series leukotrienes which have low pro-inflammatory potential. Essentially, meaning that EPA and DHA competitively and reversibly inhibit the same desaturation enzymes as arachidonic acid, which further promotes anti-inflammatory effects. EPA and DHA also produce resolvins (which are part of a biochemical system which allows inflamed tissues to return to homeostasis once the need for that inflammatory response is over) and lipid signaling molecules such as protectins (which also help to resolve the inflammatory response) through cyclooxygenase and lipoxygenase pathways. Omega-3 [polyunsaturated] fatty acids and their metabolites are natural ligands for peroxisome proliferator-activated receptor (PPAR) gamma that regulates inflammatory gene expression. A large role of EPA and DHA in terms of reducing plasma triglyceride concentration is through the inhibition of acyl-CoA: 1,2 diacylglycerol acyltransferase. Acyl CoA: 1,2 diacylglycerol acyltransferase is a membrane bound enzyme which catalyzes the biosynthesis of triacylglycerols. Through this inhibition, there is a decreased synthesis of triglycerides, which leads to a decreased plasma concentration of triglycerides. EPA and DHA also increase mitochondrial and peroxisomal-beta-oxidation in the liver, decrease lipogenesis (the formation of triglycerides from acetyl-CoA) in the liver, and increase plasma lipoprotein lipase activity. Lipoprotein lipase catalyzes the hydrolysis of the triacylglycerol component of circulating chylomicrons and VLDL. With decreased chylomicrons, VLDL and triglycerides, there is ultimately less plasma LDL circulating. Increasing peroxisomal-beta oxidation of very long chain fatty acids allows the fatty acids to be broken down and release energy for the body to utilize. Omega-3 fatty acids have a relatively low potency. The daily fish oil (OM3FAs) dosage for adults should be from 2000mg to 3000mg of EPA and DHA combined. Even while taking that much, it still takes approximately 8-12 weeks until the desired therapeutic effects start to kick in. The efficacy is also something that should be examined. Fish oils, which are often taken interchangeably with omega-3 fatty acids, typically only contain 30% of EPA and DHA combined, which means if a 1000mg capsule is taken, only 300mg of that is EPA and DHA. The absorption of omega-3 fatty acids started with the hydrolysis of the dietary lipids in the intestinal lumen. The products of hydrolysis, monoglycerides and free fatty acids are then incorporated into bile salt-containing micelles and absorbed into enterocytes though passive diffusion. The absorption rate is around 95%. All three of the omega-3 fatty acid components, ALA, DHA, and EPA are metabolized and oxidized in the liver. Omega-3 fatty acids. (n.d.). Retrieved from https://www.drugbank.ca/drugs/DB11133 Omega-3 Fatty Acids: An Essential Contribution. (2018, June 04). Retrieved from https://www.hsph.harvard.edu/nutritionsource/what-should-you-eat/fats-and-cholesterol/types-of-fat/omega-3-fats/ Visioli, F., Giordano, E., Nicod, N. M., & Dávalos, A. (2012, February 29). Molecular targets of omega 3 and conjugated linoleic Fatty acids - "micromanaging" cellular response. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3289952/ (n.d.). Retrieved from https://www.uptodate.com/contents/fish-oil-and-marine-omega-3-fatty-acids?search=polyunsaturated fatty acids&source=search_result&selectedTitle=4~112&usage_type=default&display_rank=4...