Diabetic Agents Flashcards
Describe the mode of action of metformin
Inhibit gluconeogenesis in liver activates AMP-activated kinase
Also enhance tissue sensitivity to insulin allowing greater glucose uptake of tissues
Name the clinical benefits of metformin
Low risk of hyperinsulinemia and hypoglycemia
Weight loss
Improves lipids
How is Metformin absorbed?
Orally
How is Metformin distributed?
Rapid distribution
Minimal plasma protein binding
Is Metformin metabolized?
No
How is Metformin excreted?
Unchanged in the urine
What are some of the adverse effects associated with Metformin?
Diarrhea
Vomiting
Indigestion
Anorexia
Increase risk of B12 malabsorption
What are some patients that are contraindicated for use of Metformin?
Those with renal problems
Risk of lactic acidosis
Describe the mode of action of glipizide
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
What is a criteria for those who intend to start on glipizide?
Functional beta cells
How is glipizide absorbed? What is a special consideration to advice patients?
Oral
Need to be taken before food as absorption can be delayed with food
How is the distribution like for glipizide?
Bind extensively to plasma proteins
Why is glipizide preferred among the other sulphonylureas?
Lower risk of hypoglycemia
What are the adverse effects of glipizide?
Hypoglycemia
Weight gain
How is glipizide metabolized?
By the liver via hydroxylation
How is glipizide eliminated?
<10% excreted unchanged in urine and feces
Why are the elderly more susceptible to hypoglycemia upon taking glipizide?
Poorer renal and liver function
Describe the mode of action of Sitagliptin
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
How is Sitgliptin absorbed?
Orally
How is sitagliptin metabolized and excreted?
Metabolized by low hepatic metabolism and excreted in urine
What are the adverse effects of Sitagliptin?
GI disturbances
Flu like symptoms
Skin reaction
What are some contraindications to the use of Sitagliptin?
History of pancreatitis
Renal insufficiency
Describe the mode of action of Liraglutide
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
What is a clinical benefit of GLP-1 agonist?
Insulin secretion will subside as blood glucose decrease and achieve euglycemia
How is liraglutide absorbed?
SC injection
How is liraglutide distributed?
Extended plasma protein binding due to C16 fatty acid binding to plasma proteins
How is liraglutide excreted?
Mostly already removed by proteolysis
Some removed by faeces and urine
What is the advantages and disadvantages of using GLP-1 agonist?
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
What is the mode of action of empagliflozin?
Inhibition of SGLT2 causes decrease renal reabsorption of filtered glucose.
Increased excretion of urinary glucose and decrease renal threshold of glucose
What are the clinical benefits of using empagliflozin?
Decreases risk of major cardiac event
Decrease risk of worsening end point renal failure
What is the ADME of empagliflozin?
A: Oral
D: Highly plasma protein bound
M: Metabolized in liver via glucuronidation
E: Feces and urine
What are some of the adverse effects of empagliflozin?
UTI
Increased urination
Female genital mycotic infection
Diabetic ketoacidosis
