The remarkable evolution of diabetes treatment is a testament to the power of medicinal chemistry. From modifying the insulin peptide to create rapid- and long-acting analogs, to designing small molecules that precisely target enzymes and receptors, a drug’s chemical structure dictates its therapeutic function. As detailed in the Patient Care 5 curriculum, understanding the medicinal chemistry of these agents allows pharmacists to grasp their mechanisms, predict potential interactions, and provide a higher level of care. This quiz will explore the structure-activity relationships, pharmacophores, and chemical principles underlying the diverse classes of diabetes medications.
1. The core chemical structure required for the activity of sulfonylureas is a(n):
- a. Thiazolidinedione ring
- b. Substituted sulfonyl-urea moiety (R-SO₂NHCONH-R’)
- c. Biguanide structure
- d. Peptide backbone
Answer: b. Substituted sulfonyl-urea moiety (R-SO₂NHCONH-R’)
2. Second-generation sulfonylureas like glipizide are more potent than first-generation agents like tolbutamide primarily because they have:
- a. A smaller molecular weight.
- b. A specific, larger non-polar group on the benzene ring that increases binding affinity.
- c. A lower pKa.
- d. A different mechanism of action.
Answer: b. A specific, larger non-polar group on the benzene ring that increases binding affinity.
3. Metformin is a biguanide that is very hydrophilic. At physiological pH, its structure is:
- a. Uncharged and lipophilic.
- b. Primarily protonated and positively charged.
- c. Negatively charged.
- d. A zwitterion.
Answer: b. Primarily protonated and positively charged.
4. The “-gliptin” drug class (e.g., sitagliptin) works by inhibiting the DPP-4 enzyme. These molecules are structurally designed to:
- a. Mimic the structure of glucose.
- b. Mimic the dipeptide substrate of the DPP-4 enzyme.
- c. Bind to the insulin receptor.
- d. Activate the GLP-1 receptor.
Answer: b. Mimic the dipeptide substrate of the DPP-4 enzyme.
5. SGLT2 inhibitors like canagliflozin are chemically classified as:
- a. Peptides
- b. C-glucoside derivatives
- c. Sulfonylureas
- d. Biguanides
Answer: b. C-glucoside derivatives
6. The “Medicinal Chemistry of Diabetes Medications” is a specific learning module in which course?
- a. PHA5787C Patient Care 5
- b. PHA5104 Sterile Compounding
- c. PHA5703 Pharmacy Law and Ethics
- d. PHA5878C Patient Care 3
Answer: a. PHA5787C Patient Care 5
7. A key medicinal chemistry innovation in developing rapid-acting insulin analogs (e.g., lispro) was:
- a. Adding a fatty acid chain to the molecule.
- b. Switching key amino acid residues to prevent self-association into hexamers.
- c. Increasing the isoelectric point of the molecule.
- d. Making the molecule much larger.
Answer: b. Switching key amino acid residues to prevent self-association into hexamers.
8. Insulin glargine achieves its long duration of action through what chemical modification?
- a. A shift in its isoelectric point, making it less soluble and precipitate at the physiological pH of the subcutaneous tissue.
- b. Attachment of a long fatty acid chain.
- c. Formation of di-hexamers linked by zinc.
- d. PEGylation.
Answer: a. A shift in its isoelectric point, making it less soluble and precipitate at the physiological pH of the subcutaneous tissue.
9. The primary medicinal chemistry goal in designing GLP-1 receptor agonists was to:
- a. Create a small molecule that could be taken orally.
- b. Make the peptide resistant to degradation by the DPP-4 enzyme to prolong its half-life.
- c. Increase the potency of the molecule a thousand-fold.
- d. Remove all side effects.
Answer: b. Make the peptide resistant to degradation by the DPP-4 enzyme to prolong its half-life.
10. Insulin detemir has a fatty acid chain attached to its structure. What is the purpose of this modification?
- a. To make it taste better.
- b. To increase its water solubility.
- c. To promote binding to albumin, which prolongs its duration of action.
- d. To make it a rapid-acting insulin.
Answer: c. To promote binding to albumin, which prolongs its duration of action.
11. The pharmacology of oral and injectable diabetes medications is a specific topic within the Patient Care 5 curriculum.
- a. True
- b. False
Answer: a. True
12. The thiazolidinedione ring is the key pharmacophore for which class of drugs?
- a. Sulfonylureas
- b. DPP-4 inhibitors
- c. SGLT2 inhibitors
- d. TZDs (e.g., pioglitazone)
Answer: d. TZDs (e.g., pioglitazone)
13. TZD drugs like pioglitazone are agonists for which nuclear receptor?
- a. Estrogen Receptor
- b. Androgen Receptor
- c. Peroxisome proliferator-activated receptor gamma (PPARγ)
- d. Thyroid Hormone Receptor
Answer: c. Peroxisome proliferator-activated receptor gamma (PPARγ)
14. Predicting the effects of functional groups on drug properties is a key objective of which foundational course?
- a. PHA5439 Principles of Medicinal Chemistry and Pharmacology I
- b. PHA5161L Professional Practice Skills Lab I
- c. PHA5007 Population Health
- d. PHA5103 Principles of Patient-Centered Care
Answer: a. PHA5439 Principles of Medicinal Chemistry and Pharmacology I
15. What structural feature of SGLT2 inhibitors makes them resistant to breakdown by glucosidases in the gut, allowing for oral administration?
- a. The presence of a sulfur atom.
- b. The C-glycosidic bond, as opposed to an O-glycosidic bond.
- c. Their large size.
- d. Their peptide nature.
Answer: b. The C-glycosidic bond, as opposed to an O-glycosidic bond.
16. The “-gliptin” suffix identifies a drug as a(n):
- a. SGLT2 inhibitor
- b. DPP-4 inhibitor
- c. GLP-1 receptor agonist
- d. TZD
Answer: b. DPP-4 inhibitor
17. The management of diabetes is an active learning session in the Patient Care 5 course.
- a. True
- b. False
Answer: a. True
18. The “-gliflozin” suffix identifies a drug as a(n):
- a. SGLT2 inhibitor
- b. DPP-4 inhibitor
- c. GLP-1 receptor agonist
- d. Sulfonylurea
Answer: a. SGLT2 inhibitor
19. From a medicinal chemistry perspective, insulin and GLP-1 agonists are classified as:
- a. Small molecules
- b. Biologics (peptides/proteins)
- c. Natural products
- d. Alkaloids
Answer: b. Biologics (peptides/proteins)
20. An active learning session on diabetes is part of the Patient Care 5 course.
- a. True
- b. False
Answer: a. True
21. The structure of native human insulin consists of:
- a. A single polypeptide chain.
- b. Two polypeptide chains (A and B) linked by disulfide bonds.
- c. Three polypeptide chains.
- d. A large carbohydrate molecule.
Answer: b. Two polypeptide chains (A and B) linked by disulfide bonds.
22. Which functional group is NOT typically found in the structure of metformin?
- a. Amine groups
- b. A Guanidine-like structure
- c. A large aromatic ring system
- d. Carbon-nitrogen double bonds
Answer: c. A large aromatic ring system
23. The ability of SGLT2 inhibitors to mimic glucose allows them to bind to the SGLT2 transporter. This is an example of a(n):
- a. Covalent interaction
- b. Agonist interaction
- c. Competitive antagonist interaction
- d. Allosteric interaction
Answer: c. Competitive antagonist interaction
24. The medicinal chemistry lectures on diabetes are part of which course module?
- a. Module 1: Diabetes Mellitus
- b. Module 3: Women’s Health
- c. Module 4: Medication Safety
- d. Module 8: Men’s Health
Answer: a. Module 1: Diabetes Mellitus
25. In insulin lispro, the reversal of the proline and lysine amino acids at positions B28 and B29 serves what purpose?
- a. It increases the half-life.
- b. It prevents the formation of dimers and hexamers, leading to rapid absorption.
- c. It makes the insulin more potent.
- d. It changes the mechanism of action.
Answer: b. It prevents the formation of dimers and hexamers, leading to rapid absorption.
26. The “-tide” suffix in drugs like liraglutide and semaglutide indicates that the molecule is a(n):
- a. Steroid
- b. Small molecule inhibitor
- c. Peptide or protein
- d. Alkaloid
Answer: c. Peptide or protein
27. The structure of repaglinide (a meglitinide) lacks the sulfonylurea moiety but acts similarly by:
- a. Binding to the same SUR1 subunit of the K-ATP channel in beta cells.
- b. Inhibiting the SGLT2 transporter.
- c. Activating PPARγ.
- d. Inhibiting DPP-4.
Answer: a. Binding to the same SUR1 subunit of the K-ATP channel in beta cells.
28. An active learning session on the medicinal chemistry of diabetes drugs is part of which course?
- a. PHA5787C Patient Care 5
- b. PHA5163L Professional Skills Lab 3
- c. PHA5781 Patient Care I
- d. PHA5782C Patient Care 2
Answer: a. PHA5787C Patient Care 5
29. The acidic and basic functional groups on a drug molecule determine its pKa, which in turn influences its:
- a. Color
- b. Solubility and degree of ionization at different physiological pH values.
- c. Molecular weight
- d. Potency
Answer: b. Solubility and degree of ionization at different physiological pH values.
30. The “Medicinal Chemistry of Diabetes Medications – Part 1” is a lecture in the Patient Care 5 curriculum.
- a. True
- b. False
Answer: a. True
31. The primary structural difference between metformin and other oral antidiabetic agents is that metformin is:
- a. Highly lipophilic.
- b. A large peptide.
- c. Non-aromatic and highly polar.
- d. A prodrug.
Answer: c. Non-aromatic and highly polar.
32. The “pharmacophore” for the TZD class is the:
- a. Sulfonylurea group
- b. Biguanide group
- c. Thiazolidinedione ring system
- d. Amino acid backbone
Answer: c. Thiazolidinedione ring system
33. The development of insulin analogs is a classic example of applying medicinal chemistry to:
- a. Create a completely new drug class.
- b. Modify the pharmacokinetic profile of a known biologic.
- c. Reduce the cost of manufacturing.
- d. Eliminate all side effects.
Answer: b. Modify the pharmacokinetic profile of a known biologic.
34. Which of the following is a key feature of the chemical interaction between a sulfonylurea and its receptor (the SUR1 subunit)?
- a. Covalent bonding
- b. Hydrogen bonding and hydrophobic interactions
- c. Metal chelation
- d. Azo bond cleavage
Answer: b. Hydrogen bonding and hydrophobic interactions
35. A key medicinal chemistry principle is that a drug’s activity is highly dependent on its:
- a. Packaging
- b. Three-dimensional shape and ability to fit into a binding site.
- c. Marketing budget
- d. Name
Answer: b. Three-dimensional shape and ability to fit into a binding site.
36. The stability of a peptide drug like a GLP-1 agonist is a major challenge in its:
- a. Mechanism of action
- b. Patient counseling
- c. Formulation and storage
- d. Side effect profile
Answer: c. Formulation and storage
37. Alpha-glucosidase inhibitors like acarbose are pseudo-carbohydrates that work by:
- a. Competitively inhibiting the enzymes that break down complex carbohydrates in the gut.
- b. Stimulating insulin release.
- c. Blocking glucose reabsorption in the kidney.
- d. Increasing insulin sensitivity.
Answer: a. Competitively inhibiting the enzymes that break down complex carbohydrates in the gut.
38. The “Medicinal Chemistry of Diabetes Medications – Part 2” is a lecture in the Patient Care 5 curriculum.
- a. True
- b. False
Answer: a. True
39. The chemical modifications made to create long-acting insulins all serve to do what at the subcutaneous injection site?
- a. Speed up absorption.
- b. Slow down absorption.
- c. Prevent degradation.
- d. Cause a local anesthetic effect.
Answer: b. Slow down absorption.
40. An active learning session covering the medicinal chemistry of diabetes medications is part of which course module?
- a. Module 1: Diabetes Mellitus
- b. Module 3: Women’s Health
- c. Module 4: Medication Safety
- d. Module 8: Men’s Health
Answer: a. Module 1: Diabetes Mellitus
41. The “-gli-” or “-gly-” infix in drugs like glipizide and glyburide is a hint that they are:
- a. Related to glucose-lowering.
- b. GLP-1 agonists.
- c. SGLT2 inhibitors.
- d. Insulins.
Answer: a. Related to glucose-lowering.
42. From a medicinal chemistry standpoint, a major difference between insulin and all oral antidiabetic agents is:
- a. Insulin is a protein, while the oral agents are small molecules.
- b. Insulin has no side effects.
- c. The oral agents are all prodrugs.
- d. Insulin does not have a defined chemical structure.
Answer: a. Insulin is a protein, while the oral agents are small molecules.
43. The design of a competitive inhibitor, like an SGLT2 inhibitor, involves creating a molecule that:
- a. Binds irreversibly to the target.
- b. Resembles the natural substrate enough to bind to the active site but does not undergo the reaction.
- c. Binds to an allosteric site on the target.
- d. Activates the target.
Answer: b. Resembles the natural substrate enough to bind to the active site but does not undergo the reaction.
44. Which functional group is NOT found in the structure of pioglitazone?
- a. A thiazolidinedione ring
- b. An ether linkage
- c. A peptide bond
- d. A pyridine ring
Answer: c. A peptide bond
45. What is the role of zinc in formulations of regular and NPH insulin?
- a. It acts as a preservative.
- b. It promotes the formation of insulin hexamers, which stabilizes the protein and affects the absorption profile.
- c. It improves the taste.
- d. It is the active ingredient.
Answer: b. It promotes the formation of insulin hexamers, which stabilizes the protein and affects the absorption profile.
46. The structural basis for metformin’s inability to be significantly metabolized is:
- a. It is too large.
- b. It is a peptide.
- c. Its polar, non-lipophilic nature makes it a poor substrate for CYP450 enzymes.
- d. It is too lipophilic.
Answer: c. Its polar, non-lipophilic nature makes it a poor substrate for CYP450 enzymes.
47. Understanding how prodrugs work is a key objective in the Medicinal Chemistry curriculum.
- a. True
- b. False
Answer: a. True
48. An active learning session on diabetes is part of which course?
- a. PHA5787C Patient Care 5
- b. PHA5163L Professional Skills Lab 3
- c. PHA5781 Patient Care I
- d. PHA5782C Patient Care 2
Answer: a. PHA5787C Patient Care 5
49. The development of orally administered semaglutide required significant medicinal chemistry and formulation work, including co-formulation with an absorption enhancer called:
- a. SNAC (salcaprozate sodium)
- b. Polyethylene glycol
- c. Talc
- d. Lactose
Answer: a. SNAC (salcaprozate sodium)
50. The ultimate reason to study the medicinal chemistry of diabetes drugs is to:
- a. Be able to synthesize them.
- b. Understand the relationship between molecular structure and pharmacological action, leading to more rational drug use and patient counseling.
- c. Pass the medicinal chemistry exam.
- d. Appreciate the beauty of organic chemistry.
Answer: b. Understand the relationship between molecular structure and pharmacological action, leading to more rational drug use and patient counseling.