Insulin Drugs

Question 0

Tolbutamide

Answer 0

Older sulfonylurea drug for type 2 diabetes.

Side Effects: Causes weight gain, hypoglycemia, and can contribute to the depletion of insulin in beta cells.

Question 1

Acarbose and Miglitol

Answer 1

Alpha glucosidase inhibitors: Inhibit or delay carbohydrate absorption in the small intestines. These are saccharides that are competitive inhibitors of enzymes needed to digest carbohydrates. Decrease the rate of carb digestion so smaller rise in glucose after a meal. Can be used for both type 1 and type 2 diabetes.
Side Effects: GI side effects: flatulence, indigestion. (Acarbose, Miglitol).

Question 2

Sulfonylureas and Megliginides

Answer 2

Insulin secretagogues: induce insulin release from pancreatic beta cells. Sulfonylureas or Megliginides bind directly to the ATP-dependentpotassium channels and inactivate them, causing depolarization leading to insulin release from beta cells. ATP not needed.

Question 3

Biguanides

Answer 3

: Most widely prescribed insulin sensitizers and the first line of drug therapy for type II diabetes.
MOA: antihyperglycemic: corrects for elevated glucose output by the liver by decreasing hepatic gluconeogenesis. Decreases absorption of glucose in the intestinal tract. Increases sensitivity to insulin, and increases utilization of glucose by the peripheral tissues. Exact mechanism is unknown. May act as an antagonist to glucagon signaling by inhibiting adenylyl cyclase, thus reducing glucagon-mediated glucose output from the liver. May activate 5AMP-activated protein kinase (AMPK) in liver and muscle, which plays a role in the metabolism of fats and glucose.

Question 4

Troglitazone

Answer 4

Thiazolidinedione: Insulin sensitizer.

Side Effects: withdrawn due to hepatic side effects. Fluid retention leading to risk of cardiac heart failure.

Question 5

Rosiglitazone

Answer 5

Thiazolidinedione: Insulin sensitizer.
Side Effects: Increased risk of bone fractures; increased risk of congestive heart failure and heart attack. Restricted access.

Question 6

Pioglitazone

Answer 6

Thiazolidinedione: Insulin sensitizer. MOA: agonist for PPAR gamma: peroxisome proliferator-activated receptor gamma. Nuclear hormone receptor superfamily. PPAR gamma heterodimerizes with RXR, binds to hormone response elements, regulates transcription of genes. The normal ligand for this receptor is free fatty acids and eicosanoids (leukotrienes and prostaglandins). So its normal activity is to regulate free fatty acids. Modulates transcription of insulin-sensitive genes involved in glucose and lipid metabolism (increases their transcription). Increases insulin sensitivity in the liver and muscle, has a low onset of action (1-2 months for max effect).
Side Effects: increased risk of bone fractures.

Question 7

Insulin sensitizers

Answer 7

Drugs that will make the body make better use of the insulin that is produced and help promote some of the gene transcription events that insulin would normally be promoting. Biguanides and thiazolidinediones.

Question 8

Insulin secretagogues

Answer 8

Increase the secretion of insulin from pancreatic beta cells. Sulfonylureas, meglitinides, GLP-1 agonists, DPP-4 inhibitors.