chapter 30- pharm of endocrine pancreas & glucose homeostasis Flashcards
what are the alpha-glucosidase inhibitors
acarbose, miglitol, voglibose
what is the clinical application of acarbose, miglitol, voglibose
type 2 DM
what are the common adverse effects of acarbose, miglitol, voglibose
abdominal pain, diarrhea, flatulence, elevated serum aminotransferase levels, elevated plasma triglycerides
what are the contraindications for acarbose, miglitol, voglibose
cirrhosis, diabetic ketoacidosis, severe digestive problems, IBD, bowel obstruction
who are acarbose, miglitol, voglibose most useful in
patients with predominant postprandial hyperglycemia and for new-onset hyperglycemia
what are the prandial bolus insulins
regular insulin, lisper, aspart, glulisine
what are the basal long-acting insulins
NPH, glargine, detemir
what basal insulin is a protamine
NPH insulin
what is the alteration of glargine from regular insulin
replaced asparagine A21 with glycine and added 2 arginines after B30
what is the alteration of determir from regular insulin
it is attached to the side chain of lysine B29
what are the common adverse effects of exogenous insulin
hypoglycemia, injection site reaction, lipodystrophy
what is the contraindication for exogenous insulin
hypoglycemia
how much time before a meal must regular insulin be administered
30 minutes
what is the intermediate acting exogenous insulin
NPH
what is the mechanism of action of sulfonylureas and meglitinides
inhibit the beta-cell K+/ATP channel in the SUR1 subunit, thereby stimulating insulin release from pancreatic beta cells & increasing circulating insulin to levels sufficient to overcome insulin resistance
what are the 1st generation sulfonylureas
acetohexamide, chlorpropamide, tolaxamide, tolbutamide
what are the 2nd generation sulfonylureas
glimepiride, glibepiride, glibenclamide, gliclazide, gliquidone
what are the adverse effects of sulfonylureas
hypoglycemia, rash, diarrhea, nausea, dizziness, marginal decrease in circulating lipids
what is the contraindication for sulfonylurea use
diabetic ketoacidosis
what metabolizes sulfonylureas
liver
how can sulfonylureas cause weight gain
secondary to increase insulin activity in adipose tissues
what are the meglitinides
nateglinide, repaglinide
what are common side effects of nateglinide, repaglinide
hypoglycemia, diarrhea, nausea, respiratory infection
what are the contraindications of nateglinide, repaglinide
diabetic ketoacidosis, type 1 DM
what is the mechanism of action of the biguanides
activates AMPK to block synthesis of fatty acids and to inhibit hepatic gluconeogenesis and glycogenolysis; increases insulin receptor activity & metabolic responsiveness in liver & skeletal muscle
what is the most common biguanide
metformin
what are the clinical applications of metformin
type 2 DM; polycystic ovarian syndrome (off label)
what are the common side effects of metformin
lactic acidosis, diarrhea, dyspepsia, cobalamin deficiency, mild GI distress
what are the contraindications for metformin use
heart failure, septicemia, alcohol abuse, hepatic disease, respiratory disease, renal impairment, iodinated contrast media if acute alteration of renal function is suspected, as this may result in lactic acidosis, metabolic acidosis
how does metformin effect serum lipids and weight
lowers serum lipids and decreases weight
what are the changes made to the amylin analogue pramlintide that makes it different from amylin
3 pralines replace an alanine and 2 serines of amylin
what are the clinical applications of pramlintide
type 1 AND 2 DM
what are the common adverse effects of pramlintide
nausea, promotes saiety
what are the contraindications for pramlintide use
hypoglycemia, gastroparesis
how is pramlintide administered
IV before meals
what is the mechanism of action of GLP1-analogues
act on GLP-1 to enhance glucose-dependent insulin secretion, inhibit glucagon secretion, delay gastric emptying, and decrease appetite
what is the mechanism of action of DDP4 inhibitors
prolong GLP-1 activity enhance glucose-dependent insulin secretion, inhibit glucagon secretion, delay gastric emptying, and decrease appetite
what are the GLP-1 analogues
exenatide and liraglutide
what are the adverse effects of exenatide and liraglutide
hypoglycemia, nausea, vomiting, headache
what are the contraindications for exenatide and liraglutide
Type 1 DM, diabetic ketoacidosis
how are exenatide and liraglutide administered
subcutaneous injection
what are exenatide and liraglutide typically used in combination with
metformin or a sulfonylurea
what are the DPP-4 inhibitors
sitagliptin, saxagliptin
what are common side effects of sitagliptin, saxagliptin
URI, nasopharyngitis, headache, mild increase in serum creatinine level
what are the contraindications of sitagliptin, saxagliptin
type 1 DM, diabetic ketoacidosis
what can happen when sitagliptin, saxagliptin are used in combination with sulfonylureas and insulin
may cause hypoglycemia
what is exenatide originally isolated from
salivary gland of the gila monster
what is the mechanism of action of Thiazolidinediones (TZDs)
bind and stimulate the PPARgamma, thereby increasing insulin sensitivity in adipose tissue, liver, and muscle
what are the TZDs
ploglitazone and rosiglitazone
what is the clinical application of ploglitazone and rosiglitazone
type 2 DM
what are the common adverse effects of ploglitazone and rosiglitazone
heart failure, cholesterol hepatitis, hepatotoxicity, diabetic macular edema, increased HDL and LDL, decreased circulating triglycerides and free fatty acids
what are the contraindications of ploglitazone and rosiglitazone
heart failure, MI
what drug is restricted to use in patients that did not respond to other anti-diabetic medications
rosglitazone
what is the mechanism of action of diazoxide
binds to SUR1 subunit of K+/ATP channels in pancreatic beat cells and stabilizes the ATP-bound (open) state of the channel so that the beta cells remain hyper polarized
what is the clinical application of diazoxide
hypoglycemia due to hyperinsulinemia, malignant HTN (off-label)
what are the common adverse effects of diazoxide
fluid retention, bowel obstruction, pancreatitis, thrombocytopenia, extrapyramidal disease, angina, hirsutism
what are the clinical applications of exogenous glucagon
hypoglycemia (severe), intestinal relaxation before radiography of GI tract
what are the common adverse effects of exogenous glucagon
rash, nausea, vomiting
what is the major contraindication of exogenous glucagon
known pheochromocytoma
what does the hyperglycemia action of glucagon depend on
sufficient hepatic store of glycogen
what secretes leptin
adipocytes
what is the transcription factor that serves as the master regulator of adipose cell differentiation and plays an important role in lipid metabolism
PPARgamma
what results from PPARgamma activation
decreases serum free fatty acid levels and increases lipogenesis in adipose tissue
what is the target tissue of amylin
CNS
what is the target system of leptin
CNS (basomedial hypothalamus)
what does AMPK do in low energy states
triggers shift from anabolic to catabolic activities
how does glucose enter beta cells
via GLUT2
what tetramer forms the pore of the K+/ATP channel
Kir6.2