Exam 1 Ch 41 Pancreatic Hormones & Antidiabetic Agents Flashcards
What is the most common complication that results from an intake of too much insulin? How does one counteract the adverse effect?
- Hypoglycemia results form excessive insulin effect
- Can cause brain damage due to hypoglycemia
- Prompt administration of glucose (sugar/candy by mouth, glucose by vein) or og glucagon (by intramuscular injection) is essential
What is the chemical class that most insulin secretagogues belong to?
Sulfonylureas
List the second-generation sulfonylureas.
Glyburide
Glipizide
Glimepiride
Unlike sulfonylureas, what do biguanides NOT cause?
Hypoglycemia
What type of oral antidiabetic are acarbose and miglitol and what do they do?
Acarbose and miglitol are alpha-glucosidase inhibitors that are carbohydrate analogs that act within the intestine to inhibit alpha-glucosidase
List the different classifications of insulin drugs for diabetes mellitus. (3)
1) Rapid, Short-Acting (lispro, regular)
2) Intermediate-acting (NPH, lente)
3) Slow, long-acting (glargine)
List the different classifications of noninsulin drugs for diabetes. (7)
1) Insulin secretagogues (glipizide)
2) Biguanides (metformin)
3) Alpha-glucosidase Inhibitors (acarbose)
4) Thiazolidinediones (Pioglitazone)
5) Amylin Analogs (Pramlintide)
6) Incretin Modulators ( GLP-1 Analog–exenatide and DDP-4 Inhibitor–sitagliptin)
7) SGLT2 Inhibitors (canagliflozin)
By what mechanism do sulfonylureas and meglitinides lower blood glucose?
They stimulate insulin secretion by binding to sulfonylurea receptor of ATP-sensitive K+ channels, blocking this channels, thereby triggering events subsequent to reduced K+ influx which results in release of endogenous insulin (from pancreatic beta cells).
By what mechanism do thiazolidinediones exert their blood glucose-lowering effects?
They increase target tissue sensitivity to insulin by activating PPAR-gamma receptor, which regulates transcription of genes encoding proteins involved in carbohydrate and lipid metabolism. They increase glucose uptake in muscle and adipose tissue
They also inhibit hepatic gluconeogenesis and have effects on lipid metabolism and body fat distribution. They reduce both fasting and postprandial hyperglycemia.
Describe the structure of pramlintide and its mechanism for lowering blood glucose.
It is an injectable synthetic analogue of amylin, which contributes to glycemic control by activating high-affinity receptors in both glycemic control and osteogenesis. (does not form aggregates as does human form) Pramlintide suppresses glucagon release, slows gastric emptying, and works in CNS to reduce appetite. It is rapidly absorbed after subcutaneous injection, and has short duration of action.
How does using Dipeptidyl Peptidase (DPP-4) inhibitors reduce blood glucose?
This enzyme normally cleaves GLP-1 (Glucagon-like-peptide 1) and GIP (Glucose-dependent insulinotropic Polypeptide), by removing two N-terminal amino acids. Inhibitors increase concentrations of intact GLP-1 and GIP. GLP-1 is released from endocrine cells in epithelium of bowel in response to food. It augments glucose-stimulated insulin release from pancreatic beta cells, retards gastric emptying, inhibits glucagon secretion, and produces feeling of satiety.
Describe the structure and mechanism of liraglutide.
-Second GLP-1 receptor agonist
-Structurally nearly identical to native GLP-1, with Lys34 to Arg substitution & addition of α-glutamic acid spacer coupled to C16 fatty acyl group
Fatty acid side chain permits binding to albumin & other plasma proteins & accounts for an extended t1/2 permitting once a day administration.
Pharmacodynamic profile mimics GLP-1 and exenatide
What is the benefit of using long-acting insulins such as glargine and detemir?
They provide peakless insulin levels lasting more than 20 hours, helping control basal glucose levels without producing hypoglycemia.
