Antidiabetic Concept Lab Summary for Exam

Antidiabetics Concept Lab Physiology of Blood Sugar Regulation Glucose is the body’s primary source of energy. In a healthy individual, two hormones secreted by cells in the Islets of Langerhans region of the pancreas stabilize blood sugar levels: glucagon and insulin. The Pancreas The pancreas is the principal site of blood sugar regulation in the body and has both endocrine and exocrine functions. It secretes enzymes to break down proteins, lipids, carbs and acids in food. Additionally, alpha and beta cells of the Islets of Langerhans region of the pancreas produce the hormones insulin and glucagon. The Pancreas: Glucagon Alpha cells in the pancreas produce the hormone glucagon in response to falling blood sugar levels. Glucagon binds to receptors in the liver, stimulation the conversion of stored glycogen into glucose. Glucose is then released into the blood, raising blood sugar levels. The Pancreas: Insulin Beta cells in the Islets of Langerhans region of the pancreas release the hormone in response to rising blood sugar levels. Insulin is a hormone that allows the body’s cells to absorb glucose from the bloodstream to use as an energy source. Insulin binds to receptors in the body’s cells, signaling the glucose transporter 4 (GLUT4) to allow glucose into the cell. Insulin is sometimes described as a “key” that allows glucose into the body’s cells. Pathophysiology of Type 2 Diabetes Diabetes mellitus is a group of diseases that occur when blood sugar levels remain high for a prolonged period. The distinct mechanisms resulting in chronic high blood sugar characterize each type of diabetes. Insulin Resistance Type 2 diabetes is characterized by insulin resistance due to desensitize insulin receptors in the body’s cells. When blood sugar levels and insulin production rates remain elevated fr a prolonged period, cells can become desensitized to the effect of insulin, making it difficult for the body’s cells to use glucose. This desensitization leads to even higher blood sugar levels. This increased production without corresponding cell response can lead to beta cell death through a process called apoptosis. This process leads to a depletion of the population of pancreatic beta cell. Pharmacotherapy of Type 2 Diabetes Pharmacological intervention is considered when lifestyle changes such as specialized diets and exercise fail to bring blood sugar within safe levels. Efficacy of particular type 2 diabetes treatments is determined by A1C (glycated hemoglobin) tests, which provide an average of an individual’s blood glucose levels over a series of months. This lab focuses on six of the most effective oral medications used to treat type 2 diabetes. Pharmacotherapy: Metformin One med, metformin, is widely considered the preferred first-line pharmaceutical intervention for patients with type 2 diabetes. Metformin is preferred because of its high efficacy, low risk of hypoglycemic effects and lower cost; may also help promote weight loss. Metformin is a biguanide, an organic compound with antihyperglycemic effects. Mechanism of Action: Metformin While its molecular MOA is incompletely understood, it is known that metformin reduces fasting and post-meal glucose levels by decreasing glucose production in liver. Metformin also helps reverse insulin resistance, allowing cells to use glucose. Effects: Metformin Metformin reduces glucose production in the liver, lowering the amount of glucose introduced to the blood. It also helps sensitize insulin-resistant cells to insulin, allowing cells to use glucose at a normal rate. GI issue, such as diarrhea, are among the common adverse effects reported with metformin use. Summary: Metformin Metformin: ● Is the first-line drug for treating type 2 diabetes ● Lowers blood glucose levels by reducing glucose production in the liver and reversing insulin resistance Adverse effects of metformin include: nausea vomiting, abdominal discomfort, taste disturbance, diarrhea, anorexia, headache, dizziness, agitation and fatigue Pharmacotherapy: Other Oral Antidiabetic Agents If, after approximately 3 months, metformin alone does not bring a patient to within an A1C target, other agents may be tried as monotherapies or in combination with metformin and other drugs to bring blood sugar within safe levels. Pharmacotherapy: SGLT-2 Inhibitors SGLT-2 inhibitors are a relatively new drug used for the treatment of type 2 diabetes in adults. SGLT-2 inhibitors reduce blood sugar by excreting glucose in the urine. SGLT-2 inhibitors used to treat type 2 diabetes include: Dapagliflozin, Empaglifozin, Canagliflozin, Ipragliflozin, Tofoglifozin, Sergliflozin etabonate Mechanism of Action: SGLT-2 Inhibitors In the kidneys, the SGLT-2 transporter reabsorbs glucose within the renal proximal tubule. SGLT-2 inhibitors compete with this transporter to reduce the amount of absorbed glucose. Unabsorbed glucose is excreted in the urine. Effects: SGLT-2 Inhibitors Prevent glucose reabsorption into the blood in the renal proximal tubule of the kidneys, lowering overall blood glucose levels. Glucose is excreted in the urine. UTI’s are common adverse effect reported with SGLT-2 use. Summary SGLT-2 Inhibitors ● Are relatively new drug used to treat type 2 diabetes ● Lower blood glucose levels by reducing the amount of glucose reabsorbed in the kidneys ● Glucose is excreted in the urine; UTI’s are a common adverse effect Adverse effects include: KETOACIDOSIS, UTI’s, candida vulvovaginitis, HYPOGLYCEMIA Pharmacotherapy: Thiazolidinediones (TZD’s) are another oral drug used to treat type 2 diabetes. They are often used in combination with metformin, but they can also be used as a monotherapy. TZD’s used to treat DM2 include: Pioglitazone, rosiglitazone Mechanism of Action: Thiazolidinediones TZD’s lower insulin resistance within muscle and fat cells. They combat insulin resistance by increasing the storage of fatty acids, causing cells to be more dependent on glucose to produce energy. Like metformin, TZD’s also reduce the amount of glucose produced by the liver. Effects: The intended effect is to increase the storage of fatty acids, causing cells to be more dependent on carbs, like glucose to produce more energy. This effect reduces insulin resistance. Edema water retention, and weight gain are adverse effects reported with thiazolidinedione use. Summary: Thiazolidinediones ● Are another oral agent used to treat type 2 diabetes, either as a monotherapy or in combination with other drugs ● Lower insulin resistance by increasing storage of fatty acids, making cells more dependent on glucose as an energy source. ● Weight gain is a common adverse effect Adverse effects include: Upper resp infection, myalgia, headache, edema, weight gain, HYPOGLYCEMIA, HEPATOTOXICITY, BONE FRACTURES, HEART FAILURE, MI Pharmacotherapy: Alpha-Glucosidase Inhibitors (AGI’s) are another oral agent used to treat type 2. These drugs are generally well-tolerated and can be used as a monotherapy or in combination with other drugs. Alpha-glucosidase inhibitors used to treat type 2 include: Acarbose, miglitol, voglibose MOA: AGI’s Compete with complex carbs at the site of alpha-glucosidase enzymes in the small intestine. These enzymes are responsible for breaking down complex carbs into monosaccharides, such as glucose. Effects: AGI’s The intended effect is to slow the breakdown of complex carbs into glucose within the small intestine. Abdominal issues, such as diarrhea and flatulence are common adverse effects associated with AGI use. Summary: AGI’s ● Are another oral agent to treat type 2, either as monotherapy or combination ● Lower glucose levels by inhibiting the breakdown of complex carbs into glucose within the small intestine ● Abdominal issues, such as diarrhea and flatulence are common adverse effects ● Prevent alpha-glucosidase enzymes from breaking down complex carbohydrates into glucose Adverse effects include: Diarrhea, flatulence, abdominal distention, HYPOGLYCEMIA Pharmacotherapy: Sulfonylureas and Meglitinides Two additional oral agents used in the treatment of type 2 are sulfonylureas and meglitinides. Though these drugs are sometimes utilized as monotherapies, combination therapy with metformin is common. Sulfonylureas used in the treatment of type 2 include: Chlorpropamide, tolazamide, tolbutamide Meglitinides used in the treatment of type 2: Nateglinide, repaglinide MOA: Both work by directly stimulating the production and release of insulin from pancreatic beta cells through the inhibition of the K+/ATP channel. The binding duration of meglitinides, however, tends to be shorter, which also shortens their effect. Effects: Lower blood sugar by producing more insulin to overcome insulin resistance and allow the body’s cells to u se more glucose as an energy source. Summary: ● Are two additional drugs used to treat type 2, either as monotherapy or combination ● Lower blood glucose levels by stimulation the production of more insulin to allow cells to use glucose ● Are differentiated by their duration times (meglitinides have a shorter effect duration Adverse effects of sulfonylureas: Nausea, heartburn, dizziness, headache, drowsiness, HYPOGLYCEMIA, CHOLESTATIC JAUNDICE, BLOOD DYSCRASIAS. Adverse effects of meglitinides: HYPOGLYCEMIA, ANAPHYLAXIS, PANCREATITIS