Pharm2 1 T2DM Agents pt2

Question 1

*This is the oral agent that causes the most Hypoglycemia:

Answer 1

Sulfonylureas

it’s squeezing insulin out of the pancreas

Question 2

How do Sulfonylureas work?

Answer 2

it’s squeezing the insulin out of the pancreas.
increased secretion of pro-insulin, allowing the pancreas to release more insulin into the blood which lowers the glucose level

Question 3

How fast do Sulfonylureas work?

Answer 3

Rapid acting, lowers plasma glucose levels < 24 hrs

Question 4

Besides squeezing insulin out of the pancreas, what else does Sulfonylureas do (3)?

Answer 4

sensitize β-cells to glucose
limit glucose production in the liver
decrease lipolysis and decrease clearance of insulin by the liver

Question 5

__ is a common side effect of Sulfonylureas

Answer 5

Hypoglycemia

Question 6

What often goes wrong with Sulfonylureas?

Answer 6

Many of these drugs are only effective for a few years and then may stop working as the pancreas develops secondary failure or “burns out”
Scenario: an orange (pancreas) is squeezed until there is no juice (insulin) remaining (secondary failure)

Question 7

3 generations of Sulfonylureas
1st gen (1)
2nd gen (2)
3rd gen (3)

Answer 7

Gen 1: Chlorpropamide
Gen 2: Glyburide Glyburide
Gen 3: Glimepiride*

Question 8

___ is almost exclusively the only Sulfonylurea prescribed. What generation Sulfonylurea is it?

Answer 8

Glimepiride (3rd generation)

Question 9

Who would you write Glimipiride (a Sulfonylurea) for their initial therapy instead of Metformin? (2)

Answer 9

someone with a very high glucose. A1C of 12.5. This will lower that glucose burden quicker.
Older patients – for a week. This lowers it down, but not dangerously low, and then you switch to Metformin.

Question 10

Glimipiride

FDA-approved ≥ __ YOA as adjunct to D&E as monotherapy or combination therapy in T2DM

Answer 10

> 18 years old

Question 11

CI of Glimipiride: ___

Cautions of Glimipiride: renal disease or dysfunction; secondary failure may occur with extended therapy

Answer 11

DKA

Question 12

~Glimipiride (Sulfonylureas) have __% efficacy of lowering HbA1C in monotherapy.
In how long?

Answer 12

~2 (0.9 – 2.5) after max dose for a week

Question 13

Thiazolidinediones (TZDs) take how long to work?

Answer 13

Work slowly (~4 weeks)

Question 14

Thiazolidinediones (TZDs) mechanism of action

Answer 14

Binding to peroxisome proliferator-activated receptors (PPARs) receptor molecules inside cell nucleus decreasing insulin resistance, increasing adiponectin levels and ultimately lowering plasma glucose levels

Preserves beta-cell function, reduces advancement of diabetic neuropathy

Question 15

2 examples of TZD’s

Answer 15

Pioglitazone

Rosiglitazone

Question 16

Why aren’t TZD’s (Pioglitazone, Rosiglitazone) prescribed?

Answer 16

Studies had shown increased risk of CVD events &
increased risk of bladder cancer.
THESE STUDIES ARE WRONG.
B/c the patient will google these drugs and think you’re going to kill them. So most avoid this drug, to avoid this problem.

Question 17

2 CI for Pioglitazone

Answer 17

CHF, DKA

Question 18

A take home message on this: when steve nissen did his research on TZDs, it made a new rule. When a drug wants to be approved, there must be 2 additional studies that look at:

Answer 18

psych effects & cardiovascular effects of the drug.

Psych studies can be done within a year, but cv disease can take years to develop..and that will take a long time to get data.

Question 19

*BQ: some women who are perimenopausal get put on Pioglitazone, will all of a sudden no longer be perimenopausal, and come into office with terrible nausea for last week:

Answer 19

resumption of premenopausal ovulation in anovulatory patient may occur and result in unintended pregnancy
They hadn’t had a period in 6 months, thought they were safe…not with this drug.

Question 20

Side effects of Pioglitazone: (think about the CI) (2)

Answer 20

Edema, worsening heart failure, Increased risk of CV events
Increased risk of osteoporotic proximal upper extremity fractures recently discovered (class effect) – most common in women

Question 21

Efficacy of Efficacy in lowering HbA1C in monotherapy

Metformin + Pioglitazone lowers it by how much?

Answer 21

Alone: 1.5 – 1.6%

With Metformin: 3%

Question 22

If patient has HbA1C of 10, you can put them on: …, and it lowers to about 7%, and with diet/exercise it lowers even more to 6.5%

Answer 22

Metformin + Pioglitazone