Glucophage also known as metformin (generically) is a medicine which is administered orally and assists to regulate blood sugar levels. It is used to treat type2 diabetes in children and adults or the commonly called non-insulin-dependent diabetes. What’s more, Glucophage is utilized in the prevention of diabetes in a vulnerable population, and weight gain management resulting from psychoses medications side effects. Glucophage is infrequently utilized along with other drugs, such as insulin even though it cannot treat diabetes type 1. Insulin is produced by the pancreas; this hormone is used to regulate the levels of blood. It achieves this by decreasing the levels of glucose synthesized by the liver and activating the elimination of glucose from the blood by fat and muscle tissues. Consequently, the blood glucose level decreases. Diabetes results because of low production of insulin which leads to high production of glucose from the liver and low uptake of insulin in muscle and fat tissues (Jjemba 60). Glucophage as a rule escalates the sensitivity of fat, muscle, as well as dissimilar tissues, to the uptake of insulin. Those actions cause blood sugar to decrease.
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About fifty years back Glucophage together with exercise and diet has assisted type 2 diabetic patients throughout the world. The invention of Glucophage has helped the patient lower the sugar level more importantly it has been a safe medication for the patients. During that time, the invention of Glucophage was a unique and significant development in the treatment of type 2diabetes mainly because it prevented the body to produce excess insulin. However, it assisted the body to respond positively to the amount of insulin produced in the body itself, to reduce the amount of glucose produced by the liver, and reduce the absorption of sugar from the intestines. Thus this drug together with exercise and diet assisted in regulating blood sugar levels (O’Keefe et al 177).
Glucophage was introduced in 1958 by a French pharmacist called Jan Aron, together with Doctor Jeane Sterne. They guided a team that developed the most significant type 2 diabetes drug. As a result of their faith and determination, they gave new hope to patients with type 2 diabetes (86 Due to conviction that the drug could decrease blood glucose amongst the patient, Aron decided to launch the drug in France by late 1958. In 1958, December 11, Glucophage was authorized by the Ministry of Health in France. During that time, the concept of a type 2 drug that inhibited the body from producing more insulin raised some speculation. Nevertheless, the French medical group promoted the drug by word of mouth. As a result, Glucophage started to be recognized as a drug which assisted in decreasing blood sugar among type 2 diabetes patients. Consequently, the drug‘s favorable status grew very rapidly. After two years, Aron Laboratories validated a new finding concerning Glucophage. Doctor Jeane Sterne noted that for those patients whose blood glucose could not be controlled using Glucophage alone, combining sulfonylurea agent and Glucophage caused the level of blood glucose to decrease in some patients. Currently, Glucophage is commonly used together with sulfonylurea. Around 1969, release of 850 mg tablet promoted administration of the drug in higher doses when required. Around mid 1980s, Glucophage was found in most pharmacies throughout the world, apart from the United States. An organization called LIPHA was in charge of Glucophage by 1980s, it started the procedures of acquiring approval of the drug in America. After about eight years of clinical trials and legalizing processes, the drug was approved for marketing in America. Shortly it became the major prescribed diabetes medication in America. Around 2000, Food and Drug Administration (FDA) based in America endorsed Glucophage XR. This was a once daily dose of original Glucophage (Wolfe et al 89).
Description and System Performance
Glucophage tablets are not pharmacologically or chemically related to other groups of drugs under oral antihyperglycemic classification. Glucophage is insoluble in ether, acetone, and chloroform and soluble in water. The tablets consist of 100mg, 850mg, and 500mg of metformin hydrochloride. Every tablet is made of two inactive ingredients magnesium stearate and providone. Glucophage XR system consists of double-fold matrix of hydrophilic polymer. This polymer controls drug release, and further amalgamates with metformin hydrochloride to form the inner phase. Following drug taking, the gastrointestinal tract (GIT) fluid goes through the tablet. Consequently, the polymers turn out to be hydrated, thereby bulging. Through the process of diffusion, the drug is liberated gradually in dosage form. This occurs via the gel matrix which basically does not dependent on the pH. However, the hydrated polymer is floppy and it’s supposed to be disintegrated through the typical process of peristalsis which occurs in the gastrointestinal tract. The tablet constituents are purely inert and are left intact throughout the peristalsis process. Excretion is done via feces, depicting hydrated, soft mass.
Mechanism of Action
Glucophage acts as antihyperglycemic agent that promotes glucose tolerance among type 2 diabetes patients. They achieve this by reducing postprandial and basal plasma glucose. Glucophage’s pharmacologic modes of action are different from other oral antihyperglycemic drugs. In contrast to sulfonylureas, Glucophage never produces hypoglycemia in normal individuals or even type 2 diabetes patients, and also it never cause hyperinsulimemiua. Patients under Glucophage therapy, the secretion of insulin is not altered whereas plasma insulin response and the levels of fasting insulin could decrease (Bristol-Myers Squibb Company 1).
Absorption and Bioavailability
Food has been reported to delay the absorption of Glucophage to some extent, about forty percent of plasma concentration in the lower mean peak is observed. Absorption of metformin from Glucophage XR was also reported to increase by about fifty percent if administered with food. In addition, low and high fat meals were recorded to have similar effect on Glucophage XR pharmacokinetics. Its absorption is moderately slow and could take more than six hours. Typically the glucophage is excreted via urine, and renal clearance rate is normally high, just about 450 mL is/ min. The initial excretion is fast with half life ranging between 1.7 to about 3 hours. The lethal excretion phase is slow and ranges from four to five percent of the assimilated dose, its half life varies between nine to seventeen hours. Normally, Glucophage is never metabolized; the major areas of concentration are salivary glands and intestinal mucosa. At steady state, the plasma concentration varies from one to two mcg/mL. Some drugs have been reported to affect absorption of Glucophage (Bristol-Myers Squibb Company 2).
Dosage and administration
For diabetic patients, the main aim is to achieve a minimum dose which would decrease blood glucose sufficiently. That targets to maintain the glycemic levels to be near the normal levels. To reduce gastrointestinal symptoms, a lower dose is recommended for the start and the dose is increased steadily. For certain duration of time, the patients might respond slowly to oral hypoglycemic therapy because their diabetic state tends to be weak. Therefore, patients ought to be monitored with frequent laboratory and clinical examinations such as glycosylated hemoglobin and blood glucose verifications. This helps to identify secondary and primary failure and the minimum efficient dosage. For patients whereby the maximum dose is unsuccessful and does not efficiently decrease blood sugar, therapeutic options should be used. The usual dose is 850mg, administered 3 to 2 times daily or 500mg for 3 or 4 times daily. The utmost dose does not go above 2.55 g per daily. In order to reduce gastric intolerance like vomiting and nausea, Glucophage ought to be taken together with food. If the patient did not remember to take the tablets, one is not supposed to take double dose to compensate, however one should take the next dose the normal time. Concerning treatment of overdose, there is limited accessible information. However, adverse side effects are expected such as vomiting, nausea, epigastric discomfort, dizziness, malaise, headache, weakness and diarrhea. If the symptoms continue, lactic acidosis is supposed to be excluded (Joslin and Kahn 699). The dose should be terminated and correct supportive therapy introduced. Hypoglycemic was recorded in about ten percent of the studies although no relationship with Glucophage was established. Lactic acidosis was recorded in around thirty two percent cases. Under suitable hemodynamic conditions, Glucophage is dialyzable and the clearance rate is about 170mL/min. Thus, hemodialysis could be helpful to eliminate accumulated drug in case Glucophage overdose was detected (Sanofi-aventis 4).
Contradictions and precautions
Glucophage has been reported to affect patients with different conditions. For instance, patients with renal dysfunction or renal disease that might also be caused by various conditions like septicemia, cardiovascular collapse or myocardial infarction. Others include evident metformin hydrochloride hypersentivity and metabolic acidosis such as diabetic ketoacidosis.
Lactic acidosis is not common but it’s an adverse metabolic disorder which can arise as a result of Glucophage accumulation. If it occurs, it has adverse effects in about fifty percent of the cases. Nevertheless, there are few cases where lactic acidosis has been observed in patients using metformin. Mostly such cases have occurred to patients suffering from diabetes and have renal insufficiency. The increase in the level of lactic acidosis depends on an increase in the level of renal dysfunction and the patient’s age. Therefore, lactic acid risk could be regulated through frequent assessment of renal function among patients using Glucophage. Mostly, treatment of elderly patients should involve close supervision of renal function. In patients suffering from dehydration, sepsis or hypoxemia, Glucophage administration should be suspended promptly. This is because any alteration of renal function could affect clearing of lactate. Individuals (patients) under Glucophage medication ought to avoid taking alcohol. This is because it inhibits function of Glucophage on lactate metabolism. Therefore, patient taking Glucophage and has lactic acidosis disorder should seek medical support and the drug should be terminated immediately (Cassel 689). This drug is typically eliminated from the body through the kidney, and thus the possibility of lactic acidosis accumulation increases with the alteration of renal function. Hence, patients who have high levels of creatine in comparison to their age are not supposed to take Glucophage. For the elderly the renal function should be examined regularly in order to determine the effective glycemic minimum dose.
Warnings and Administration
Before beginning Glucophage therapy, renal function should be monitored and confirmed to be normal. In cases where renal dysfunction is anticipated, the renal function must be examined and glucophage medication terminated. Concomitant drugs that might influence Glucophage disposition or renal function like cationic drugs which are secreted through renal tubular ought to be employed carefully. Intravascular researches that utilize iodinated materials have been linked to renal dysfunction and could result in lactic acidosis among patients utilizing Glucophage. Hence for patients scheduling such studies, Glucophage administration should be terminated during that time and reintroduced after reassessment of renal function is proved to be okay. Hypoxic states which has different causes and other disorders like hypoxemia are related to prerenal azotemia and lactic acidosis. If such disorders arise in patients under Glucophage therapy, then the therapy must be terminated immediately. Glucophage therapy should be withheld briefly if any surgical process is taking place and is not supposed to be resumed until renal function is assessed to be normal and other oral drugs have been restarted. Patient suffering from hepatic dysfunction ought to avoid glucophage medication. Patient who had had well regulated type 2 diabetes using Glucophage and then develops some clinical abnormalities must be examined for lactic acidosis or ketoacidosis. If there is evidence of any of the disorders, then Glucophage intake should be terminated immediately. Hypoglycemia could also be caused by lack of caloric intake. This is when tedious exercises is not balanced by more caloric intake or when one is using other concomitant agents causing a decrease of blood glucose. Malnourished patients, alcohol intoxication, elderly, individuals suffering from pituitary or adrenal dysfunction are mainly prone to hypoglycemic disorders. If a patient who is under diabetic medication is exposed to unfavorable conditions such as trauma, surgery, fever, or infection, a brief loss of glycemic control is observed (Howley and Franks 314).
There are different drugs which could be used together with Glucophage. Some cause pharmacological changes whereas others have no effect. For instance, cationic drugs such as: ranitidine, morphine, quinine and others. They are secreted via renal tubular and normally compete with Glucophage for the tubular transport system. There are reported cases of normal individuals whereby oral cimetidine was noted to interact with Glucophage in multiple and single doses. However, Glucophage did not influence cimetidine pharmacokinetics. Hence it’s important to monitor such cationic drugs in patients under Glucophage therapy. Furosemide, when healthy individuals were administered furosemide- Glucophage, it was observed that the pharmacokinetics of both drugs was altered after co administration of the dose. Some drugs were noted to cause hyperglycemia and could result altered glycemic control. Such drugs include corticosteroids, thiazides, estrogens, oral contraceptives, some diuretics, nicotinic acid, and phenytoin (Stargrove et al 580).If those drugs are taken by patient under Glucophage therapy, the patient is supposed to be monitored for lack of blood sugar control.
In addition, if those drugs are terminated, then there should be close monitoring for hypoglycemia. Another study involving healthy individuals showed that Glucophage pharmacokinetic was not interfered when administered with ibuprofen, propranolol and metformin. Glucophage is moderately bound to plasma protein hence it rarely interact with protein bound drugs like sulfonamides, salicylates, probenecid and chloramphenical in contrast to sulfonylureas that are entirely bound to serum proteins. The excretion rate of phenprocoumon which is anticoagulant was noted to increase with twenty percent when used together with Glucophage. Thus patients using phenprocoumon and other anticoagulants are supposed to be examined closely if the two drugs are administered concurrently. In such incidences, there is likelihood of prothrombin time increase and individuals are susceptible to hemorrhage (Rattan and Kassem 140)
Use of Glucophage during pregnancy is not recommended. Present research argued that unusual blood sugar levels for pregnant mothers are linked to congenital abnormalities. Nevertheless, there was an agreement among professionals that insulin could be administered to pregnant mothers to sustain blood sugar level relatively normal. For the lactating mothers, they should be monitored carefully, and a judgment should be done either to terminate the drug or to terminate nursing, considering the impact of the medication to the mother. On geriatrics there has not been significant research indicating the effect of Glucophage therapy between the young and the elderly. However, Glucophage is mainly excreted through the kidney, since the side effects of the drug is adverse in individuals with renal dysfunction, then Glucophage is supposed to be used by patients who have no renal impairment. Aging has been related to decreased renal function; therefore Glucophage therapy ought to be administered carefully among the elderly. One is supposed to be very cautious with dose selection and it must be based on frequent and careful assessment of the renal function. Normally patients who are elderly are not supposed to be administered maximum dose of the drug. Therefore it is important to be careful while prescribing Glucophage to any patient and the doctor need to know the history first (Sanofi-aventis 6).
Glucophage is one of the most commonly used drugs in treatment of diabetes type 2. The medication is recommended after exercise and dietary interventions have failed. The drug is preferred because of the few side effects and its cheap price. Glucophage is very effective in regulating blood glucose; it does this by decreasing amount of insulin produced by the body. In addition it helps the body to regulate its own sugar hence maintaining the balance. When the drug was first combined with exercise and proper diet, a solution was found for type 2 diabetes. However, the drug has some associated adverse effects which mostly arise when one has other body disorders. For instance individuals with renal dysfunction are prone to lactic acidosis if they use Glucophage. The drug should be administered after the doctor has known the history of the patients because most side effects arise indirectly.
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