Insulin and hypoglycemic agents Flashcards
what are the positive regulators of insulin release?
glucose amino acids incretins EPI / B2 adrenergic vagal
what are the negative regulators of insulin release?
NE / a2 adrenergic
amylin
what is the molecular mechanism of insulin release?
- glucose enters cell
- increase ratio of ATP:ADP generated in the cell
- ATP sensitive potassium channel closes, causing depolarization - stimulates voltage dependent calcium channel
- calcium dependent release of insulin
in which tissues is GLUT4 located?
muscle, adipose
which glucose transporter is regulated by insulin?
GLUT4
what is the role of GLUT4?
insulin mediated uptake of glucose
what are the key signs and symptoms of type I diabetes?
polyuria thirst blurred vision weight loss / polyphagia weakness / dizziness paresthesias level of consciousness
what are the key signs and symptoms of type II diabetes?
infections
neuropathy
classic severe insulin deficiency signs
obesity and metabolic syndrome
what are the pharmacokinetics of insulin therapy?
diffusion in to peripheral tissue rather than into portal circulation - preferential effects on hepatic metabolic processes is less
what is the main route of administration for insulin?
subQ
what is the therapeutic goal of insulin therapy?
fasting blood glucose concentrations between 90-120 mg/dL
what are the rapid acting insulin agents?
insulin lispro
insulin aspart
insulin glulisine
inhaled insulin
what is the short acting insulin?
regular insulin
what is the intermediate acting insulin?
NPH
what are the long acting insulin agents?
glargine
detemir
what are the key features of the rapid acting insulin agents?
amino acid alteration in C-terminal tail of B peptide preventing insulin complex formation
what are the key features of the short acting insulin agent?
identical to human insulin, forms complexes
what are the key features of the intermediate acting insulin agent?
protamine-insulin complex
what are the key features of the long acting insulin agents?
amino acid substitutions that result in precipitate formation at a more neutral pH in the body
what are the kinetics of the rapid acting insulin agents?
onset: 10-30 minutes
peak: 30m - 3h
duration: 3-5h
what are the kinetics of the short acting insulin agents?
onset: 30-60m
peak: 2.5-5h
duration: 4-12h
what are the kinetics of the intermediate acting insulin agents?
onset: 1-2h
peak: 4-8h
duration: 10-20h
what are the kinetics of the long acting insulin agents?
onset: 1-4h
peak: no peak
duration: 12-20h, 22-24h
which insulin agent is good for mimicking management of a meal?
rapid
which insulin agent is good for maintaining basal levels?
long acting
which insulin agent is good for mimicking sleep?
intermediate, NPH
what is the most common adverse effect of insulin therapy?
hypoglycemia hypersensitivity resistance lipohypertrophy lipoatrophy
what is the cause of hypoglycemia in insulin therapy?
insulin therapy is too effective
what is the treatment for hypoglycemia?
glucose or glucagon
what are the symptoms of hypoglycemia?
sympathetic symptoms - irritability, confusion, headache, speech difficulty, blurred vision, tiredness
what is the first line agent for type II diabetes?
metformin
what are the important points about metformin?
does not produce hypoglycemia
not dependent upon beta cell function
what is the MOA of metformin?
- decrease hepatic glucose output
- increase peripheral glucose utilization
- activation of hepatic enzyme AMP-activated protein kinase (AMPK)
peripheral and hepatic effects
what are the adverse effects of metformin?
GI disturbances - poor compliance
vitamin B12 deficiency
what are the sulfonylurea diabetic agents? what are they used for?
glimepiride
glipizide
glyburide
oral antidiabetic agents
what are the meglitinides? what are they used for?
repaglinide
nateglinide
oral antidiabetic agents
what is the MOA of the sulfonylureas and meglitinides?
inhibition of ATP-sensitive potassium channel of B cell, resulting in insulin release
what are the adverse effects of the sulfonylureas and meglitinides?
weight gain
hypoglycemia
what are the glucosidase inhibitors?
acarbose
miglitol
glucosidase inhibitors are contraindicated in what populations?
IBD, GI issues
what is the MOA of the glucosidase inhibitors?
inhibition of brush border glucosidase enzyme and subsequent absorption of glucose
what are the thiazolidinediones (TZDs)?
pioglitazone
rosiglitazone
what is the MOA of the thiazolidinediones (TZDs)?
- decrease peripheral resistance by activating PPAR gamma
2. increase peripheral sensitivity by increasing GLUT4 expression in glucose sensitive tissues
what are the adverse effects of the thiazolidinediones (TZDs)?
peripheral edema hepatotoxicity bone fractures hypoglycemia CV
what is the amylinomimetic agent?
pramlintide
what is the MOA of pramlintide? what type of drug is it?
inhibit glucagon release
inhibit gastric emptying
anoretic effect
amylinomimetic
what are the incretin agents?
exenatide
liraglutide
what is the MOA of the incretins?
potentiate insulin secretion
inhibits glucagon release
inhibits gastric emptying
anoretic effect
what are the dipeptidyl peptidase (DPP) inhibitors?
sitagliptin
saxagliptin
linagliptin
what is the MOA of the dipeptidyl peptidase (DPP) inhibitors?
inhibit incretin degradation
what are the adverse effects of the dipeptidyl peptidase (DPP) inhibitors?
nasopharyngitis upper respiratory infections headaches acute pancreatitis hemorrhagic or necrotizing pancreatitis
