Insulins Flashcards
Islet of Langerhans secrete
insulin, glucagon, somatostatin, pancreatic polypeptide
Beta cells in islet of langerhans synthesize and secrete
insulin
alpha cells in islet of langerhans secrete
glucagon
glucagon
regulates carbs, fats, and protein metabolism
insulin
regulates carbs, fats, and protein metabolism
promotes storage of glucose, fatty acids, and amino acids
activation of Na/K ATPase in cell membranes by insulin moves ___
K+ into cells and decreases concentration of K+ in plasma
Which organ is primary source of endogenous glucose production following glycogenolysis and gluconeogenesis?
liver
What does glucagon stimulate and inhibit?
stimulates: glycogenolysis and gluconeogenesis
inhibits: glycolysis
Glycogenolysis
glycogen breakdown
blood glucose level range that can be regulated
50-300 (narrow)
insulin is released in response to ___
beta-adrenergic stimulation or acetylcholine
insulin release is inhibited in response to ___
alpha adrenergic stimulation or beta-blockade
insulin resistance
impaired intracellular signal decreases the recruitment of proteins that transport glucose to plasma membrane for glucose intake
what inhibits insulin secretion?
hypoglycemia, beta adrenergic antagonists, alpha adrenergic agonists, somatostatin, diazoxide, thiazide diuretics, volatile anesthetics, insulin
principle stimulation for glucagon secretion
hypoglycemia
glucagon
increases blood glucose by stimulating glycogenolysis in liver, activates adenylate cyclase for cAMP formation
type 1 diabetes mellitus
autoimmune mediated destruction of pancreatic beta cells, depend on exogenous insulin to regulate metabolism
type 2 diabetes mellitus
peripheral insulin resistance with failure to secrete insulin because of pancreatic beta cell dysfunction
elevated blood glucose levels and hypoinsulinemia leads to
diabetic myopathy, inhibition of lipase enzyme system, unopposed mobilization of fatty acids, formation of ketones, ketoacidosis, depletion of K
diabetics can have impaired vasodilation that leads to
chronic proinflammatory, prothrombotic, and proatherogenic state and vascular complications
diagnosis of diabetes
elevated fasting glucose > 126 or HbA1c of 6.5% or higher
for T1DM: glucose >200 and HbA1C>7%
long term complications of diabetes
retinopathy, kidney disease, HTN, CAD, peripheral/cerebral vascular disease, neuropathy
treatment for Type 1 DM
insulin
basal supplementation + short acting before food absorption
need at least 2 daily SQ injections of intermediate or long acting + rapid acting following meals
Intermediate acting basal insulins
NPH, lente, lispro protamine, aspart protamine
twice daily administration
long acting basal insulins
ultra lente, glargine, detemir
once daily
short acting insulin
regular
meal time
rapid acting insulin
lispro, aspart, glulisine
meal time
what is the most commonly used commercial preparation of inuslin?
Insulin U-100 (100u/mL)
typical daily exogenous dose of insulin for T1DM
0.5-1 u/kg/day (40-80units/day)
onset, peak, duration of rapid acting insulin
onset: 5-15 minutes
peak: 45-75 minutes
duration: 2-4 hours
onset, peak, duration of short acting insulin
onset: 30 minutes
peak: 2-4 hours
duration: 6-8 hours
onset, peak, duration of intermediate acting insulin
onset: 2 hours
peak: 4-12 hours
duration: 18-28 hours
onset, peak, duration of long acting insulin
onset: 1.5-2 hours
peak: 3-9 hours, none
duration: 6->24 hours
what preparations are used for continuous insulin pumps?
short acting (regular) and rapid acting (lispro, aspart, glulisine)
lispro onset, peak, duration
onset: 15 minutes
peak: 45-75 minutes
duration: 2-4hours
administration of regular insulin
IV or SQ
five main side effects of insulin
hypoglycemia, allergic reactions, lipodystrophy, insulin resistance, drug interactions
first symptoms of hypoglycemia are compensensatory effects of ___
increased epinephrine secretion
first symptoms of hypoglycemia include
diaphoresis, tachycardia, HTN, rebound hyperglycemia from SNS activation, mental confusion, seizures, coma
prolonged hypoglycemia can lead to
irreversible brain damage because the brain depends on glucose for oxidative metabolism
severe hypoglycemia treatment
50-100mL of 50% glucose IV
0.5-1.0mg IV/SQ glucagon
chronic protamine exposure in NPH may stimulate production of antibodies against __
protamine (worry aboutin CABG)
hormones that counter hypoglycemic effects of insulin
adrenocorticotrophic hormone, estrogen and glucagon
epinephrine ____ insulin secretion and ____ glycogenolysis
inhibits; stimulates
which drugs increase duration of action of insulin?
tetracycline, salicylates, phenylbutazone
four major classes of oral antidiabetic drugs
secretagogues, biguanides, thiazolidinediones or glitazones, alpha-glucosidase inhibitors
how do sulfonylureas work?
stimulate insulin secretion
how do biguanides (metformin) work?
inhibit glucose production by the liver by activating adenosine monophosphate activated protein kinase
contraindications for metformin
lactic acidosis, AKI, GI intolerance, acute hepatic disease
metformin
does not undergo metabolism, not bound to plasma proteins
elimination half time of metformin
2-4 hours
dose of metformin
500-1000mg TID with meals
when should patients discontinue metformin before surgery?
48 hours before surgery
do not give metformin to patients with:
hepatic dysfunction, renal insufficiency, IV contrast dye, acute MI, CHF, arterial hypoxemia, sepsis
in order for sulfonylureas to be successful patients need to have
some beta cell function
do not administer sulfonylureas if the patient has
a sulfa allergy
MOA of sulfonylureas (glyburide, glipizide, glimepride)
act on sulfonylurea receptors on pancreatic and cardiac cells, inhibit adenosine triphosphate sensitive K+ channels on pancreatic beta cells = Ca2+ influx and stimulation of insulin release
glyburide
dose: 2.5- 20mg daily
peak: 3 hours
DOA: 18-24 hours
elimination half time: 4.5-12 hours
glipizide
dose: 5-40mg daily
peak: 1 hour after PO
DOA: 12-24 hours
elimination half time: 4-7 hours
glimepiride
dose: 2-4 mg daily
DOA: 24+ hours
elimination half time: 5-8 hours
meglitinides exert effects on
beta cells
meglitinides MOA
lowers blood glucose by stimulating release of insulin from beta cells
nateflinide (starlix) unique characteristic
accumulation of active metabolites may cause hypoglycemia
difference between repaglinide and nateflinide
repaglinide - nateglinide-
minimal kidney excretion excreted by kidney
alpha glucosidase inhibitors MOA
decrease carbs digestion and absorption of disaccharides by interfering with intestinal glucosidase activity
thiazolidinediones MOA
act at skeletal muscle, liver, and adipose tissue via peroxisome proliferator activator receptor-gamma to decrease insulin resistance and hepatic glucose production, and to increase use of glucose by liver
which patients are thiazolidinediones more effective?
obese patients
how long does it take to reach clinical effect for thiazolidinediones
4-12 weeks
when are thiazolidinediones contraindicated?
CHF, liver failure
glucagon like peptide 1 receptor agonists MOA
increase insulin secretion from beta cells, decrease glucagon production from alpha cells and reduce gastric emptying
dipeptidyl peptidase 4 inhibitors MOA
increase insulin secretion from alpha cells and reduce pancreatic alpha cell secretion of glucagon
pramlintide (amylin agonist) MOA
suppress gastric emptying, inhibit glucagon release and reduce HbA1C but does not alter insulin levels!
goal of combination therapy
target two or more causes of hyperglycemia simultaneously
primary and secondary aim of combination therapy
primary: decrease HbA1c, secondary: decrease in daily insulin dose
example of combo therapy
metformin (decrease insulin resistance in liver) + sulfonylurea (increased insulin secretion)
DM + HTN =
50% likelihood of diabetic autonomic neuropathy
incidence of periop CV instability is increased by concomitant use of ___
angiotensin-converting enzyme inhibitors or angiotensin receptor blockers
most T1DM have kidney disease by age
30
how can you assess diabetic patients for risk of difficult intubation?
praying hands, TMJ joint assessement, cervical spine mobility
percentage of T1DM that are difficult intubations
30%
keep glucose level in periop period
<180 mg/dL
hyperglycemia is associated with
hyperosmolarity, infection, poor wound healing, increased mortality
“time honored approach”
patient takes 2/3 nighttime insulin (NPH/regular) and 1/2 total morning insulin dose intermediate (NPH)
on day of surgery what should the patient do about their regular insulin?
hold AM dose of regular insulin
what should patients do with their continuous pump before surgery?
decrease overnight rate by 30% and keep at basal rate for day of surgery
if patient takes glargine and lispro/aspart daily
take 2/3 glargine dose and entire lispro/aspart night before, hold AM dose
insulin infusion
add regular insulin to NS ( 1 unit/mL)
start at 0.02 -0.1 unit/kg/hr
one unit of regular insulin should lower plasma glucose by __
25-30 mg/dL
when can patients restart their diabetic meds postop?
when resumes PO intake
how often should you measure plasma glucose levels when patient is on an infusion vs PO
infusion - q30mins-1hour
po - before surgery and after surgery
do you shut a continuous pump off for surgery?
no
