Oral Hypoglycemic Agents Flashcards
What are the cells in the pancreas that secrete: glucagon?
Alpha cells
What are the cells in the pancreas that secrete: insulin and amylin
Beta cells
What are the cells in the pancreas that secrete: Somatostatin
Delta cells
What are the cells in the pancreas that secrete: Gastrin
G cells
What are the cells in the pancreas that secrete: polypeptide
F cells
What are the areas in the pancreas that house beta cells?
Islets of langerhans
Why is oral administration of insulin not an option
Will degrade the peptide hormone
What are the components of insulin?
A chain and B chain linked by a disulfide bond
What is the use of C peptide?
Biologic marker of insulin secretion
What are the chemical that increase the secretion of insulin?
Glucose
Amino acids
Incretin (hormone)
Epi/B2
What nerve innervation will increase insulin secretion?
Vagal stimulation
What is the effect of NE/alpha 2 compounds on insulin release?
Decreases release
What is the effect of amylin on insulin release?
Decreases release
What is the signal for insulin release?
Glucose comes in, causing an increase in ATP/ADP ratio. This will close a Na channel, and open a voltage dependent Ca channel. This Ca will cause release of the insulin vesicles
What is the MOA of insulin?
Binds extracellular receptor, (Y kinase), and causes increase in GLUT 4 transporters to the membrane
Where is GLUT 1 transporters found, and what is its function?
All cells
Basal glucose uptake
Where is GLUT 2 transporters found, and what is its function?
Pancreatic Beta cells, liver
Insulin release
Where is GLUT 3 transporters found, and what is its function?
Brain, kidney
Neuronal uptake
Where is GLUT 4 transporters found, and what is its function?
Muscle adipose tissue
Insulin mediated uptake
Where is GLUT 5 transporters found, and what is its function?
Gut, kidney
Fructose uptake
Which GLUT transporter is regulated by insulin?
GLUT 4
What is the effect of insulin on triglycerides?
Increase FA synthase
What is the effect of insulin on glycogen?
Increases synthesis and storage
What is the effect of insulin on proteins?
Increases synthesis
What is the effect of glucose on Glycogen stores?
Increase degradation and release
What is the effect of glucose on Fat stores?
Increase Keto acids
What is the effect of glucose on glycolysis?
Decreases
What is type 1a DM? 1b?
1a = autoimmune 1b = idiopathic
What genetic conditions lead to DM?
Mutations in the insulin receptors
What is the major endocrinopathy that leads to DM?
Somatostatinoma
What happens in early in the onset of DM II with insulin levels?
Initially increase
What causes the blurred vision with DM?
Hyperosmolar state
What are the ssx of DM II?
Infections, neuropathies
Could get classic insulin deficiency signs, but rare
What is the normal range of fasting glucose levels?
DM = more than 126
Pre DM = more than 110
What are the levels of casual plasma glucose in DM?
Greater than 200
Why is it important to bypass the liver with insulin administration?
Less preferential metabolic effects on the liver
What is the therapeutic goal of insulin treatment?
BG between 90 -120
How many units should be given to a pt?
Varies between pts, with weight and personal
How do we prevent/encourage insulin from sticking to each other? Why do this?
Alter amino acids in the B chain.
Alters pharmacokinetics
What is the onset of duration of action for rapid acting insulin?
10-30 mins
3-5 hours
What is the onset and duration of action for short acting insulin?
30-60 mins
4-12 hours
What is the onset and duration of action for intermediate acting insulin?
12- hours
10-20 hours
What is the onset and duration of action for long acting insulin?
1-4 hours
12-20 hours
What is the chemical alteration for rapid acting insulin?
Amino acid alteration in the C terminal tail of the B peptide, preventing complex formation
Rapid, short, intermediate, or long acting: insulin lispro
Rapid
Rapid, short, intermediate, or long acting: insulin aspart
Rapid
Rapid, short, intermediate, or long acting: insulin glulisine
Rapid
Rapid, short, intermediate, or long acting: inhaled insulin
Rapid
Rapid, short, intermediate, or long acting: regular insulin
Short
Rapid, short, intermediate, or long acting: NPH
Intermediate
Rapid, short, intermediate, or long acting: Glargine
Long
Rapid, short, intermediate, or long acting: Detemir?
Long
What is the chemical alteration with long acting insulin?
Amino acid substitution that results in precipitate formation at a more neutral pH in the body
What is the chemical alteration in intermediate acting insulin?
Protamine-insulin complex
What are the insulin types that a pump holds?
Rapid and short acting
What combination of insulin do people who inject insulin regularly (not a pump) use?
Short and long acting
Trying to mimic basal levels of BG, what type of insulin should be used?
Long acting
Handling a meal is best for what type of insulin?
rapid
What are the two rare adverse effects of insulin?
Hypersensitivity and resistance
What are the injection site adverse effects of insulin?
Lipohypertrophy and lipoatrophy
What is the most common side effect of insulin use?
Hypoglycemia–insulin therapy too effective
What is the treatment for hypoglycemia in DM I pts?
Use glucagon or feed
What are the ssx of hypoglycemia?
Tachycardia Sweating Tremors Nausea Hunger
What are the neuroglycopenic symptoms?
Irritability, confusion, HA
Blurred vision
True or false: use glucagon liberally if ssx of hypoglycemia are present
True
What is the MOA of metformin (2)?
Decreases hepatic glucose output
Increases peripheral glucose utilization
Does metformin cause a hypoglycemia?
No
What are the adverse effects of metformin? (2, short/long term)
GI disturbances
Vit B12 deficiency with long term use
What are the adverse effects of Sulfonylureas and Meglitindies?
Weight gain
Hypoglycemia
What are the sulfonylureas? MOA?
Glimepiride
Glipizide
Glyburide
Inhibit K channel, causing insulin release
What are the Meglitinides? MOA?
Repaglinide
Nateglinide
Inhibit K channel, causing insulin release
What is the MOA of acarbose? Adverse effects?
Inhibit brush border glucosides enzyme and subsequent absorption of glucose
GI distubances
What is the MOA of Miglitol? Adverse effects?
Inhibit brush border glucosides enzyme and subsequent absorption of glucose
GI disturbances
What are the two Thiazolidinediones? MOA?
piolitazone
rosiglitazone
Increase GLUT 4 transcription
What are the two major DM II drugs that cause hypoglycemia?
Sulfonylureas
Thiazolidinediones
What is the one amylinomimetic drug?
Pramlintide
What is the MOA of pramlintide? Side effects?
Inhibit glucagon release and gastric emptying
n/v hypoglycemia
Delayed drug absorption
What are the two incretins?
Exenatide
Liraglutide
What are the three DPD inhibitors?
Sitagliptin
Saxagliptin
Linagliptin
What is the MOA of DPDs? Adverse effects?
Inhibit incretin degradation
Acute pancreatitis (hemorrhagic or necrotizing)
What is the MOA of Glimepiride? Use? Adverse effects?
Sulfonylurea-inhibits ATP sensitive K channels, causing insulin release
DM II
Weight gain and hypoglycemia
What is the MOA of Glipizide? Use? Adverse effects?
Sulfonylurea-inhibits ATP sensitive K channels, causing insulin release
DM II
Weight gain and hypoglycemia
What is the MOA of Glyburide? Use? Adverse effects?
Sulfonylurea-inhibits ATP sensitive K channels, causing insulin release
DM II
Weight gain and hypoglycemia
What is the MOA of Repaglinide? Use? Adverse effects?
Meglitinide-inhibits ATP sensitive K channels, causing insulin release
DM II
Weight gain and hypoglycemia
What is the MOA of Nateglinide? Use? Adverse effects?
Meglitinide-inhibits ATP sensitive K channels, causing insulin release
DM II
Weight gain and hypoglycemia
What is the MOA of Acarbose? Use? Adverse effects?
Glucosidase inhibitor
DM II
Diarrhea, flatulence
What is the MOA of Miglitol? Use? Adverse effects?
Glucosidase inhibitor
DM II
Diarrhea, flatulence
What is the MOA of Pioglitazone? Use? Adverse effects?
Thiazolidinedione–Increases translation of GLUT4
DM II
Hepatotoxic, cardio effects
What is the MOA of Rosiglitazone? Use? Adverse effects?
Thiazolidinedione–Increases translation of GLUT4
DM II
Hepatotoxic, cardio effects
What is the MOA of metformin? Use? Side effects?
Decreases glucose output from liver, increases insulin sensitivity
DM II
GI disturbances
What is the MOA of Pramlintide? Use? Side effects?
Inhibit glucagon release and gastric emptying
DM II
n/v hypoglycemia
What is the MOA of Exenatide? Use? Side effects?
incretin–increases insulin release, inhibits glucagon
DM II
Pancreatitis, hypoglycemia
What is the MOA of Liraglutide? Use? Side effects?
incretin–increases insulin release, inhibits glucagon
DM II
Pancreatitis, hypoglycemia
What is the MOA of Sitagliptin? Use? Side effects?
DPP-Inhibits incretin degradation
DM II
Acute pancreatitis
What is the MOA of Saxagliptin? Use? Side effects?
DPP-Inhibits incretin degradation
DM II
Acute pancreatitis
What is the MOA of Linagliptin? Use? Side effects?
DPP-Inhibits incretin degradation
DM II
Acute pancreatitis