Drugs for Diabetes

Question 1

Blood Glucose Levels

Answer 1

• Physiology of blood glucose levels depends on times after eating
• Also depends on insulin and glucagon
• Glucose levels increase postprandially
• Levels drops during times of fasting

Question 2

High Glucose Levels

Answer 2

• Stimulates insulin

- Suppresses glucagon secretion

Question 3

Low Glucose Levels

Answer 3

-Stimulates glucagon secretion

Question 4

Postprandial Insulin Secretion

Answer 4

• Insulin secretion from pancreatic B-cells
• Requires glucose uptake and metabolism (glycolysis) that generates ATP
• Incretin hormones enhance glucose-dependent insulin secretion by generating cAMP from ATP

Question 5

Postprandial Insulin Secretion/Glucagon Suppression

Answer 5

• Incretin hormones are secreted by intestinal cells during a meal
• Enhance glucose-dependent insulin secretion and glucose-dependent glucagon suppression

Question 6

Incretins

Answer 6

• Glucagon-like peptide-1 (GLP-1)

- Gastric inhibitory peptide (GIP)

Question 7

Insulin + Glucose Levels

Answer 7

• Stimulates the exocytosis of GLUT4 to cell membrane
• Allows for uptake of glucose into adipose and striated muscle (skeletal and cardiac)
• Reduces blood glucose levels

Question 8

Fasting Glucagon Secretion/Action

Answer 8

• Low blood glucose stimulates glucagon

- Glucagon maintains fasting blood glucose by stimulating glucose synthesis (gluconeogenesis) and glycogen break down

Question 9

Diabetes Drug Mechanisms

Answer 9

1. Replacing insulin
2. Stimulating insulin secretion
3. Mimicking incretin action
4. Stimulating insulin action
5. Blocking glucose reabsorption from urine

Question 10

Insulin Mimetics

Answer 10

Regulates either…
1. Postprandial blood glucose levels
OR
2. Fasting blood glucose levels

Question 11

Insulin Mimetics Action

Answer 11

• Mimics endogenous insulin with only the rate of action being drug dependent
• Site of action: adipose, striated muscle, liver

Question 12

Insulin Mimetics MoA

Answer 12

• Stimulate exocytosis of GLUT4 transporters
• Stimulate glycogen synthesis
• Stimulate glucose metabolism to ATP and fatty acids

Question 13

Insulin Mimetics Pharmacological Effect

Answer 13

• Fast-acting to reduce postprandial glucose
• Slow-acting to reduce fasting glucose
• Intermediate acting to reduce postprandial and fasting-glucose (NPH)

Question 14

Insulin Mimetic SE

Answer 14

• Hypoglycemia

- Weight gain

Question 15

Glucose-Independent Insulin Secretagogues

Answer 15

• Sulfonylureas (G…ide)

- Meglitinides (…glinide)

Question 16

Sulfonylurea

Answer 16

• Glypizide
• Glimepiride
• Glyburide

Question 17

Meglitinide

Answer 17

• Repaglinide

- Nateglinide

Question 18

Sulfonylurea/Meglitinide

Answer 18

• Hypoglycemia
• Weight gain
• Nausea

Question 19

Incretin Mimetics/Glucose-dependent insulin secretion

Answer 19

• GLP-1 analogs (…tide) - convert ATP to cAMP which enhances insulin exocytosis
• DPP4 Inhibitors (….gliptin) - increase GLP-1 half life

Question 20

Glucose-Dependent Insulin Secretion MoA

Answer 20

• Requires glucose uptake

- Metabolism that generates ATP

Question 21

GLP-1 Analogs

Answer 21

• Exenatide
• Liraglutide
• Dulaglutide

Question 22

DPP4 Inhibitors

Answer 22

• Sitagliptin

- Linagliptin

Question 23

GLP-1 Analog Additional Pharmacological Benefits

Answer 23

• Increase satiety (feeling full)
• Decrease appetite (feeling hungry)
• Reduce gluconeogenesis
• Cardioprotective: reduces SBP, increase CO

Question 24

GLP-1 Analogs SE

Answer 24

• Weight loss
• Nausea
• Vomiting
• Diarrhea

Question 25

DPP4-I SE

Answer 25

- Weight neutral | - Fewer GI SE

Question 26

Insulin Sensitizer - Metformin

Answer 26

- Activates AMP kinase (AMPK) which increases GLUT4 expression - Expression of genes associated with gluconeogenesis

Question 27

Insulin Sensitizer - Thiazolidinedione (TZD)

Answer 27

- Binds to PPARy receptor and increases expression of GLUT4 transporters - More of these are exocytosed to membrane when stimulated by insulin

Question 28

TZD

Answer 28

(...glitazone) - Rosiglitazone - Pioglitazone

Question 29

Metformin SE

Answer 29

-GI discomfort (>10%)

Question 30

TZD SE

Answer 30

- Weight gain - Edema - may result from renal sodium retention, 5-10% - Fatigue

Question 31

SGLT2-I

Answer 31

- Prevent reabsorption of glucose filtered into the urine - Increases glucose excretion in urine - MoA independent on insulin levels

Question 32

SGLT2-I

Answer 32

- (....gliflozin) - Canagliflozin - Empagliflozin - Dapagliflozin - Ertugliflozin

Question 33

SGLT2-I Additional Pharmacological Benefits

Answer 33

- Antihypertensive - osmotic diuretic action, inhibit RAAS - Renoprotective - slow progression of renal disease - Weight loss - Minimal risk of hypoglycemia

Question 34

SGLT2-I SE

Answer 34

- Orthostatic hypotension - volume depletion - Polyuria - Usinary tract infection - Yeast infections - more in women **All result form diuretic effects and increased glucose in urine**

Question 35

Alpha-Glucosidase Inhibitor

Answer 35

- Acarbose - Miglitol - MoA: Inhibit α-glucosidase in small intestine and slow rate of glucose absorption - Diabetic Use: Oral drug used to slow increase in postprandial glucose levels

Question 36

Amylin Analog

Answer 36

- Pramlintide - MoA: inhibits glucagon secretion, slows gastric emptying, and increases satiety - Diabetic Use: Adjunctive injection therapy to insulin