Page 164 - Medicinal Chemistry Self Assessment

Section 4 Whole Molecule Drug Evaluation

Answers

2.12 Chlorpropamide and

Other Sulfonylureas

2.12 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 potassium channels.
adenosine triphosphate (ATP)-sensitive potassium channels.

2.12 Chlorpropamide and Other Sulfonylureas

Shown below are the structures of tolbutamide potassium channels.

Tolbutamide Chlorpropamide

1. It is not uncommon for patients with type 2 diabetes ate that a drug interaction could occur?
1. It is not uncommon for patients with type 2 diabetes to be dually diagnosed with hypertension and
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,
Tolbutamide
Chlorpropamide

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
protein bound. If losartan was selected for use in a patient who is already taking tolbutamide or chlor-
1. It is not uncommon for patients with type 2 diabetes ate that a drug interaction could occur?
propamide, would you anticipate that a drug interaction could occur?

Losartan

Answer Losartan
Plasma protein binding interactions (also known as that a drug interaction could occur.

Answer Sulfonylurea Sulfonylurea
Answer
Plasma protein binding interactions (also known as plasma protein displacement interactions) occur due
to the nonspecific nature of the plasma proteins that bind and transport drug molecules. There are two
Plasma protein binding interactions (also known as that a drug interaction could occur.
key concepts to consider when evaluating the probability of a plasma protein binding interaction. First,

these types of interactions are therapeutically important only when the drug molecules are highly plasma
protein bound (i.e., over 90%). Second, acidic drugs primarily bind to albumin, whereas basic drugs
Sulfonylurea
Sulfonylurea
primarily bind to α -glycoprotein. The information provided in the question indicates that all of these
Tolbutamide
1
Chlorpropamide
compounds are highly plasma protein bound; therefore, we need to evaluate the acid/base nature of
153
Chlorpropamide Tolbutamide
Acidic protons
are circled
Tetrazole
Losartan
Acidic protons
are circled

Tetrazole

Losartan