PHARM Chapter 30 - Endocrine Pancreas and Glucose Homeostasis Flashcards
ME of
Acarbose
Miglitol
Voglibose
Alpha-Glucosidase Inhibitors - Carbohydrate analogues that bind avidly to intestinal brush border alpha-glucosidase enzymes - slowing breakdown and absorption of dietary carbohydrates (starch, dextrin, disaccharides)
Uses of
Acarbose
Miglitol
Voglibose
Type 2 diabetes mellitus
Continued use of alpha-glucosidase inhibitor associated with
diminishement of GI distress
Alpha-glucosidase inhibitors most useful for patients w
postrpandial hyperglycemia
new-onset patients w/ mild glycemia
Alpha-glucosidase ihibitors contraindicated in
Inflammatory bowel disease - delivery of undigested carbohydrates to distal bowel provides nutrients for colonic bacteria
ME of exogenous insulin
Classic anabolic hormone, promotes carbohydrate metabolism and facilitates glucose, amino acid, and triglyceride uptake and storage in liver, cardiac, and skeletal muscle, and adipose tissue
4 Prandial bolus exogenous insulins
Regular Insulin
Insulin lispro
Insulin aspart
Insulin glulisine
3 Basal “long-acting” exogenous insulins
NPH insulin
Insulin glargine
Insulin detemir
Uses of exogenous insulin
Diabetes mellitus
How are exogenous insulins delivered
parenternally, subcutanous is most commpon
Intermediate acting insulin that contains protamine which prolongs the time required for absorbtion
NPH insulin
Prandial bolus insulins
act rapidly, used to mimic B-cell release of insulin in response to nutreitn load
How is regular insulin stabilized for use and how long is it’s time of onset?
addition of zinc ions
30 minutes
NPH Insulin is formed how?
regular insulin suspended with zinc and protamine (arginine rich protien isolated from fish sperm) - peak activity occurs between 4-10 hours after administration, associated w/ increased hypoglycemia
Major SE of insulin therapy
in absence of carbs can result in hypoglycemia
What are the mainstay treatment for type 2 diabetics
sulfonylureas
4 first-generation sulfonylureas
acetohexamide
chlorpropamide
tolazamide
tolbutamide
5 second-generation sulfonylureas
glimepiride glipizide glibenclamide (glyburide) glicclazide gliquidone
ME of Sulfonylureas
inhibit B-cell K/ATP channel at SUR1 subunit - stimulates insulin release form pancreatic B cells and increase circulating insulin to lvels sufficient to overcome insulin resistance
Major adverse effect of SUlfonylureas
hypoglycemia from oversecretion of insulin
can cause weight gain secodnary to increased insulin activity in adipose tissue (better for nonobese)
Differences between first and second generation sulfonylureas in dosing
first generation bind w/ lower affinity to SUR1 so they must be administered at higher doses
ME of meglitinides
Inhibit B-cell K/ATP channel at SUR1 subunit - stimulate insulin release from pancreatic B-cells and increase circulating insulin to levels sufficient to overcome insulin resistance
2 meglitidines
Nateglinide
Repaglinide
Sulfonylureas may displace endogenous ___ which binds to SUR1 to activate the channel
MG-ADP
How are sulfonylureas delivered
orally
ME of metformin
activates AMP-dependent protein kinase to block synthesis of fatty acids and to inhibit hepatic gluconeogenesis and glycogenolysis - increases insulin receptor activity and metabolic responsiveness in liver and skeletal muscle
Uses of Metformin
type 2 diabetes mellitus
polycystic ovarian syndrome
SE of metformin
lactic acidosis, GI distress
Biguanides (metformin) have what additional benefit?
lowering of serum lipids, decrease in weight
Why do Biguanides (metformin) cause lactic acidosis
decrease flux of metabolic acids through gluconeogenic pathways
ME of pramlintide
Co-released w/ insulin from B-cell acts on receptors in CNS to slow gastric emptying - reduces postrpandial glucagon and glucose release - promotes satiety (amylin analogue)
Uses of pramlintide
Type 1 and Type 2 diabetes
Why can both type 1 and 2 diabetics benefit from pramlintide
type 1 lack endogenous amylin
type 2 deficient in amylin
Added bonus of pramlintide
modest weight loss
SE of pramlintide
nausea
ME of GLP-1 analogues
Exenatide
Liraglutide
Act on GLP1 receptor to enhance glucose-dependent insulin secretion, inhibits glucagon secretion, delays gastric emptying and decreases appetite
ME of DDP-4 inhibitors
Sitagliptin
Saxagliptin
Prolongs GLP-1 activity to enhance glucose-dependent insulin secretion, inhbits glucagon secretion, delays gastric emptying and decreases appetite
Uses of Exenatide
liraglutidde
sitagliptin
saxagliptin
Type 2 diabetes mellitus
SE of exenatide
liraglutide
sitagliptin
saxagliptin
hypoglycemia
most common sideeffect of exenatide and liraglutide
nausea - acute pancreatitis is possible
2 Thiazolidinediones
Pioglitazone
Rosiglitazone
ME of pioglitazone and rosiglitazone
bind and stimulate the nuclear hormone receptor peroxisome proliferator-activated receptor-gamma (PPARy), increases insulin sensitivty in adipose tissue, liver, muscle
Uses of pioglitazone, rosiglitazone
type 2 diabetes mellitus
Why do TZDs not induce hypogycemia
do not increase insulin levels
What main role do TZDs play in treatment
sensitizers - enhance action of insulin at target tissues
SE of rosiglitazone
MI, heart failure, weight gain, edema, bone fractures
ME of diazoxide
Binds to SUR1 subunit of K/ATP channels in pancreatic B-cells and stabilizes ATP-bound (open) state of the channel so that B-cells remain hyperpolarized - decreases insulin secretion by cells
Uses of diazoxide
Hypoglycemia due to hyperinsulinism
malignant hypertension
By what mechanism is diazoxide used off label to treat elevated BP in hypertensive emergencies
hyperpolarizes SUR2 channels in cardiac and smooth muscle cells
Why is oral combination therapy beneficial
drugs have different MEs so lower doses can be used to have glycemic control
octreotide is a ___ analogue
somatostatin - blocks hormone release
What is used to treat severe hypoglycemia
glucagon via subcutaneous injection
What other purposes is glucagon used for
intestinal relaxant before radiographic or MRI
