FDN Exam 2 - T2DM Drugs Lab Flashcards
What class of drugs does Metformin belong to?
biguanide
What is the mode of action of metformin?
Increases tissue sensitivity to insulin and reduces hepatic glucose output
What is the most commonly used initial medication used to treat T2DM?
Metformin
Side effects of Metformin?
Mild nausea (that may promote weight loss)
Advantages of Metformin?
No hypoglycemia, effective at lowering plasma glucose and HbA1c, possible weight loss, and its inexpensive (its the generic!)
What is the MAJOR mode of action of sulfonylureas and meglitinides?
Stimulation of insulin secretion
Where does ATP bind on the ATP-sensitive inward-facing K+ channel in beta cells?
The SUR1 subunit
This binding closes the Kir6.2 subunit, subsequently depolarizing the cell and opening the Ca2+ channels. Ca2+ influx into the cytoplasm triggers the release of insulin
Name three sulfonylurea drugs
Glipizide, glyburide, glimepiride
“-ide”
Name two meglitinides
Nateglinide and repaglinide
“-glinide”
What class of drug is exenatide?
Exogenous incretin agonist
What is an incretin?
When glucose is in the intestine, incretins are released from enteric neurons and circulate in the blood. They bind to the beta cell and “sensitize” the beta cell to release insulin
They also reduce glucagon secretion and slow gastric emptying
Name two endogenous incretins
- Glucagon-like peptide (GLP)
2. Gastric inhibitory polypeptide (GIP)
Name three exogenous incretin agonists
exenatide, lixisenatide, semaglutide
“-tide”
What does glucagon-like peptide 1 do?
It is released within minutes after eating a meal and is known to suppress glucagon secretion and stimulate insulin secretion
What is Lixisenatide and how is it administered + how often?
Glucagon-like peptide 1 receptor agonist (belongs to exogenous incretin agonist drug class)
It is administered subcutaneously once a day
What is semaglutide and how is it administered + how often?
Glucagon-like peptide 1 receptor agonist (belongs to exogenous incretin agonist drug class)
It is administered subcutaneously once a week
Does exogenous insulin increase the activity of incretins?
No
How can we increase the amount of incretins present endogenously?
By decreasing their degradation
DPP-4 degrades incretins so we can inhibit DPP-4
What class of drugs increases endogenous incretins?
DPP-4 blockers
Name four DPP-4 blockers
stigliptin, linagliptin, saxagliptin, alogliptin
“-gliptin”
What is the major mode of action of miglitol and acarbose?
Interference with intestinal starch digestion (by interfering with a-glucosidase)
This decreases glucose entrance into circualtion
What type of drug is pramlintide?
An amylin analogue
What is amylin?
It’s an “islet associated peptide” that is also released by the beta cell along with insulin
It inhibits glucagon secretion, delays gastric emptying, and acts a satiety agent/reduces appetite
What is the MAJOR mode of action of canagliflozin and dapagliflozin?
They increase urinary glucose excretion/decrease kidney glucose reabsorption by blocking SGLT2 in the proximal convoluted tubules
What percentage of filtered glucose does SGLT2 normally reabsorb?
90%
What is the MAJOR mode of action of thiazolidinediones?
Increase tissue sensitivity to glucose by stimulating PPAR-gamma transcription factors
(ultimately they increase FA storage, thus reducing FFA in the blood and increasing the dependence on glucose for fuel/energy)
Can insulin be used to treat T2DM?
Yep
What does miglitol do?
It’s an alpha-glucosidase inhibitor so it decreases intestinal carbohydrate digestion
What does dapagliflozin do?
It’s an SLGT2 blocker that decreases glucose reabsorption in the kidney/increases glucose excretion in urine
What does nateglinide do?
It’s a meglitinide that increases insulin secretion
What does glyburide do?
It’s a sulfonylurea that increases insulin secretion
What does acarbose do?
It’s an alpha-glucosidase inhibitor so it decreases intestinal carbohydrate digestion
What does pramlintide do?
Its an amylin agonist so it decreases glucagon secretion, decreases the rate of gastric emptying, and increases satiety
What three drug classes increase insulin secretion?
Sulfonylureas, Meglitinides, and exogenous incretin agonists
What two drug classes increase tissue sensitivity to insulin?
Metformin (technically biguanide drug class) and thiazolidinediones
What two drug classes decrease glucagon secretion?
Exogenous incretin agonists and exogenous amylin agonists
