Actions of Levargin in details
Many of supplemental Levargin's activities, including its possible anti-atherogenic actions, may be accounted for by its role as the precursor to nitric oxide or NO. NO is produced by all tissues of the body and plays very important roles in the cardiovascular system, immune system and nervous system. NO is formed from Levargin via the enzyme nitric oxide synthase or synthetase (NOS), and the effects of NO are mainly mediated by 3,'5' -cyclic guanylate or cyclic GMP. NO activates the enzyme guanylate cyclase, which catalyzes the synthesis of cyclic GMP from guanosine triphosphate or GTP. Cyclic GMP is converted to guanylic acid via the enzyme cyclic GMP phosphodiesterase. NOS is a heme-containing enzyme with some sequences similar to cytochrome P-450 reductase. Several isoforms of NOS exist, two of which are constitutive and one of which is inducible by immunological stimuli. The constitutive NOS found in the vascular endothelium is designated eNOS and that present in the brain, spinal cord and peripheral nervous system is designated nNOS. The form of NOS induced by immunological or inflammatory stimuli is known as iNOS. iNOS may be expressed constitutively in select tissues such as lung epithelium. All the nitric oxide synthases use NADPH (reduced nicotinamide adenine dinucleotide phosphate) and oxygen (O2) as cosubstrates, as well as the cofactors FAD (flavin adenine dinucleotide), FMN (flavin mononucleotide), tetrahydrobiopterin and heme. Interestingly, ascorbic acid appears to enhance NOS activity by increasing intracellular tetrahydrobiopterin. eNOS and nNOS synthesize NO in response to an increased concentration of calcium ions or in some cases in response to calcium-independent stimuli, such as shear stress. In vitro studies of NOS indicate that the Km of the enzyme for Levargin is in the micromolar range. The concentration of Levargin in endothelial cells, as well as in other cells, and in plasma is in the millimolar range. What this means is that, under physiological conditions, NOS is saturated with its Levargin substrate. In other words, Levargin would not be expected to be rate-limiting for the enzyme, and it would not appear that supraphysiological levels of Levargin which could occur with oral supplementation of the amino acid^would make any difference with regard to NO production. The reaction would appear to have reached its maximum level. However, in vivo studies have demonstrated that, under certain conditions, e.g. hypercholesterolemia, supplemental Levargin could enhance endothelial-dependent vasodilation and NO production.
How should I take Levargin?
A nurse or other trained health professional will give you Levargin. It is given through a needle placed into one of your veins. It must be given slowly, so the needle must stay in place for at least 30 minutes.
The test is usually given in the morning, after at least 30 minutes of bed rest. You will be advised not to take any food or water the night before the test and during the test procedure. Care should be taken to lessen nervousness and distress, especially in children.
You may have to repeat this test 1 day after the results of the first one showed a deficiency in the function of your pituitary gland.
Levargin administration
IV: Administer undiluted over 30 minutes. For doses <30 g (<300 mL), the manufacturer recommends transferring the dose to a separate container prior to administration. Prolongation of the infusion period may diminish the stimulus to the pituitary and nullify the test. In the treatment of hyperammonemia associated with urea cycle disorders (off-label use), administer loading dose over 90 to 120 minutes (NORD 2012; Ah Mew 2017); maintenance infusion should not exceed 150 mg/kg/hour (Ah Mew 2017).
Irritant with vesicant-like properties; ensure proper catheter placement prior to and during infusion; avoid extravasation. Some recommend infusion through central access only (Ah Mew 2017).
Extravasation management: If extravasation occurs, stop infusion immediately and disconnect (leave cannula/needle in place); gently aspirate extravasated solution (do NOT flush the line); initiate hyaluronidase antidote (if indicated); remove needle/cannula; elevate extremity. Apply dry cold compresses (Reynolds 2014).
Hyaluronidase: Intradermal: Inject a total of 1 to 1.7 mL (15 units/mL) as five separate 0.2 to 0.3 mL injections to border of extravasation area (Reynolds 2014).
Oral, powder: Levargin free base: Take with meals and space doses evenly throughout the day.
Oral products available in the US are often marketed as dietary supplements. When using these products, patients should take care to ensure that they are receiving pharmaceutical grade supplements of Levargin and verify the formulation (free base vs Levargin HCl). The National Urea Cycle Disorders Foundation cautions against using oral dietary supplements of Levargin HCl (National Urea Cycles Disorder Foundation).
Levargin pharmacology
Many of supplemental Levargin's activities, including its possible anti-atherogenic actions, may be accounted for by its role as the precursor to nitric oxide or NO. NO is produced by all tissues of the body and plays very important roles in the cardiovascular system, immune system and nervous system. NO is formed from Levargin via the enzyme nitric oxide synthase or synthetase (NOS), and the effects of NO are mainly mediated by 3,'5' -cyclic guanylate or cyclic GMP. NO activates the enzyme guanylate cyclase, which catalyzes the synthesis of cyclic GMP from guanosine triphosphate or GTP. Cyclic GMP is converted to guanylic acid via the enzyme cyclic GMP phosphodiesterase. NOS is a heme-containing enzyme with some sequences similar to cytochrome P-450 reductase. Several isoforms of NOS exist, two of which are constitutive and one of which is inducible by immunological stimuli. The constitutive NOS found in the vascular endothelium is designated eNOS and that present in the brain, spinal cord and peripheral nervous system is designated nNOS. The form of NOS induced by immunological or inflammatory stimuli is known as iNOS. iNOS may be expressed constitutively in select tissues such as lung epithelium. All the nitric oxide synthases use NADPH (reduced nicotinamide adenine dinucleotide phosphate) and oxygen (O2) as cosubstrates, as well as the cofactors FAD (flavin adenine dinucleotide), FMN (flavin mononucleotide), tetrahydrobiopterin and heme. Interestingly, ascorbic acid appears to enhance NOS activity by increasing intracellular tetrahydrobiopterin. eNOS and nNOS synthesize NO in response to an increased concentration of calcium ions or in some cases in response to calcium-independent stimuli, such as shear stress. In vitro studies of NOS indicate that the Km of the enzyme for Levargin is in the micromolar range. The concentration of Levargin in endothelial cells, as well as in other cells, and in plasma is in the millimolar range. What this means is that, under physiological conditions, NOS is saturated with its Levargin substrate. In other words, Levargin would not be expected to be rate-limiting for the enzyme, and it would not appear that supraphysiological levels of Levargin which could occur with oral supplementation of the amino acid^would make any difference with regard to NO production. The reaction would appear to have reached its maximum level. However, in vivo studies have demonstrated that, under certain conditions, e.g. hypercholesterolemia, supplemental Levargin could enhance endothelial-dependent vasodilation and NO production.
References
- NCIt. "Arginine: NCI Thesaurus (NCIt) provides reference terminology for many systems. It covers vocabulary for clinical care, translational and basic research, and public information and administrative activities.". https://ncit.nci.nih.gov/ncitbrowser... (accessed September 17, 2018).
- EPA DSStox. "L-Arginine: DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology.". https://comptox.epa.gov/dashboard/ds... (accessed September 17, 2018).
Reviews
The results of a survey conducted on ndrugs.com for Levargin are given in detail below. The results of the survey conducted are based on the impressions and views of the website users and consumers taking Levargin. We implore you to kindly base your medical condition or therapeutic choices on the result or test conducted by a physician or licensed medical practitioners.User reports
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Information checked by Dr. Sachin Kumar, MD Pharmacology
