Diabetes Pharmacology Flashcards
What chemical is in the mouth utilized for the digestion of carbs?
Alpha Amylase
What chemicals are in the small intestine that are utilized for the digestion of carbohydrates?
Alpha Amylase, Hydrolases, Glucosidases
What is the role of insulin in carbohydrate homeostasis?
Leads to storage of glucose, synthesized in pancreas, released in response to increasing blood glucose levels
What is the role of glucagon in carbohydrate homeostasis?
Stimulates release of glucose, synthesized in the pancreas, and prevents hypoglycemia
Glucogneogenesis
Formation of glucose not from glycogen
Glycogenolysis
Formation of glucose from glycogen
Glycolysis
Breakdown of glucose for energy
Glycogenesis
Formation of glycogen
Lipolysis
Breakdown of fat
Lipogenesis
Formation of fat
Beta Cells in the Pancreas do what?
Produce insulin and amylin
Insulin and C-Peptide are stored and CO-released together
Alpha Cells in the Pancreas do what?
Regulate glucagon secretion and hepatic glucose output
What is the Primary regulator of insulin release?
Glucose
What are the steps in insulin release?
- glucose into beta cells by FACILITATED diffusion (GLUT1)
- glucokinase phosphorylates glucose to Glucose 6 Phosphate
- glucose 6 phosphate INCREASES ATP levels via glycolytic pathway
- increased ATP:ADP ratio INHIBITS K+ Channels
- membrane depolarization of B cell, INFLUX of Ca2+
- calcium influx leads to EXOCYTOSIS of INSULIN granules
- insulin secretion via incretins
What does SUR (Sulfonylurea Receptor) do?
Block of SUR keeps K+ Channel Closed = Facilitation of Insulin Secretion with no regard to glucose levels
Does IV or Oral Glucose cause a higher Incretin Effect?
Oral (ingestion) of glucose causes more insulin release than an equivalent rise in blood glucose induced by IV, due to it going through the GI tract
What gut derived hormones are released proportionally to nutrient load?
GLP-1 and GIP
What type of diabetes has an impaired incretin effect?
Type 2, worse insulin response/release
How does the insulin receptor cause glucose transportation?
- insulin binds to the receptor
- receptor TYROSINE phosphorylates
- casacade activated
- PIP3 and Akt involved in translocation GLUT4 to cell membrane
- Glucose transported into the cell
Where are insulin receptors located?
Liver, muscle, and fat = ALL peripheral tissues
Where is GLUT4 located?
ON the cell MEMBRANE, important for storage of glucose
What does insulin activate for phosphorylation of glucose in the liver?
Hexokinase = trapping phosphorylated glucose in liver
What enzymes does insulin activate for glycogen synthesis?
Phosphofructokinase and Glycogen Synthase = promoting production of glycogen from excessive glucose
How are fatty acids exported from the liver?
Lipoproteins
How does insulin resistance affect the liver?
Gluconeogenesis causes glucose production despite hyperglycemia, glucagon is not inhibited
How does insulin resistance affect the muscle?
Decreased ability to take up glucose
How does insulin resistance affect the adipocytes?
Lipase enzyme is not inhibited leading to increased plasma FFA and decreased ability to take up glucose
What are the functions of Amylin?
Slows gastric emptying, decreases speed of glucose absorption, suppresses glucagon output, increases satiety, and is co-released with insulin
What type of insulin is used for bolus/prandial dosing?
Rapid
What type of insulin is used for basal dosing?
Long/Ultra Long
Why must you always pair insulin with food?
HYPOglycemia
What is the inhaled insulin on the market?
Afrezza
What is the artificial pancreas on the market?
Medtronic MiniMed
What are the adverse effects of insulin?
Hypoglycemia, Weight Gain, and Insulin Allergy
What is the MOA of Sulfonylureas?
Increase insulin release from beta cells in pancreas by closing K-ATP channels SUR, decreases serum glucagon
Are sulfonylureas independent or dependent on glucose?
Insulin Secretion is INDEPENDENT, risk of hypoglycemia
What drugs are classified as Sulfonylureas?
Glyburide, Glipizide, and Glimepiride
What is the MOA of Meglitinides/Glindies?
Block ATP sensitive potassium channels in beta cells to increase insulin release
Are Meglitinides/Glindies independent or dependent of glucose?
Insulin release, somewhat DEPENDENT on glucose levels, less risk of hypoglycemia
What drugs are classified as Meglitinides/Glinides?
Repaglinide and Nateglinide
What are the pearls of Repaglinide?
Hypoglycemia possible, weight gain, Glucuronidation required for metabolism
What are the pearls of Nateglinide?
Risk of hypoglycemia and weight gain
What is the MOA of Biguanides?
Increases insulin sensitivity in muscle and liver involving activation of AMP Kinase (AMPK), decreases hepatic glucose formation, and stimulation of glucose uptake by increasing GLUT4
Is Biguanide dependent on functioning beta-cells?
NO
What drugs are classified as Biguanide?
Metformin
What are the pearls of Metformin?
Rare hypoglycemia, EUGLYCEMIC Agent, do not use with impaired kidney function, GI upset/diarrhea
What is the MOA of Thiazolidinediones?
Agonists at PPAR-y, nuclear receptor, encouraging redistribution of fat from central to periphery, increases secretion of adiponectin
Are Thiazolidinediones independent or dependent on insulin?
DEPENDENT, REQUIRE insulin to be present for them to work
What drugs are Thiazolidinediones?
Pioglitazone and Rosiglitazone
What are the pearls of Pioglitazone and Rosiglitazone?
Raise HDL levels, weight gain, CHF (black box), increased bone fracture, decreased hematocrit
What is the MOA of A-Glucosidase Inhibitors?
Inhibition of a-glucosidase in intestines, delay digestion and absorption of starch, inhibit glucose uptake from GI
What drugs are A-Glucosidase Inhibitors?
Acarbose and Miglitol
What are the pearls of Acarbose and Miglitol?
No weight gain, no effect on plasma lipids, no hypoglycemia, flatulence, diarrhea, abdominal pain, and bloating
What is the MOA of GLP-1 Agonists?
GLP-1 receptor activation increases cAMP levels, increasing insulin synthesis and release in a glucose-dependent manner
What drugs are classified as GLP-1 Agonists?
Exenatide, Liraglutide, Albiglutide, and Dulaglutide
What are the pearls of Exenatide, Liraglutide, Albiglutide, and Dulaglutide?
N/V (dose dependent), weight loss, and pancreatitis
What drug is a GLP-1 and GIP Agonist?
Tirzepatide/Mounjaro
What are the pearls of Tirzepatide?
Decrease A1c and BW, nausea/diarrhea, vomiting, dyspepsia, acute pancreatitis, acute gallbladder dysfunction, black box for c-cell thyroid tumors
What is the MOA for DPP-4 Inhibitors?
Block degradation of GLP-1 and GIP by dipeptidyl peptidase 4, increasing levels of GLP-1 and GIP
What drugs are classified as DPP-4 Inhibitors?
Alogliptin, Sitagliptin, Saxagliptin, and Linagliptin
What are the pearls of Alogliptin, Sitagliptin, Saxagliptin, and Linagliptin?
No satiety or gastric emptying effects
What is the MOA of Amylin analogs?
Slows gastric emptying, decreases appetite, decreases glucagon release
What drug is classified as an Amylin analog?
Pramlintide
What are the pearls of Pramlintide?
Weight loss and N/V
What is the MOA of SGLT2 Inhibitors?
Inhibits SGLT2, causing less glucose reabsorption, increase glucose in urine
What drugs are classified as SLGT2 Inhibitors?
Canagliflozin, Dapagliflozin, and Empagliflozin
Are SGLT2 Inhibitors dependent or independent of insulin?
Independent
What are the pearls of Canagliflozin, Dapagliflozin, and Empagliflozin?
Low risk of hypoglycemia, some weight loss, and glucose in urine = increase UTIs
What does SGLT2 stand for?
Sodium glucose transporter 2
