Endocrine Med Chem Diabetic Agents Flashcards
All of the following are functions of GLP-1 in the body EXCEPT:
A. Increase insulin secretion
B. Decrease glucagon release
C. Shortens gastric emptying time
D. Delays gastric emptying time
E. Decreases food intake
C. Shortens gastric emptying time
GLP-1 in the body acts in three locations: Stomach, Pancreas and CNS
Stomach: Delays gastric emptying
Pancreas: Increases insulin secretion, Decreases glucagon release
CNS: Reduces food intake
What enzyme is responsible for deactivating GLP-1 in the body?
A. Esterase
B. Hydroxylase
C. SGLT-2
D. DPP-IV
D. DPP-IV
Which of the folowing medications is a GLP-1 Receptor Agonist? (Select All)
A. Exenatide (Byetta)
B. Liraglutide (Victoza)
C. Pioglitazone (Actos)
D. Lixisenatide (Adlyxin)
E. Dulaglutide (Trulicity)
A, B, D, E
GLP-1 agonists end in “tide”
Exenatide is available in two forms. The extended release form is known as ____ and is dosed ____.
A. Byetta, Weekly
B. Bydureon, Weekly
C. Byetta, Twice Daily
D. Bydureon, Twice Daily
B. Bydureon, Weekly
What structural difference is seen in Bydureon that gives it a longer DOA than Byetta?
A. Fatty-acid side chains
B. Ketone functionalities
C. Microspheres
E. Amino acids
C. Microspheres
Based on the Homology, which of the following GLP-1 Receptor Agonists is the MOST similar to the native GLP-1 produced in our gut?
A. Exenatide, Homology 53%
B. Liraglutide, Homology 96%
B. Liraglutide
Homology is the measure of how similar the GLP-1 Agonist is to the native GLP-1 produced in the gut
When comparing the structures of Exenatide (Byetta) and Liraglutide (Victoza), what is the purpose of the blue structure in Liraglutide?
A. Increases first-pass metabolism of the Liraglutide in order to reduce toxicity
B. Increases hydrophilicity of the molecule
C. Increases half-life of the drug
D. Decreases half-life of the drug
C. Increases half-life of the drug
The blue group is a large C16-fatty-acid chain that gives it a longer half-life in the body.
Due to this chain it gives Liraglutide a half-life of 13 hours and once-daily administration in comparison to exenatide with twice daily administration.
Which of the following is a structural modification of the GLP-1 receptor agonist Albiglutide (Tanzeum)?
A. Contains Microspheres to increase dosing to once weekly
B. Contains a dimer of GLP-1 fused to albumin (fusion protein) to increase dosing to once weekly
C. Contains little-to-no structural modification in order to make it a rapid acting agent with twice daily dosing
D. Contains a large C16 Fatty-acid chain that increases it’s half-life of elimination
B. Contains a dimer of GLP-1 fused to albumin (fusion protein) to increase dosing to once weekly
The answer A is describing the medication Bydureon, the answer C is describing the medication Byetta and the answer D is describing the medication Liraglutide
Which of the following are components that make up the GLP-1 Agonist Dulaglutide (Trulicity)? (Select All)
A. GLP-1 Analog
B. C16 fatty-acid chain
C. Linker
D. Sulfonyl group
E. Modified IgG4 Fc Domain
A. GLP-1 Analog
C. Linker
D. Modifed IgG4 Fc Domain
This was just something on his slides
The GLP-1 Agonist Lixisenatide (Adlyxin) contains which structrual modification?
A. Six Prolines added
B. Six Lysine residues added
C. Six Guanidine cores added
D. Six GLP-1 molecules (hexamer) added
B. Six Lysine residues added
Li= Lysine
Xis=Six
Lixisenatide
Which of the folliwing medications is an Amylin Agonist?
A. Pioglitazone
B. Liraglutide
C. Exenatide
D. Sitagliptin
E. Pramlintide
E. Pramlintide
Amylin=Pramlintide
(Short Answer) What is the function of Amylin in the body and why is it not used as a drug itself?
Amylin (37-amino acid peptide)
Suppresses glucagon secretion
Decreases food intake (appetite center in brain)
It is not used as a drug by itself because it aggregates and as a result it is insoluble in solution
What is the structural difference in the Amylin agonist Pramlintide and the natural peptide Amylin
A. Substitution of Alanine group in Pramlintide
B. Substitution of Proline group in Pramlintide
C. Substitution of Lysine group in Pramlintide
D. Substitution of Aspartate group in Pramlintide
B. Substitution of Proline group in Pramlintide
Pr=Proline
Pramlintide
What is the purpose of substituting the Proline group in the Amylin Agonist Pramlintide? (select all)
A. Increases water solubility
B. Increases self-aggregation
C. Decreases self-aggregation
D. Decreases water solubility
A. Increases water solubility
C. Decreases self-aggregation
Remember the initial problem with giving amylin itself as a medication treat is that it would self-aggregate and decrease solubility as a result. By adding the proline group to the structure and creating Pramlintide it stops aggregation and increases water solubility.
Regarding the core structure of the sulfonylurea, the blue circled group is the ___ and the red circled group is the ___.
A. Sulfone, Urea
B. Urea, Sulfone
A. Sulfone, Urea
What is the MOA of sulfonylurea medications?
A. Binds to sulfonyl urea receptors (SUR) on pancreatic Beta cells to increase insulin production
B. Inhibits the SGLT-2 transporter to reduce the reabsorption of glucose
C. Stimulates GLP-1 receptors
D. Decreases hepatic glucose production and increases insulin sensitivity
A. Binds to sulfonyl urea receptors (SUR) on pancreatic Beta cells to increase insulin production (secretogogue)
Can also bind to SUR receptors in cardiac and smooth muscle which is why some Sulfonylureas can cause cardiovascular side effects
Which of the following SARs is true regarding structural modifications at the R1 and R2 groups between First and Second generation sulfonylureas? (Select All)
A. First Gen: R1 has small substitution and R2 has only cyclic aliphatic groups
B. First Gen: R1 has bulky substitution and R2 has only cyclic aliphatic groups
C. Second Gen: R1 has bulky substitution and R2 has only cyclic aliphatic groups
D. First Gen: R1 has small substitution and R2 has either a cyclic or a non-cyclic aliphatic group
C. Second Gen: R1 has bulky substitution and R2 has only cyclic aliphatic groups
D. First Gen: R1 has small substitution and R2 has either a cyclic or a non-cyclic aliphatic group
Based on the sulfonylurea structures provided it can be concluded that they are all ____
A. First Generation
B. Second Generation
A. First generation
In the picture provided here you will see the main core structure of a sulfonylurea boxed in Blue and the R1 and R2 groups boxed in Red
First generation:
- R1=small sub
- R2= Cyclic OR non cyclic
Based on the sulfonylurea structures provided it can be concluded that they are all ____
A. First Generation
B. Second Generation
B. Second Generation
The following picture has the sulfonylurea core structure boxed in blue and the R1 and R2 groups boxed in red. Do not include the core structure in the R1 and R2 group otherwise you may end up mistaking a First Gen with a Second Gen
Second Generation:
- R1: Bulky substitution
- R2: Cyclic ONLY
Regarding the differences between the First and Second Generation Sulfonylureas: which of the following statments is False?
A. First generation sulfonylureas have longer DOA than second generation
B. Second generation sulfonylureas have less side effects than first generation
C. Second generation sulfonylureas are more potent than first generation
D. Second generation sulfonylureas have a longer DOA than first generation
A. First generation sulfonylureas have longer DOA than second generation
This is generally false for most of the first generation medications EXCEPT for Chorpropamide. This first generation sulfonylurea has a longer DOA due to undergoing slow oxidation and as a result it lasts longer in the body
When comparing the structure of sulfonylureas to non-sulfonylureas (Meglitinides), the sulfonylurea group was removed and replaced with a(n)____.
A. Aldehyde
B. Amide
C. Ketone
D. Guanidine
E. Carboxylic Acid
E. Carboxylic Acid
In the picture there is a second generation sulfonylurea (glyburide) being compared to a non-sulfonylurea (Meglitinide) and you can see that the sulfonylurea group is missing but the rest of the structure is similar (red) between the two groups.
Metformin is known as a Biguanide. Judging by the name, what functional groups do you think metformin contains?
A. Two Sulfer groups
B. Two Amide groups
C. Two Guanidine groups
D. Two Urea groups
C. Two Guanidine groups
Bi= Two
Guanide= Guanidine
Biguanide
Also remember that metformin is VERY basic due to the large amount of nitrogen groups in the guanidine structures.
Answer the following question provided
C. Metformin
What functional groups do Thiazolidinediones contain? (Select All)
A. Sulfer
B. Nitrogen
C. Aldehyde
D. Fluoro
E. Ketone
A, B, E
Thi- Sulfer (thiol)
Azo- Nitrogen
Dione= Two ketones
Thiazolidinedione
Answer the following question provided:
C. Linagliptin (Tradjenta)
This is because Linagliptin is primarily excreted in the feces NOT in the urine. Here are the elimination percentages (don’t need to know them but know which are eliminated renally). Refer to slides 47-50 for unique structures
Sitagliptin: 87% urine
Saxagliptin: 75% urine
Linagliptin: 80% Feces, 5% urine
Alogliptin: 76% Urine
What is the MOA of a-Glucosidase Inhibitors?
A. Prevent the hydrolysis of carbohydrates in the GI tract, limiting their absorption
B. Prolongs the lifespan of GLP-1 in the body in order to increase insulin secretion
C. Decreases glucagon secretion by inhibiting the activity pancreatic cells
D. Increases insulin secretion by directly stimulating pancreatic beta cells
A. Prevent the hydrolysis of carbohydrates in the GI tract, limiting their absorption
By preventing the hydrolysis of carbohydrates it will be possible to prevent a large portion of their absorption into systemic circulation, decreasing glucose levels in the blood.
Specifically they are preventing the conversion of disaccharides to monosaccharides
What are the possible side effects of SGLT-2 inhibitors? (select all)
A. Hyperkalemia
B. Hypokalemia
C. Diabetic ketoacidosis
D. Polyuria
E. Genitourinary infection
A. Hyperkalemia
C. Diabetic ketoacidosis
D. Polyuria
E. Genitourinary infection
The following picture shows how. If you can’t absorb glucose and sodium then potassium cannot be countertransported into the kidneys for elimination from the body (hyperkalemia). If you lose glucose in the body then the body has to rely on lipolysis for energy production, this creates ketone bodies and leads to diabetic ketoacidosis.
The following picture depicts the structure of insulin. The A and B chains of insulin are linked at the ___ amino acids by ___ bonds.
A. Cysteine, Disulfide
B. Cysteine, Ionic
C. Cysteine, Hydrogen
D. Cysteine, Hydrophobic
A. Cysteine, Disulfide
The Rapid-Acting Lispro (Humalog) was created by altering the B28 Proline to B28 ___ and the B29 Lysine to B29 ___ on regular insulin.
A. Proline, Lysine
B. Lysine, Proline
C. Aspartate, Proline
D. Proline, Aspartate
B. Lysine, Proline
The Rapid-Acting Aspart (NovoLog) was created by altering the B28 Proline to B28 ___ on regular insulin
A. Asparagine
B. Glycine
C. Cysteine
D. Aspartate
D. Aspartate
The Rapid-Acting Glulisine (Apidra) was created by altering the B3 Asparginine to B3 ___ and B29 Lysine to B29___ in regular insulin.
A. Lysine, Glutamate
B. Lysine, Glycine
C. Glycine, Lysine
D. Glutamate, Lysine
A. Lysine, Glutamate
The Long-Acting Insulin Glargine (Lantus) was created by changing the A21 Aspargine to A21 ___ and adding the B31 and B32 ___.
A. Glutamate, Arginine
B. Glutamate, Asparagine
C. Glycine, Arginine
D. Glycine, Asparagine
C. Glycine, Arginine
The Long-Acting Insulin Detemir was created by adding a C14 Fatty-Acid known as ___ to B29 Lysine.
A. Glycolytic acid
B. Melatoic acid
C. Delatoic acid
D. Myristic acid
D. Myristic acid
One way to remember this is:
DeteMIR=Myristic acid
This long fatty acid chain increases the drugs duration of action because it keeps it bound to plasma albumin
