Pharmacology - DRUGS FOR DIABETES (MADE EASY)

Summary

This lecture covers the different drugs used to treat diabetes, focusing on insulin and its analogs, amylin mimetics, incretin mimetics, and oral antidiabetic agents. It explains how insulin regulates blood glucose, the role of different insulin types (rapid-acting, intermediate, and long-acting), and the side effects associated with insulin use. The lecture also discusses medications like GLP-1 mimetics, DPP-4 inhibitors, sulfonylureas, and other classes of oral antidiabetic drugs, explaining their mechanisms, benefits, and common side effects, such as hypoglycemia and weight gain.

Takeaways

• 😀 Diabetes mellitus is a chronic disorder characterized by high blood glucose levels due to inadequate insulin production or insulin resistance.
• 😀 Type 1 diabetes occurs when insulin-producing cells are destroyed, while Type 2 diabetes involves insulin resistance and gradual insulin deficiency.
• 😀 Insulin is a peptide hormone secreted by pancreatic beta cells, which facilitates glucose uptake into cells for energy production or storage.
• 😀 When blood glucose levels drop, glucagon, released by alpha cells in the pancreas, stimulates the breakdown of glycogen to raise blood glucose levels.
• 😀 Insulin can be administered via subcutaneous injections, and its preparations are categorized based on their onset and duration of action: rapid-acting, intermediate-acting, and long-acting.
• 😀 Rapid-acting insulins (e.g., insulin Lispro, Aspart, and Glulisine) have a quick onset and short duration, while long-acting insulins (e.g., Detemir, Glargine, Degludec) have slow onset and long duration.
• 😀 Hypoglycemia (low blood glucose) is a common side effect of insulin therapy, along with lipodystrophy (fatty tissue changes at injection sites).
• 😀 Pramlintide is a synthetic amylin analog that helps delay gastric emptying, suppress glucagon secretion, and promote satiety, allowing for reduced insulin doses.
• 😀 GLP-1 mimetics (e.g., Exenatide, Liraglutide) mimic the effects of incretin hormones, promoting insulin secretion, slowing gastric emptying, and aiding in weight loss.
• 😀 DPP-4 inhibitors (e.g., Alogliptin, Sitagliptin) work by inhibiting the enzyme responsible for degrading GLP-1, thereby enhancing insulin secretion and reducing glucagon release.
• 😀 Sulfonylureas (e.g., Glimepiride, Glyburide) stimulate insulin release by binding to ATP-sensitive potassium channels, although they may cause hypoglycemia and weight gain.
• 😀 Biguanides, such as Metformin, lower blood glucose by reducing hepatic glucose production, increasing insulin sensitivity, and slowing glucose absorption from the intestine.
• 😀 Thiazolidinediones (e.g., Pioglitazone, Rosiglitazone) activate PPAR-gamma, improving insulin sensitivity in tissues and reducing hepatic glucose production, but may cause weight gain and fluid retention.
• 😀 SGLT2 inhibitors (e.g., Canagliflozin, Dapagliflozin) reduce blood glucose by inhibiting glucose reabsorption in the kidneys, leading to increased urinary glucose excretion and mild osmotic diuresis.
• 😀 Alpha-glucosidase inhibitors (e.g., Acarbose, Miglitol) delay glucose absorption by inhibiting the enzyme responsible for breaking down carbohydrates in the intestines, but may cause gastrointestinal side effects like bloating and diarrhea.

Q & A

What are the two most commonly encountered types of diabetes?

The two most commonly encountered types of diabetes are Type 1 and Type 2 diabetes. Type 1 diabetes occurs when insulin-producing cells are destroyed, eliminating insulin production. Type 2 diabetes is characterized by insulin resistance and gradual insulin deficiency.

What is the role of insulin in the body?

Insulin is a peptide hormone produced by the beta cells of the pancreas. It facilitates the uptake of glucose into cells, where it is used for energy or stored as glycogen in the liver and muscles. Insulin helps lower blood glucose levels after meals.

How does glucagon function in the body?

Glucagon, released by alpha cells of the pancreas when blood glucose is low, works to raise blood glucose levels. It promotes the breakdown of glycogen in the liver into glucose, which is then released into the bloodstream.

Why is insulin usually administered by subcutaneous injection?

Insulin is a polypeptide that is susceptible to degradation in the gastrointestinal tract, so it cannot be taken orally. Therefore, it is typically administered through subcutaneous injection to ensure effective absorption into the bloodstream.

What is the difference between rapid-acting and long-acting insulin?

Rapid-acting insulins, like insulin Lispro, Aspart, and Glulisine, act within 30 minutes with a peak effect and duration of up to 5 hours. Long-acting insulins, like insulin Detemir and Glargine, provide a steady release of insulin with a duration of up to 24 hours or more and do not produce a peak effect.

What are some side effects associated with insulin use?

The most common side effect of insulin is hypoglycemia (low blood glucose). Another side effect is lipodystrophy, which can occur at the injection site if insulin is administered repeatedly in the same location.

What is Pramlintide, and how does it help with diabetes management?

Pramlintide is a synthetic analog of amylin, a peptide hormone that slows gastric emptying, suppresses postprandial glucagon secretion, and promotes satiety. It helps reduce insulin doses but may cause nausea and modest weight loss.

How do GLP-1 mimetics like Exenatide and Liraglutide work in treating diabetes?

GLP-1 mimetics are synthetic hormones that mimic the action of GLP-1, an incretin hormone. They stimulate insulin secretion, slow gastric emptying, and promote satiety, which can help with weight loss in diabetic patients. However, they may also cause GI side effects like nausea and vomiting.

What is the mechanism of action of DPP-4 inhibitors?

DPP-4 inhibitors, like Sitagliptin and Saxagliptin, work by inhibiting the enzyme DPP-4, which breaks down GLP-1 and GIP. By inhibiting this enzyme, these drugs prolong the activity of GLP-1 and GIP, enhancing insulin secretion, reducing glucagon release, and slowing gastric emptying.

What are the primary side effects of Metformin?

The most common side effects of Metformin, a biguanide, are gastrointestinal issues such as nausea, vomiting, diarrhea, and loss of appetite, which may lead to weight loss. It also carries a risk of lactic acidosis, particularly in patients with renal or heart failure.