Flashcards in EXAM #5: ANTIDIABETIC AGENTS Deck (64):
What is the product of alpha cells in the pancreas?
What is the product of beta cells in the pancreas?
Insulin and amylin
What is the product of delta cells in the pancreas?
What is the product of G cells in the pancreas?
What is the product of F cells in the pancreas?
What type of hormone is insulin? What are the implications?
- Peptide hormone that can bind EXTRCELLULAR receptors
*Note that from a therapeutic standpoint, oral insulin is not a viable option
List the factors that will upregulate insulin release?
Epi/ B-2 adrenergic
List the factors that will downregulate insulin release?
Outline the response of the pancreatic beta-cell to glucose.
1) Glucose comes into the cell via the glucose transporter (GLUT-2)
2) Intracellular ATP increases
3) High levels of intracellular ATP cause ATP-sensitive K+ channels to CLOSE
4) Depolarization follows, opening voltage-gated Ca++ channels
5) Ca++ dependent Ca++ release of insulin packaged in secretory vesicles= insulin release
What is the major metabolic response to insulin?
Translocation of GLUT-4 transporters from the cytoplasmic compartment to the membrane
*Especially in skeletal muscle and adipose tissue
What is the major function of GLUT-4 transporters?
Insulin mediated uptake of glucose
Generally, what is the function of insulin action on: 1) fatty acids, 2) glucose, 3) amino acids?
Insulin promotes conversion of smaller molecules to their storage to the storage forms i.e:
1) Fatty acids to TAG
2) Glucose to glycogen
3) Amino acids to protein
What metabolic processes are favored in the absence of insulin?
What is the key difference between Type I and Type II DM?
What is the key pathologic characteristic of Type I DM?
Autoimmune Beta cell destruction leading to absolute insulin deficiency
What is the key pathologic characteristic of Type II DM?
Insulin resistance i.e. increased insulin needed for same effect
What are the signs/sx of Type I DM?
*Remember the 3 P's of Type I DM
What are the signs/sx of Type II DM?
- Obesity/ metabolic syndrome
What is normal fasting blood glucose level?
Less than 100 mg/dL
What is a diabetic fasting blood glucose level?
Roughly 140 mg/dL
What plasma blood glucose level should one be at an hour or so after a meal?
Less than 200 mg/dL
What is the mainstay treatment for Type I DM?
What is the one route that insulin cannot be administrated?
*Note that SQ is most common
What is the purpose of altering amino acids in the beta chain of insulin?
- Alters the "stickiness" of the insulin
- Will complex with other insulin or not
*Implications for duration of action/onset
What has been done to make rapid acting insulin?
Amino acid change so that insulin peptide complexes DO NOT occur
What are the examples of rapid-acting insulin?
What is the onset of rapid acting insulin?
What is the duration of action of rapid-acting insulin?
What is an example of short-acting insulin?
What is the duration of action for short-acting insulin?
What is an example of intermediate acting insulin?
*Forms protamine-insulin complexes
What is the duration of action of intermediate acting insulin?
What are examples of long-acting insulin?
How is insulin formulated to be long-acting?
Forms a precipitate at neutral pH
What is the duration of action for long-acting insulin?
12-20 or 22-24 hours
What type of insulin is used in an insulin pump vs. SQ injection?
Pump= rapid only
SQ= rapid and long-acting
How would you manage eating a meal with insulin?
How are basal levels of insulin maintained?
What is intermediate duration insulin typically used for?
What is the most common adverse effect of insulin? What are other adverse effects seen with insulin theray?
*Also, injection site reactions--lipohypertrophy or lipoatrophy-- that require changing sites*
What are the signs/sx. of hypoglycemia?
How is hypoglycemia treated?
Glucose or glucagon
What is the first line agent to treat DM-II?
What is the MOA of Metformin?
- Decreased hepatic glucose output
- Increased utilization in the peripheral tissue
*Not really understood, but NOT dependent on B-cell function*
What is the key adverse effect with Metformin?
List the sulfonylureas and meglitinides.
What is the MOA of the sulfonylureas and meglitinides?
Inhibit ATP-sensitive potassium channel of the Beta-cell resulting in insulin release
What adverse effects are seen with the sulfonylureas and meglitinides?
What are the Glucosidase inhibitors?
What is the MOA of the Glucosidase inhibitors?
Inhibit the brush border glucosidase enzyme the prevent absorption of glucose
What adverse effects are seen with Glucosidase inhibitors?
When are Glucosidase inhibitors contraindicated?
Patients with pre-existing GI disorder e.g. Lactose intolerance
What are the Thiazolindinediones?
What is the MOA of the Thiazolindinediones?
Generally, increase the expression of GLUT-4
*Increases peripheral glucose uptake
What key adverse effects are associated with Thiazolindinediones?
What is the amylinomimetic drug?
What is the MOA of Pramlintide?
- Inhibit glucagon release
- Inhibit gastric emptying
- Anorectic effect
What are the adverse effects of Pramlintide?
- Delayed drug absorption
What are the incretins?
What is the MOA of the incretins?
Increased insulin secretion by binding to incretin receptors on beta-cells
What adverse effects are associated with the incretins?
What is the normal function of DPP?
Breakdown of incretins
*Incretins normally stimulate insulin release
What are the DPP inhibitors?