Page 52 - Medicinal Chemistry Self Assessment

Section 2 Whole Molecule Drug Evaluation

1.12 Chlorpropamide and

Other Sulfonylureas

1.12 Chlorpropamide and Other Sulfonylureas
Shown below are the structures of tolbutamide and chlorpropamide. These drug molecules are used in the treat-

ment of type 2 diabetes mellitus. They stimulate the release of insulin from the pancreatic β-cells by interacting with
Shown below are the structures of tolbutamide and chlorpropamid of ATP)-sensitive potassium channels.
adenosine triphosphate (ATP)-sensitive potassium channels.

1.12 Chlorpropamide and Other Sulfonylureas

Shown below are the structures of tolbutamide and chlorpropamid of ATP)-sensitive potassium channels.

Tolbutamide Chlorpropamide

1. It is not uncommon for patients with type 2 diabetes to be dually diag and require additional occur?
1. It is not uncommon for patients with type 2 diabetes to be dually diagnosed with hypertension and
Chlorpropamide
Tolbutamide

require additional pharmacotherapy. In this scenario, it is possible for drug interactions to occur if the

prescribed combination therapy is not appropriately evaluated. Angiotensin II receptor antagonists,
commonly known as angiotensin II receptor blockers (ARBs), are often used to treat hypertension.
Losartan (shown below) is an ARB, and similar to tolbutamide and chlorpropamide, is highly plasma
1. It is not uncommon for patients with type 2 diabetes to be dually diag and require additional occur?
protein bound. If losartan was selected for use in a patient who is already taking tolbutamide or chlor-
propamide, would you anticipate that a drug interaction could occur?

Losartan

Losartan
2. The normal pK a range for sulfonylureas is 5 to 6. When comparing the pK a values of chlorpropamide.

3. Using your answer from percent of tolbutamide that will be ionized at an intestinal pH of 6.1.

2. The normal pK a range for sulfonylureas is 5 to 6. When comparing the pK a values of chlorpropamide.
4. The mechanism of action of ion functional groups.

3. Using your answer from percent of tolbutamide that will be ionized at an intestinal pH of 6.1.
5. Tolbutamide has a half-life has a significantly longer half-life than tolbutamide.

4. The mechanism of action of ion functional groups.
6. Shown below is a known pathways that are required to produce this metabolite.
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5. Tolbutamide has a half-life has a significantly longer half-life than tolbutamide.

6. Shown below is a known pathways that are required to produce this metabolite.

Metabolite of glyburide

Metabolite of glyburide