EXAM #5: ANTIDIABETIC AGENTS

Question 1

What is the product of alpha cells in the pancreas?

Answer 1

Glucagon

Question 2

What is the product of beta cells in the pancreas?

Answer 2

Insulin and amylin

Question 3

What is the product of delta cells in the pancreas?

Answer 3

Somatostatin

Question 4

What is the product of G cells in the pancreas?

Answer 4

Gastrin

Question 5

What is the product of F cells in the pancreas?

Answer 5

Pancreatic polypeptide

Question 6

What type of hormone is insulin? What are the implications?

Answer 6

• Peptide hormone that can bind EXTRCELLULAR receptors

* Note that from a therapeutic standpoint, oral insulin is not a viable option

Question 7

List the factors that will upregulate insulin release?

Answer 7

Glucose 
Amino acids 
Incretins 
Epi/ B-2 adrenergic 
Vagus

Question 8

List the factors that will downregulate insulin release?

Answer 8

NE/a-2 adrenergic

Amylin

Question 9

Outline the response of the pancreatic beta-cell to glucose.

Answer 9

1) Glucose comes into the cell via the glucose transporter (GLUT-2)
2) Intracellular ATP increases
3) High levels of intracellular ATP cause ATP-sensitive K+ channels to CLOSE
4) Depolarization follows, opening voltage-gated Ca++ channels
5) Ca++ dependent Ca++ release of insulin packaged in secretory vesicles= insulin release

Question 10

What is the major metabolic response to insulin?

Answer 10

Translocation of GLUT-4 transporters from the cytoplasmic compartment to the membrane

*Especially in skeletal muscle and adipose tissue

Question 11

What is the major function of GLUT-4 transporters?

Answer 11

Insulin mediated uptake of glucose

Question 12

Generally, what is the function of insulin action on: 1) fatty acids, 2) glucose, 3) amino acids?

Answer 12

Insulin promotes conversion of smaller molecules to their storage to the storage forms i.e:

1) Fatty acids to TAG
2) Glucose to glycogen
3) Amino acids to protein

Question 13

What metabolic processes are favored in the absence of insulin?

Answer 13

1) Gluconeogenesis

2) Glycogenolysis

Question 14

What is the key difference between Type I and Type II DM?

Answer 14

I= IDDM 
II= NIDDM

Question 15

What is the key pathologic characteristic of Type I DM?

Answer 15

Autoimmune Beta cell destruction leading to absolute insulin deficiency

Question 16

What is the key pathologic characteristic of Type II DM?

Answer 16

Insulin resistance i.e. increased insulin needed for same effect

Question 17

What are the signs/sx of Type I DM?

Answer 17

• Polyuria
• Polydipsia
• Polyphagia

*Remember the 3 P’s of Type I DM

Question 18

What are the signs/sx of Type II DM?

Answer 18

• Infection
• Neuropathy
• Obesity/ metabolic syndrome

Question 19

What is normal fasting blood glucose level?

Answer 19

Less than 100 mg/dL

Question 20

What is a diabetic fasting blood glucose level?

Answer 20

Roughly 140 mg/dL

Question 21

What plasma blood glucose level should one be at an hour or so after a meal?

Answer 21

Less than 200 mg/dL

Question 22

What is the mainstay treatment for Type I DM?

Answer 22

Insulin

Question 23

What is the one route that insulin cannot be administrated?

Answer 23

Oral

*Note that SQ is most common

Question 24

What is the purpose of altering amino acids in the beta chain of insulin?

Answer 24

• Alters the “stickiness” of the insulin
• Will complex with other insulin or not

*Implications for duration of action/onset

Question 25

What has been done to make rapid acting insulin?

Answer 25

Amino acid change so that insulin peptide complexes DO NOT occur

Question 26

What are the examples of rapid-acting insulin?

Answer 26

Insulin lispro Insulin aspart Insulin glulisine

Question 27

What is the onset of rapid acting insulin?

Answer 27

10-30 min

Question 28

What is the duration of action of rapid-acting insulin?

Answer 28

3-5 hours

Question 29

What is an example of short-acting insulin?

Answer 29

Regular insulin *Forms complexes*

Question 30

What is the duration of action for short-acting insulin?

Answer 30

4-12 hours

Question 31

What is an example of intermediate acting insulin?

Answer 31

NPH *Forms protamine-insulin complexes

Question 32

What is the duration of action of intermediate acting insulin?

Answer 32

10-20 hours

Question 33

What are examples of long-acting insulin?

Answer 33

Glargine | Detemir

Question 34

How is insulin formulated to be long-acting?

Answer 34

Forms a precipitate at neutral pH

Question 35

What is the duration of action for long-acting insulin?

Answer 35

12-20 or 22-24 hours

Question 36

What type of insulin is used in an insulin pump vs. SQ injection?

Answer 36

Pump= rapid only SQ= rapid and long-acting

Question 37

How would you manage eating a meal with insulin?

Answer 37

Rapid-short acting

Question 38

How are basal levels of insulin maintained?

Answer 38

Long-acting insulin

Question 39

What is intermediate duration insulin typically used for?

Answer 39

Overnight/ sleeping

Question 40

What is the most common adverse effect of insulin? What are other adverse effects seen with insulin theray?

Answer 40

Hypoglycemia* *Also, injection site reactions--lipohypertrophy or lipoatrophy-- that require changing sites*

Question 41

What are the signs/sx. of hypoglycemia?

Answer 41

SNS: - Tachycardia - Diaphoresis - Tremors - Nausea - Hunger - Confusion - Coma

Question 42

How is hypoglycemia treated?

Answer 42

Glucose or glucagon

Question 43

What is the first line agent to treat DM-II?

Answer 43

Metformin

Question 44

What is the MOA of Metformin?

Answer 44

- Decreased hepatic glucose output - Increased utilization in the peripheral tissue *Not really understood, but NOT dependent on B-cell function*

Question 45

What is the key adverse effect with Metformin?

Answer 45

GI disturbances

Question 46

List the sulfonylureas and meglitinides.

Answer 46

Glimepiride Glipizide Glyburide Repaglinide Nateglinide

Question 47

What is the MOA of the sulfonylureas and meglitinides?

Answer 47

Inhibit ATP-sensitive potassium channel of the Beta-cell resulting in insulin release

Question 48

What adverse effects are seen with the sulfonylureas and meglitinides?

Answer 48

Weight gain | Hypoglycemia

Question 49

What are the Glucosidase inhibitors?

Answer 49

Acarbose | Miglitol

Question 50

What is the MOA of the Glucosidase inhibitors?

Answer 50

Inhibit the brush border glucosidase enzyme the prevent absorption of glucose

Question 51

What adverse effects are seen with Glucosidase inhibitors?

Answer 51

GI disturbances

Question 52

When are Glucosidase inhibitors contraindicated?

Answer 52

Patients with pre-existing GI disorder e.g. Lactose intolerance

Question 53

What are the Thiazolindinediones?

Answer 53

Pioglitazone | Rosiglitazone

Question 54

What is the MOA of the Thiazolindinediones?

Answer 54

Generally, increase the expression of GLUT-4 *Increases peripheral glucose uptake

Question 55

What key adverse effects are associated with Thiazolindinediones?

Answer 55

Cardiovascular | Hepatotoxicity

Question 56

What is the amylinomimetic drug?

Answer 56

Pramlintide

Question 57

What is the MOA of Pramlintide?

Answer 57

- Inhibit glucagon release - Inhibit gastric emptying - Anorectic effect

Question 58

What are the adverse effects of Pramlintide?

Answer 58

- Anorexia - Hypoglycemia - Delayed drug absorption

Question 59

What are the incretins?

Answer 59

Exenatide | Liraglutide

Question 60

What is the MOA of the incretins?

Answer 60

Increased insulin secretion by binding to incretin receptors on beta-cells

Question 61

What adverse effects are associated with the incretins?

Answer 61

Acute pancreatitis

Question 62

What is the normal function of DPP?

Answer 62

Breakdown of incretins *Incretins normally stimulate insulin release

Question 63

What are the DPP inhibitors?

Answer 63

Sitagliptin Saxagliptin Linagliptin

Question 64

What are the adverse effects of DPP inhibitors?

Answer 64

- Acute pancreatitis | - Hemorrhagic/ necrotizing pancreatitis