Metformin (Glucophage) Reactions

metformin (Glucophage) ReactionsMetformin (Glucophage) is available in the Pakistan since 1998. It falls in the same drug class as phenformin. Metformin is considered a first line agent and is significantly exercisingful in people with known insulin resistanceGLUCOPHAGE (metformin hydrochloride tablets) and GLUCOPHAGE XR (metformin hydrochloride extended-release tablets) are oral antihyperglycemic drugs use in the management of type 2 diabetes. Metformin hydrochloride (N,N-dimethylimidodicarbonimidic diamide hydrochloride) is not chemically or pharmacologically related to any other classes of oral antihyperglycemic agents. The structural decree is as shownGlucophage (metformin hydrochloride tablets) Structural Formula IllustrationMetformin hydrochloride is a white to off-white crystalline compound with a molecular formula of C4H11N5 HCl and a molecular weight of 165.63.Metformin improves hyperglycemia primarily by dint of its suppression of hepatic glucose production, especially h epatic gluconeogenesis1. The average person with type 2 diabetes has third times the normal rate of gluconeogenesis metformin treatment reduces this by over one third.2 Metformin activates AMP-activated protein kinase (AMPK), a liver enzyme that plays an important role in insulin signaling, safe and sound body energy balance, and the metabolism of glucose and fats3 activation of AMPK is required for metformins inhibitory effect on the production of glucose by liver cells.4 Research published in 2008 hike up elucidated metformins mechanism of action, showing that activation of AMPK is required for an increase in the expression of SHP (Small heterodimer partner), which in turn inhibits the expression of the hepatic gluconeogenic genes PEPCK and Glc-6-Pase.5 Metformin is frequently used in research along with AICAR as an AMPK agonist. The mechanism by which biguanides increase the exertion of AMPK remains uncertain however, research suggests that metformin increases the amount of c ytosolic AMP (as opposed to a change in total AMP or total AMP/ATP).6In addition to suppressing hepatic glucose production, metformin increases insulin sensitivity, enhances peripheral glucose uptake, decreases fatty acid oxidation, and decreases preoccupancy of glucose from the gastrointestinal tract.8 Increased peripheral utilization of glucose may be due to improved insulin binding to insulin receptors.9 AMPK probably also plays a role, as metformin judgeship increases AMPK activity in skeletal muscle.10 AMPK is known to cause GLUT4 translocation, resulting in insulin-independent glucose uptake. Some metabolic actions of metformin do appear to occur by AMPK-independent mechanisms a new-fashioned study found that the metabolic actions of metformin in the heart muscle can occur independent of changes in AMPK activity and may be negotiate by p38 MAPK- and PKC-dependent mechanisms.11Metformin causes a few gastrointestinal side effects including nausea, metallic taste, diarrhea and abdominal discomfort7 . These can be avoided if the dose is increased slowly, and taking the drug with meals. A small amount of weight loss, possibly due to drop in net caloric intake due to appetite repression and/or a reduction in hyperinsulinemia is suggested. Falling in the same drug class as phenformin, the reported incidence of lactic acidosis is surprisingly low, 0.03 per 1000.In a US double-blind clinical study of GLUCOPHAGE in patients with type 2 diabetes, a total of 141 patients received GLUCOPHAGE therapy (up to 2550 mg per day) and 145 patients received placebo. roughly Common Adverse Reactions (5.0 Percent) in a Placebo-Controlled Clinical Study of GLUCOPHAGE MonotherapyThe occurrence can further be avoided if contraindications are followed. It is contraindicated in people with a high risk of lactic acidosis renal serum creatinine levels over 150 mol/l14or hepatic impairment, respiratory insufficiency, severe infection and alcohol abuse. all pharmacological therapy that alters either of the factors mentioned before is also considered. It should also be used cautiously in elderly especially those above 80 years of age. It is recommended to observe renal function upon initiation and at least once a year thereafter.It should be withheld immediately before a person has a mathematical process with a radiocontrast dye, as the dye increases the risk of renal failure and therefore lactic acidosis 15 16. It should also be discontinued before and surgery and can be started immediately after if the renal function is normal and the patient is stable. It is also recommended to monitor hematological parameters as it alters vitamin B12 absorption 12 13 and therefore cause anemia (7% in clinical trials). The mechanism of action is unknown but can be reversed by discontinuation of the drug.Daily dosage should be 500 mg orally twice daily with meals. The dose can be increased every 2 weeks to 2000 mg daily.ReferencesKirpichnikov D, McFarlane SI, Sowers JR (20 02). Metformin an update. Ann Intern Med 137 (1) 25-33. PMID 12093242.Hundal R, Krssak M, Dufour S, Laurent D, Lebon V, Chandramouli V, Inzucchi S, Schumann W, Petersen K, Landau B, Shulman G (2000). Mechanism by which metformin reduces glucose production in type 2 diabetes (PDF). Diabetes 49 (12) 2063-9. doi10.2337/diabetes.49.12.2063. PMID 11118008.Towler MC, Hardie DG (2007). AMP-activated protein kinase in metabolic control and insulin signaling. Circ Res 100 (3) 328-41. doi10.1161/01.RES.0000256090.42690.05. PMID 17307971. chow chow G, Myers R, Li Y, Chen Y, Shen X, Fenyk-Melody J, Wu M, Ventre J, Doebber T, Fujii N, Musi N, Hirshman M, Goodyear L, Moller D (2001). Role of AMP-activated protein kinase in mechanism of metformin action. J Clin Invest 108 (8) 1167-74. doi10.1172/JCI13505. PMID 11602624.Kim YD, Park KG, Lee YS, et al. (2008). Metformin inhibits hepatic gluconeogenesis through AMP-activated protein kinase-dependent regulation of the orphan nuclear receptor SHP. Diab etes 57 (2) 306-14. doi10.2337/db07-0381. PMID 17909097.Zhang L, He H, Balschi JA (2007). Metformin and phenformin activate AMP-activated protein kinase in the heart by increasing cytosolic AMP concentration. Am J Physiol Heart Circ Physiol 293 (1) H457-66. doi10.1152/ajpheart.00002.2007. PMID 17369473.Bolen S, Feldman L, Vassy J, et al (2007). Systematic review comparative effectiveness and safety of oral medications for type 2 diabetes mellitus. Ann Intern Med 147 (6) 386-99. PMID 17638715.Royal pharmaceutic Society of Great Britain and the British Medical Association. Chapter 6Endocrine system6.1.2.2 Biguanides, British National Formulary, 54.Bailey CJ, Turner RC (1996). Metformin. N Engl J Med 334 (9) 574-9. doi10.1056/NEJM199602293340906. PMID 8569826.Musi N, Hirshman MF, Nygren J, et al. (2002). Metformin increases AMP-activated protein kinase activity in skeletal muscle of subjects with type 2 diabetes. Diabetes 51 (7) 2074-81. PMID 12086935.Saeedi R, Parsons HL, Wambolt RB, et al. (2008). Metabolic actions of metformin in the heart can occur by AMPK-independent mechanisms. Am J Physiol Heart Circ Physiol 294 (6) H2497-506. doi10.1152/ajpheart.00873.2007. PMID 18375721Andrs E, Noel E, Goichot B (2002). Metformin-associated vitamin B12 deficiency. Arch Intern Med 162 (19) 2251-2. doi10.1001/archinte.162.19.2251-a. PMID 12390080.Gilligan M (2002). Metformin and vitamin B12 deficiency. Arch Intern Med 162 (4) 484-5. doi10.1001/archinte.162.4.484. PMID 11863489Jones G, Macklin J, Alexander W (2003). Contraindications to the use of metformin. BMJ 326 (7379) 4-5. doi10.1136/bmj.326.7379.4. PMID 12511434Weir J (March 19, 1999). Guidelines with Regard to Metformin-Induced Lactic Acidosis and X-ray Contrast Medium Agents. Royal College of Radiologists. Retrieved on 2007-10-26 through the Internet Archive.a b Thomsen HS, Morcos SK (2003). Contrast media and the kidney European Society of Urogenital Radiology (ESUR) guidelines. Br J Radiol 76 (908) 513-8. doi10.12 59/bjr/26964464. 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