Metformin

Metformin. Metformin [657-24-9] (1,1-dimethylbiguanide), mol wt 129.17, forms crystals from propanol, mp 218—220°C, and is soluble in water and 95% ethanol, but practically insoluble in ether and chloroform. Metformin, an investigational dmg in the United States, does not increase basal or meal-stimulated insulin secretion. It lowers blood glucose levels in hyperglycemic patients with Type II diabetes but has no effect on blood glucose levels in normal subjects. It does not cause hypoglycemia. Successful metformin therapy usually is associated with no or some weight loss. 

Biguanide Metformin Improve insulin action Oral... 

Metformin restrains hepatic glucose production principally by suppression of gluconeogenesis. The mechanisms involve potentiation of insulin action and decreased hepatic extraction of certain gluconeogenic substrates such as lactate. In addition, metformin reduces the rate of hepatic glycogenolysis and decreases the activity of hepatic glucose-6-phosphatase. Insulin-stimulated glucose uptake and glycogenesis by skeletal muscle is increased by metformin mainly by increased... 

Antidiabetic Drugs other than Insulin. Figure 3 The antihyperglycaemic effect of metformin involves enhanced insulin-mediated suppression of hepatic glucose production and muscle glucose uptake. Metformin also exerts non-insulin-dependent effects on these tissues, including reduced fatty acid oxidation and increased anaerobic glucose metabolism by the intestine. FA, fatty acid f, increase i decrease. 

Metformin Renal or liver disease any predisposition to hypoxia Gastro intestinal upsets risk of lactic acidosis if wrongly prescribed Creatinine, Hb or Vit B12b... 

A class of drug derived from guanidine, including metformin and phenformin. Metformin is currently widely used in humans for the treatment of type 2 diabetes. Phenformin was formerly also widely used but was withdrawn because of problems with lactic acidosis. 

Under certain circumstances, and very rarely, the inhibition of gluconeogenesis by metformin may suppress lactic acid metabolism and precipitate a potentially fatal lactic acidosis. Impairment of renal function, liver disease, alcoholism, conditions that give rise to increased lactate production (e.g. congestive heart failure, infections) are therefore contraindications for the application of metformin. 

Oral formulations of metformin are rapidly and completely absorbed. The agent is poorly bound to plasma proteins its duration of action is determined exclusively by renal elimination. Higher concentrations of metformin than in most tissues are found in the intestinal mucosa, giving tise to common side effects (irritation, diarrhoea etc.). 

Zhou G, Myers R, Li Y et al (2001) Role of AMP-activated protein kinase in mechanism of metformin action. J Clin Invest 108 1167-1174... 

Type 2 diabetes adjunct to metformin when adequate results are not achieved with either drug alone adjunct to insulin in stabilization of certain individuals with type 1 diabetes... 

Type 2 diabetes in combination with metformin to improve glycemic control Type 2 diabetes in combination with metformin to improve glycemic control... 

Other combination options Metformin or a Sulfonylurea plus Acarbose/Miglitol, or Pioglitazone/ Rosiglitazone or Repaglinide (with metformin), or Insulin... 

Metformin sensitizes die liver to circulating insulin levels and reduces hepatic glucose production. 

Lactic acidosis (buildup of lactic acid in the blood) may also occur with die administration of metformin. Although lactic acidosis is a rare adverse reaction, its occurrence is serious and can be fatal. Lactic acidosis occurs mainly in patients with kidney dysfunction. Symptoms of lactic acidosis include malaise (vague feeling of bodily discomfort), abdominal pain, rapid respirations, shortness of breath, and muscular pain. In some patients vitamin B12 levels are decreased. This can be reversed with vitamin B12 supplements or with discontinuation of the drug therapy. Because... 

Metformin is contraindicated in patients with heart failure, renal disease, hypersensitivity to metformin, and acute or chronic metabolic acidosis, including ketoacidosis. The drug is also contraindicated in patients older than 80 years and during pregnancy (Pregnancy Category B) and lactation. 

The drug is used cautiously during surgery. Metformin use is temporarily discontinued for surgical procedures. The drug therapy is restarted when the patient s oral intake has been resumed and renal function is normal. 

There is a risk of acute renal failure when iodi-nated contrast material that is used for radiological studies is administered with metformin. Metformin therapy is stopped for 48 hours before and after radiological studies using iodinated material. Alcohol, amiloride, digoxin, morphine, procainamide, quini-dine, quinine ranitidine, triamterene, trimethoprim, vancomycin, cimetidine, and furosemide all increase the risk of hypoglycemia. There is an increased risk of lactic acidosis when metformin is administered with the glucocorticoids. 

BIGUANIDES. The nurse gives metformin two or three times a day with meals. If the patient has not experienced a response in 4 weeks using the maximum dose of metformin, the primary care giver may add an oral sulfonylurea while continuing metformin at the maximum dose. Glucophage XR (metformin extended release) is administered once daily with the evening meal. 

MANAGING LACTIC ACIDOSIS. When taking metformin, the patient is at risk for lactic acidosis. The nurse monitors die patient for symptoms of lactic acidosis, which include unexplained hyperventilation, myalgia, malaise, gastrointestinal symptoms, or unusual somnolence If the patient experiences these symptoms, the nurse should contact the primary care provider at once. Elevated blood lactate levels of greater than 5 mmol/L are associated with lactic acidosis and should be reported immediately. Once a patient s diabetes is stabilized on metformin therapy, the adverse GI reactions that often occur at the beginning of such therapy are unlikely to be related to the drug therapy. A later occurrence of GI symptoms is more likely to be related to lactic acidosis or other serious disease. 

Metformin—there is a risk of lactic acidosis when using this drug. Discontinue die drug therapy and notify the health care provider immediately if any of the following should occur respiratory distress, muscular aches, unusual somnolence, unexplained malaise, or nonspecific abdominal distress. 

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