Diabetes Drugs - Trachte

Question 1

What drug is the only Biguanide that we need to know?

Answer 1

Metformin

Question 2

What is the MOA of Metformin?

Answer 2

Exact mechanism is unknown.

***Inhibits gluconeogenesis => decreases hepatic glucose production

• inhibits hepatic enzyme activities (e.g. Glucose-6-phosphatase which allows the release of glucose from the liver)
• reduces hepatic uptake of gluconeogenic substrates (e.g. lactate)

***Increases insulin sensitivity (increase insulin receptor Tyrosine Kinase activity and stimulation of the GLUT4 transporter to the plasma membrane => takes up more glucose.)

Reduces lipolysis in adipocytes

Reduces glucose absorption from intestine

Question 3

What are the adverse side effects of Metformin?

Answer 3

GI upset - diarrhea

Lactic acidosis = most serious side effect (Circulating lactate is not used as substrate for gluconeogenesis and magnified problem with reduced renal function)

Question 4

What specific drug primarily acts by binding/blocking the SUR1 subunit of the ATP-sensitive potassium channel and closing the channel, resulting in activation of Ca++ channels, thereby increasing intracellular Ca++ levels and depolarizing pancreatic Beta-cells?

Answer 4

Sulfonylurea = Glimepiride

Question 5

What are the adverse side effects of Glimepiride?

Answer 5

Hypoglycemia and weight gain

Question 6

What drug is a GLP-1 analog that inhibits glucagon secretion and stimulates insulin secretion by increasing adenyl cyclase consequently increasing cAMP and increasing intracellular calcium stores?

Answer 6

Exenatide

Question 7

What are the effects (good and bad) of Exenatide?

Answer 7

delays gastric emptying

induces satiety

weight loss

N/V

pancreatitis

Question 8

What drug inhibits glucagon secretion and augments insulin secretion by enhancing the activity of incretins due to preventing the degradation of GLP-1 and GIP?

Answer 8

DPP-IV Inhibitor = Sitagliptin

Question 9

What are the adverse side effects of Sitagliptin?

Answer 9

Well tolerated, not associated with hypoglycemia or weight gain

Question 10

What two drugs are insulin secretagogues that act by binding/blocking ATP-sensitive potassium channels causing depolarization of pancreatic beta-cells?

Answer 10

Meglitinides = Nateglinide and Repaglinide

Question 11

What are the adverse side effects of Nateglinide and Repaglinide?

Answer 11

Hypoglycemia and weight gain

Question 12

What two drugs interfere with hydrolysis of disaccharides and complex carbohydrates to monsaccharides by inhibiting alpha-glucosidases in the intestinal brush border, thereby slowing intestinal digestion/absorption of carbohydrates?

Answer 12

Acarbose and Miglitol

Question 13

What are the side effects of Acarbose and Miglitol?

Answer 13

GI disturbances => osmotic laxative effect

Question 14

What drug delays gastric emptying and inhibits glucagon secretion by binding to amylin receptors inhibiting glucagon synthesis and glucose synthesis in the liver?

Answer 14

Pramlintide

Question 15

What are the effects (good/bad) of Pramlintide?

Answer 15

delayed gastric emptying

increased satiety

nausea

GI upset

Question 16

What two drugs increase insulin sensitivity and glucose uptake/utilization by transcriptionally increasing synthesis and transport of GLUT transporters in muscle, adipose and liver?

Answer 16

PPAR-gamma receptor agonists = Pioglitazone and Rosiglitazone

Question 17

What are the adverse side effects of Pioglitazone and Rosiglitazone?

Answer 17

Weight gain, hepatotoxicity, edema, HF

Question 18

What two classes of drugs are considered “Insulin sensitizers” (e.g. promote insulin-like activities)?

Answer 18

Biguanides = Metformin

Thiazolidinediones/Glitazones/PPAR agonists = Rosiglitazone and Piaglitazone

Question 19

What four drug classes are considered “Insulin secretagogues” (e.g. increase insulin secretion)?

Answer 19

Closing K+ channels: Sulfonylureas (Glimepiride)
and Meglitinides/Glinides (Repaglinide, Nateglinide)

Activation of adenylyl cyclase: GLP-1 analogs (Exenatide) and Dipeptidase IV inhibitors (Sitagliptin)

Question 20

What drugs make you pee out sugar?

Answer 20

Sodium-glucose co-transporter 2 (SGLT-2) inhibitors (“-flozins”) = block reabsorption of glucose in proximal collecting tubule