Week 1 - Pharmacological Management of DM

Question 1

How can diabetes mellitus be diagnosed (lab criteria)?

Answer 1

Any one of the following criteria can diagnose diabetes:
FBG > 7
A1c > 6.5
OGTT 2hr > 11
Random PG >11

Question 2

What are microvascular complications of DM?

Answer 2

Retinopathy
Nephropathy
Neuropathy

Question 3

What are macrovascular complications of DM?

Answer 3

Stroke, HTN, Peripheral vascular disease, foot problems

Question 4

What is the ideal HbA1c level?

Answer 4

4 - 6 %

Question 5

What is the best way for measuring obesity? Why?

Answer 5

Waist circumference - better than BMI at correlating to cardiac outcomes.

Question 6

What is the best method for preventing diabetes?

Answer 6

Exercise!

Question 7

Briefly, how should diabetes be monitored?

Answer 7

HbA1c every 3 months

SMBG (slef-monitoring blood glc)

Question 8

What are some oral hypoglycemic agents?

Answer 8

• Insulin
• Insulin secretagogues (ex. sulfonylureas)
• Biguanides
• Alpha-glucosidase inhibitors
• thiazolidinediones
• Incretins
• SGLT2 Inhibitors

Question 9

What is a class within insulin secreteagogues?
What is the mechanism of insulin secretagogue action?

Answer 9

Sulfonylureas

• binds to receptor on beta cell
• causes K+ channel to close
• get more depolarization and action potential firing
• Ca++ enters cell
• Insulin granules get secreted

Question 10

By approximately how much do sulfonylureas reduce the HbA1c?

Answer 10

1 - 2 %

Question 11

How are sulfonylureas metabolized/excreted?

Answer 11

Metabolized in liver

Excreted via kidneys (60-70%)

Question 12

What are some side effects of sulfonylureas?

Answer 12

weight gain, hypoglycemia

Question 13

Name some sulfonylureas.

Which is associated with less hypoglycemia?

Answer 13

Glyburide
Gliclazide
Glimepiride (a/w less hypoglycemia)

Question 14

What is the mechanism of action of Meglitinides?

Answer 14

• Bind K+ channel on beta cells

- stimulate APs and insulin release

Question 15

How are meglitinides metabolized/excreted?

Answer 15

metabolized in liver; excreted in feces (90%)

Question 16

Name some examples of Meglitinides.

Answer 16

Repaglinide

Nateglinide

Question 17

What is the mechanism of action of Alpha-Glucosidase Inhibitors?

Answer 17

• competitively inhibits pancreatic alpha-amylase & intestinal membrane-bound alpha-glucosidase.
• decreases conversion of CHO to monosaccharides
• (ie. delays carb metabolism and mellows the glc spike)

Question 18

By approximately how much do alpha-glucosidase inhibitors lower the HbA1c?

Answer 18

0.4 - 1 %

Question 19

Give an example of an alpha-glucosidase inhibitor.

Answer 19

Acarbose

Question 20

What are the side effects of alpha-glucosidase inhibitors?

Answer 20

GI upset; hypoglycemia;

does NOT affect weight

Question 21

What is the mechanism by which Biguanides act?

Answer 21

• reduce insulin sensitivity
• reduce hepatic gluconeogenesis
• increase insulin-stimulated glc transport at muscle
• decrease FA oxidation

Question 22

What’s the difference between sulfonylureas and meglitinides?

Answer 22

Meglitinides have a weaker binding affinity

Question 23

By approximately how much do biguanides reduce the HbA1c?

Answer 23

1-2%

Question 24

What are the side effects of biguanides?

Answer 24

• diarrhea, N/V, bloating, flatulence, metallic taste

- does NOT affect weight

Question 25

How do Thiazolidinediones work?

- what is the mecahnism in different organs?

Answer 25

Increase responsiveness and efficiency of beta cells.

• Liver: decrease insulin resistance & decrease glc/fat production
• Muscle/Fat: decrease insulin resistance
• Pancreas: decrease demand for insulin secretion & increase insulin content in beta cell

Question 26

What are some side effects of Thiazoladinediones?

Answer 26

Weight gain, fluid retention, CHF

Question 27

What are some examples of thiazolidinediones?

Answer 27

Rosiglitazone

Pioglitazone

Question 28

Where is GLP secreted and was are its actions?

Answer 28

GLP is secreted from L cells in the intestine & colon.
- stimulates insulin/reduces glucagon secretion
- slows gastric emptying & reduces food intake
Long term: increases beta cell mass & function

Question 29

What is DPP-4?

How is this used as a drug target?

Answer 29

DPP-4 is a protein that inactivates GLP-1.

DPP-4 inhibitors increase endogenous GLP and lead to glucagon-like action.

Question 30

What is the mechanism of action of SGLT-2 inhibitor?

Answer 30

Blocks the Na+/Glc transporter in the proximal tubule of the kidney to prevent glc reabsorption, thus lowering blood glucose.

Question 31

What are some side effects of SGLT-2 inhibitors?

Answer 31

• increased risk of urogenital mycotic infections
• increased LDL
• weight loss

Question 32

What are prototypical SGLT-2 Inhibitors?

Answer 32

“-gliflozins”

Dapaglifozin, Canaglifozin, Empaglifozen

Question 33

What are some types of short-acting insulin?

Answer 33

Insulin Regular

lispro, glulisine, aspart

Question 34

What are some types of intermediate/long-acting insulin?

Answer 34

NPH, glargine, detemir

Question 35

What are some major issues with insulin?

Answer 35

• hypoglycemia
• weight gain
• variable kinetics/compatibility
• need to adjust with renal dysfunction

Question 36

What drug should treatment of Type 2 DM start with?

Answer 36

Metformin

Question 37

What can be done to monitor for/prevent macrovascular disease?

Answer 37

• Treat dyslipidemia
• Monitor for CAD and CVD (statin therapy?)
  May use anti-platelet tx for secondary prevention

Question 38

What can be done to monitor for/prevent microvascular disease?

Answer 38

• Annual eye exams
• Monitor for proteinuria
• Regular foot exams
• Sexual hx for ED
• Evaluate gastric emptying