Antidiabetic drugs classification and mechanism of action pdf

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antidiabetic drugs classification and mechanism of action pdf

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Diabetes mellitus is a chronic, progressive, incompletely understood metabolic condition chiefly characterized by hyperglycemia. Impaired insulin secretion, resistance to tissue actions of insulin, or a combination of both are thought to be the commonest reasons contributing to the pathophysiology of T2DM, a spectrum of disease originally arising from tissue insulin resistance and gradually progressing to a state characterized by complete loss of secretory activity of the beta cells of the pancreas. T2DM is a major contributor to the very large rise in the rate of non-communicable diseases affecting developed as well as developing nations.

Oral Hypoglycemic Drugs

Antidiabetic drugs are drugs that treat diabetes—a condition marked by either failure of insulin production, or reduced sensitivity to insulin,. There are two common forms of diabetes, type 1, which is marked by failure of insulin production, and type 2 which is marked by reduced sensitivity to insulin. Type 2 has been associated with obesity , and has been seen with increasing frequency as the weight of the population of developed nations has increased.

Type 1 normally requires insulin as the basis of treatment, because the pancreas is unable to produce insulin. Although the treatment of type 2 diabetes should begin with a program of diet and exercise and a focus on weight loss , several different classes of drugs have been developed to treat the condition.

These can increase insulin release, help sensitize the cells to insulin, or lower the glucose spikes that occur after meals. Insulin is a hormone, secreted by the islet cells of the pancreas, which causes other cells to take in glucose. In type 1 diabetes, the islet cells might be insufficient or even absent, and the body might have produced antibodies to these cells. Because the body cannot produce insulin, oral drugs will be ineffective, and the insulin must be replaced by injection.

Since the goal is to maintain blood glucose levels within a fairly narrow range, a large number of modified versions of insulin have been developed with different durations of action. Patients requiring insulin must monitor their blood sugar on a regular basis, and use various combinations of insulin in order to maintain appropriate levels. Oral antihyperglycemic antidiabetic drugs may be useful in treatment of patients with type 2 diabetes, although many of these patients may progress to needing insulin.

There are no generally recognized protocols for selecting which class of drug to use for initial therapy. For mild cases, physicians will base their judgment on past experience, however, diabetologists conduct detailed testing and base drug selection on the precise mechanism of action of the drug. Although many patients who start on oral drugs eventually progress to needing insulin, a Russian study showed that a regimen of oral therapies resulted in comparable glucose control and less weight gain than a combination of oral drugs and insulin.

This was a short term study and the conclusions are not definitive, but further study is indicated. While all these drugs work in a similar manner, acetohexamine, chlorpropamide, tolazamide and tobutamide are termed 1st generation, and have a higher risk of unwanted side effects.

Their use in therapy has largely been supplanted by the second generation drugs, glipizide, glyburide and glimiperide. Patients who are severely obese or with fasting blood sugar levels in excess of milligrams per deciliter are unlikely to respond well to any of the oral drugs.

Acarbose and miglitol act not by affecting insulin secretion or sensitivity, but by delaying absorption of dietary carbohydrates. This lowers the blood sugar spike that normally follows a meal.

These drugs can be used alone, or in combination with other classes of antidiabetic drugs. Pramlintide acetate injection is used in combination with insulin for either diabetes type 1 or type 2, for patients who cannot control their blood sugar adequately with mealtime insulin injections alone.

Pramlintide mimics the effects of amylin which is normally secreted by the pancreas at the same time as insulin. The physiologic effects are to reduce glucagon release glucagon, stored in the liver, is a stored form of glucose, and its release raises glucose levels , slow the stomach's emptying time to reduce the rate at which carbohydrates are absorbed, and produce a feeling of fullness which reduces overall food intake. This drug is limited to use by patients who are already insulin dependent, although the dosing schedule is different for diabetes type 1 and type 2.

Exenatide is an injection used for patients with type 2 diabetes who are taking one or more oral drugs, but have not achieved adequate glycemic blood sugar control. Exenatide mimics the action of the incretins , a group of hormones secreted by the intestinal tract at the time food material enters the intestine.

Glucagon-like peptide-1 GLP-1 also stimulates the growth of insulin-producing cells and appears to lengthen the survival time of these cells, and slow the time of transit of food through the intestinal tract, which delays absorption of carbohydrates and reduces the after meal blood sugar spike.

Sitagliptin phosphate is a dipeptidyl peptidase-4 DPP-4 inhibitor that is believed to exert its actions in patients with type 2 diabetes by slowing the inactivation of incretin hormones. The incretins are secreted by the stimulation of the presence of food in the intestine, and they in turn stimulate the beta cells to produce more insulin. DPP-4 inactivates the incretins. By inactivating DPP-4, stigagliptin increases the levels of incretins, leading to increased insulin production.

The prolonged incretin level also lowers glucagon secretion from pancreatic alpha cells, leading to reduced glucose production by the liver. Stigaglitin can be use alone or in combination with an insulin sensitizer when diet and exercise alone have not provided adequate control of blood sugar levels. Metformin can be used alone or in combination with other drugs in the treatment of type 2 diabetes.

Metformin decreases glucose production, decreases the intestinal absorption of glucose, and improves insulin sensitivity in the cells of the body. With metformin therapy, insulin secretion remains unchanged, while fasting insulin levels and daylong plasma insulin response might actually decrease. One review of published studies indicated that starting metformin treatment during pre-diabetic states might prevent progression to diabetes.

Repaglinide and nateglinide are the meglitinide group and may be used either alone, or in combination with metformin or one of the drugs in the thiazolidinedione category. In patients whose blood sugar is inadequately controlled with metformin or a thiazolidinedione, a meglitinide may be added to, but not substituted for, those drugs.

Meglitinides lower blood glucose levels by stimulating insulin secretion from the pancreas. This action depends upon functioning beta cells in the pancreatic islets. Unlike sulfonylureas, the glitazones do not increase. They can be used alone or in combination with metformin, insulin, or a sulfonylurea. There is no fixed dosage regimen for the management of diabetes mellitus with any hypoglycemic agent.

Glycemic or blood sugar control should be monitored with the blood tests hemoglobin A1C or blood glucose levels to determine the minimum effective dose for the patient; to detect primary failure, i. Home blood glucose monitoring can also provide useful information to the patient and physician.

Short-term administration of glipizide extended-release tablets can be sufficient during periods of transient loss of control in patients usually controlled on diet. The following warnings are the most significant for anti-diabetic drugs. The absence of an entry in this section does not indicate safety, but that product specific references should be consulted for more detailed information.

These warnings are truncated from the official literature—see the full package insert for the complete text. All sulfonylureas can cause severe hypoglycemia, or low blood sugar. Proper patient selection, dosage, and instructions are important to avoid hypoglycemic episodes. Kidney or liver disease can elevate blood levels of the drug, and liver disease can also reduce the liver's ability to make new glucose gluconeogenesis.

Elderly, debilitated, or malnourished patients, and those with adrenal or pituitary insufficiency are particularly susceptible to the hypoglycemic action of glucose-lowering drugs. Hypoglycemia can be difficult to recognize in the elderly and in patients taking drugs known as beta blockers. Hypoglycemia is more likely to occur when calorie intake is too low, after severe or prolonged exercise, when alcohol is ingested, or when more than 1 glucose-lowering drug is used.

Pramlintide is used with insulin and has been associated with an increased risk of insulin-induced severe hypoglycemia, particularly in patients with type 1 diabetes.

When severe hypoglycemia associated with pramlintide use occurs, it is seen within 3 hours following a pramlintide injection. If severe hypoglycemia occurs while operating a motor vehicle, heavy machinery, or while engaging in other high-risk activities, serious injuries can occur.

Appropriate patient selection, careful patient instruction, and insulin dose adjustments are critical elements for reducing this risk. There have been reports of serious allergic and hypersensitivity reactions in patients treated with sitagliptin.

These reactions include anaphylaxis life threatening allergic reaction , angioedema swelling of the skin and mucousmembranes , and Stevens-Johnson syndrome, an allergic reaction that results in the sloughing of skin. In such cases, promptly stop sitagliptin, assess for other potential causes, monitor and treat, and initiate alternative treatment for diabetes. Lactic acidosis may also occur in association with a number of conditions, including diabetes mellitus itself, and whenever there is significant reduction in blood flow and oxygen to the tissues.

Thiazolidinediones cause or worsen congestive heart failure CHF in some patients. If these signs and symptoms develop, the doctor should manage the heart failure appropriately and consider discontinuation or dose reduction of the drug. The administration of oral hypoglycemic drugs has been reported to be associated with an increased risk of death from heart disease as compared to treatment with diet alone or diet plus insulin.

This warning is based on the study conducted by the university group diabetes program UGDP , a clinical trial designed to whether these drugs reduced heart and vascular disease in diabetics.

As with all drugs, antidiabetic agents should not be used in patients who have shown hypersensitivity to the drug or any of the components. These drugs have been widely used, and a very large number of adverse effects have been ascribed to most of them. Consult specialized references for detailed information.

Anemia —A reduction in the number of red blood cells in the blood stream causing too little oxygen to reach tissues and organs. Carbohydrate —A collective term for sugars and starches that can be broken down to glucose. The common factor is that both conditions cause frequent urination. When used alone, the term refers to Diabetes Mellitus, in which the body cannot control the amount of sugar in the blood.

The name derives from the fact that sugar appears in the urine, giving the urine a sweet odor. Pancreas —An organ, located behind the lower part of the stomach. It secretes insulin as well as other enzymes that play a role in food digestion. Protocol —A detailed plan for how a disease or condition should be treated, including which drugs should be used first. Metformin has been associated with diarrhea , nausea, gastric pain , vitamin B 12 malabsorption.

The drug can increase weight loss. Alpha-glucosidase inhibitors commonly cause flatulence and bloating at the initiation of treatment, but this often declines over time. These drugs should be taken according to a fairly rigid schedule. They must be coordinated with meals. Although metformin associated lactic acidosis is extremely rare, caregivers should be familiar with the symptoms and observe patients carefully.

Mar 1, —5. Hornick, T, Aron DC. February 75 2 —8. February 2 — Feb 7, 6 — Malesker, MA. Feb, 28 2 — Huang, ES. November 3 4 —3. February 24 2 — Jan-Feb 22 1 :1—9. November 70 11 —

Anti-diabetic medication

Drugs used in diabetes treat diabetes mellitus by altering the glucose level in the blood. With the exceptions of insulin , exenatide , liraglutide and pramlintide , all are administered orally and are thus also called oral hypoglycemic agents or oral antihyperglycemic agents. There are different classes of anti-diabetic drugs, and their selection depends on the nature of the diabetes, age and situation of the person, as well as other factors. Diabetes mellitus type 1 is a disease caused by the lack of insulin. Insulin must be used in type 1, which must be injected. Diabetes mellitus type 2 is a disease of insulin resistance by cells.

Mechanism of Action for the Drug Class. Improves glucose tolerance by lowering both basal and postprandial plasma glucose. Decreases hepatic glucose.

The Management of Type 2 Diabetic Patients with Hypoglycaemic Agents

Antidiabetic drugs are drugs that treat diabetes—a condition marked by either failure of insulin production, or reduced sensitivity to insulin,. There are two common forms of diabetes, type 1, which is marked by failure of insulin production, and type 2 which is marked by reduced sensitivity to insulin. Type 2 has been associated with obesity , and has been seen with increasing frequency as the weight of the population of developed nations has increased. Type 1 normally requires insulin as the basis of treatment, because the pancreas is unable to produce insulin. Although the treatment of type 2 diabetes should begin with a program of diet and exercise and a focus on weight loss , several different classes of drugs have been developed to treat the condition.

Antidiabetic drugs

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Oral hypoglycemic drugs are used only in the treatment of type 2 diabetes which is a disorder involving resistance to secreted insulin. Type 1 diabetes involves a lack of insulin and requires insulin for treatment. There are now four classes of hypoglycemic drugs:. These drugs are approved for use only in patients with type 2 diabetes and are used in patients who have not responded to diet, weight reduction, and exercise. They are not approved for the treatment of women who are pregnant with diabetes. Sulfonylureas may also have extra-pancreatic effects, one of which is to increase tissue sensitivity to insulin, but the clinical importance of these effects is minimal.

Antidiabetic Drugs. Insulin, Non Insulin Antidiabetic. Drugs. Assistant Prof. The classification of diabetes Mechanisms of action of the sulfonylureas. 1.


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