Diabetic Agents

Question 1

Describe the mode of action of metformin

Answer 1

Inhibit gluconeogenesis in liver activates AMP-activated kinase

Also enhance tissue sensitivity to insulin allowing greater glucose uptake of tissues

Question 2

Name the clinical benefits of metformin

Answer 2

Low risk of hyperinsulinemia and hypoglycemia

Weight loss

Improves lipids

Question 3

How is Metformin absorbed?

Answer 3

Orally

Question 4

How is Metformin distributed?

Answer 4

Rapid distribution

Minimal plasma protein binding

Question 5

Is Metformin metabolized?

Answer 5

No

Question 6

How is Metformin excreted?

Answer 6

Unchanged in the urine

Question 7

What are some of the adverse effects associated with Metformin?

Answer 7

Diarrhea
Vomiting
Indigestion
Anorexia
Increase risk of B12 malabsorption

Question 8

What are some patients that are contraindicated for use of Metformin?

Answer 8

Those with renal problems

Risk of lactic acidosis

Question 9

Describe the mode of action of glipizide

Answer 9

Bind to SU receptor on proteins and inhibit K ATP channel mediated K efflux

This triggers calcium dependent exocytosis of insulin granules from pancreatic beta cells

Question 10

What is a criteria for those who intend to start on glipizide?

Answer 10

Functional beta cells

Question 11

How is glipizide absorbed? What is a special consideration to advice patients?

Answer 11

Oral

Need to be taken before food as absorption can be delayed with food

Question 12

How is the distribution like for glipizide?

Answer 12

Bind extensively to plasma proteins

Question 13

Why is glipizide preferred among the other sulphonylureas?

Answer 13

Lower risk of hypoglycemia

Question 14

What are the adverse effects of glipizide?

Answer 14

Hypoglycemia

Weight gain

Question 15

How is glipizide metabolized?

Answer 15

By the liver via hydroxylation

Question 16

How is glipizide eliminated?

Answer 16

<10% excreted unchanged in urine and feces

Question 17

Why are the elderly more susceptible to hypoglycemia upon taking glipizide?

Answer 17

Poorer renal and liver function

Question 18

Describe the mode of action of Sitagliptin

Answer 18

Binds and inhibit DPP-4 enzymes which are responsible for degrading GLP-1

Therefore, prolongs action of endogenous insulin and suppresses alpha-cell mediated glucagon release.

Inhibits hepatic glucose production

Also can stimulate beta cells and increase glucose-stimulated insulin release.
Thus, decreasing blood glucose

Question 19

How is Sitgliptin absorbed?

Answer 19

Orally

Question 20

How is sitagliptin metabolized and excreted?

Answer 20

Metabolized by low hepatic metabolism and excreted in urine

Question 21

What are the adverse effects of Sitagliptin?

Answer 21

GI disturbances
Flu like symptoms
Skin reaction

Question 22

What are some contraindications to the use of Sitagliptin?

Answer 22

History of pancreatitis

Renal insufficiency

Question 23

Describe the mode of action of Liraglutide

Answer 23

Acts as a GLP-1 receptor agonist by activating GLP-1 receptors on pancreas

Activates adenyl cyclase

Increase cAMP and PKA

Therefore causing a cascade:
1. Increase insulin secretion
2. Decrease glucagon released
3. Delayed gastric emptying
4. Decreases appetite

Question 24

What is a clinical benefit of GLP-1 agonist?

Answer 24

Insulin secretion will subside as blood glucose decrease and achieve euglycemia

Question 25

How is liraglutide absorbed?

Answer 25

SC injection

Question 26

How is liraglutide distributed?

Answer 26

Extended plasma protein binding due to C16 fatty acid binding to plasma proteins

Question 27

How is liraglutide excreted?

Answer 27

Mostly already removed by proteolysis Some removed by faeces and urine

Question 28

What is the advantages and disadvantages of using GLP-1 agonist?

Answer 28

Advantages: Encourages weight loss; Lesser risk of CVD death, non fatal MI and HF Disadvantages: Expensive, possible ADR include acute pancreatitis, dyspepsia and N/V

Question 29

What is the mode of action of empagliflozin?

Answer 29

Inhibition of SGLT2 causes decrease renal reabsorption of filtered glucose. Increased excretion of urinary glucose and decrease renal threshold of glucose

Question 30

What are the clinical benefits of using empagliflozin?

Answer 30

Decreases risk of major cardiac event Decrease risk of worsening end point renal failure

Question 31

What is the ADME of empagliflozin?

Answer 31

A: Oral D: Highly plasma protein bound M: Metabolized in liver via glucuronidation E: Feces and urine

Question 32

What are some of the adverse effects of empagliflozin?

Answer 32

UTI Increased urination Female genital mycotic infection Diabetic ketoacidosis