Pharm2 1 T2DM Agents pt2 Flashcards
*This is the oral agent that causes the most Hypoglycemia:
Sulfonylureas
it’s squeezing insulin out of the pancreas
How do Sulfonylureas work?
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
How fast do Sulfonylureas work?
Rapid acting, lowers plasma glucose levels < 24 hrs
Besides squeezing insulin out of the pancreas, what else does Sulfonylureas do (3)?
sensitize β-cells to glucose
limit glucose production in the liver
decrease lipolysis and decrease clearance of insulin by the liver
__ is a common side effect of Sulfonylureas
Hypoglycemia
What often goes wrong with Sulfonylureas?
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)
3 generations of Sulfonylureas 1st gen (1) 2nd gen (2) 3rd gen (3)
Gen 1: Chlorpropamide
Gen 2: Glyburide Glyburide
Gen 3: Glimepiride*
___ is almost exclusively the only Sulfonylurea prescribed. What generation Sulfonylurea is it?
Glimepiride (3rd generation)
Who would you write Glimipiride (a Sulfonylurea) for their initial therapy instead of Metformin? (2)
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.
Glimipiride
FDA-approved ≥ __ YOA as adjunct to D&E as monotherapy or combination therapy in T2DM
> 18 years old
CI of Glimipiride: ___
Cautions of Glimipiride: renal disease or dysfunction; secondary failure may occur with extended therapy
DKA
~Glimipiride (Sulfonylureas) have __% efficacy of lowering HbA1C in monotherapy.
In how long?
~2 (0.9 – 2.5) after max dose for a week
Thiazolidinediones (TZDs) take how long to work?
Work slowly (~4 weeks)
Thiazolidinediones (TZDs) mechanism of action
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
2 examples of TZD’s
Pioglitazone
Rosiglitazone
Why aren’t TZD’s (Pioglitazone, Rosiglitazone) prescribed?
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.
2 CI for Pioglitazone
CHF, DKA
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:
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.
*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:
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.
Side effects of Pioglitazone: (think about the CI) (2)
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
Efficacy of Efficacy in lowering HbA1C in monotherapy
Metformin + Pioglitazone lowers it by how much?
Alone: 1.5 – 1.6%
With Metformin: 3%
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%
Metformin + Pioglitazone
