Diabetes Pharmacotherapy Flashcards
rapid acting insulin
lispro
aspart
glulisine
short acting insulin
regular - human
intermediate acting insulin
NPH
log acting insulin
glargine
detemir
fixed mix insulin
NPH/regular
metformin
biguanine
-antihyperglycemic
glimepiride
sulfonylurea
-stimulate insulin secretion
glipizide
sulfonylurea
-stimulate insulin secretion
glyburide
sulfonylurea
-stimulate insulin secretion
repaglinide
non-sulfonylurea secretagogue
-stimulate insulin secretion
nateglinide
non-sulfonylurea secretagogue
-stimulate insulin secretion
pioglitazone
insulin sensitizer
-thiazolidinediones - TZD
acarbose
alpha-glucosidase inhibitor
prevent complex carb hydrolysis and delay carb absorption
miglitol
alpha-glucosidase inhibitor
prevent complex carb hydrolysis and delay carb absorption
exenatide
GLP-1 agonist
potentiate glucose-dependent insulin secretion
suppress glucagon secretion
slow gastric emptying
promote satiety
C peptide
removed from proinsulin when insulin released
insulin chemistry
solution as monomer, dimer, hexamer
Zn coordinated
crystallize differently - determine how fast dissolve after subQ injection
stimulus for insulin release
glucose
also, AAs, FAs, ketone bodies
alpha2
inhibit insulin release
beta2
stimulate insulin release
vagus
stimulate insulin release
GLUT2
glucose transport into beta cell
ATP generation - results in influx of extracellular Ca
leading to fusion of insulin granules with membrane
-insulin release
insulin release
two phases
DMII - missing first
DMI - missing both
insulin after meal
greater frequency and higher amplitude pulses
insulin in circulation
free monomer
-half life - 5-8 minutes
insulin receptor
tyrosine kinase
GLUT4
insulin sensitive receptors
go to membrane when have increased insulin stimulation
-muscle and adipose tissue
long term insulin resistance
GLUT1 and GLUT4
diminished insulin secretion in DM II
GLUT4
phosphoinositol 3-kinase
activated insulin receptor brings GLUT4 receptors to membrane via this
DM I
lack beta cell activity - absent insulin
associated with HLA
insulin-dependent
DM II
defective insulin secretion
tissue resistance
increased hepatic glucose
with obesity
strong fam hx
therapeutic insulin subQ
1 doesn’t match normal up and down of insulin levels
2 goes to peripheral circulation, instead of portal circulation
detemir
long acting insulin - binds albumin
glargine
long acting insulin - acidic pH
lispro, aspart, glulisine
rapid acting insulin - 2AA substitution - faster than regular insulin
intermediate insulin
crystalline suspension
NPH
added protamine, Zn, phosphate buffer
intermediate acting insulin - crystalline suspension
rapid acting insulin
action - 15 minutes
taken immediately before meal
lower risk of hypoglycemia**
IV insulin
only regular, aspart, glulisine, lispro
rapid acting and regular**
IV or subQ pump
neutral protamine hagedorn
NPH insulin - intermediate acting
complex with protamine and zinc
changes in subQ blood flow
important indicator in variability of response to insulin
exubera
inhalation insulin
CSII
continuous subQ insulin infusion
timed throughout day
-regular or rapid acting
measure of long term hyperglycemic control
HbA1C < 6.5%
IIT
intensive insulin therapy
basal - long acting QD
bolus - rapid acting before meal
split mix insulin therapy
mix dose of NPH/regular insulin
adverse effect insulin
hypoglycemia
more rigorous attempt to achieve euglycemia - greater risk hypoglycemia
counter-regulatory hormones
epi, glucagon, cortisol, GH
dominant - glucagon
type I DM - long duration - glucagon secretion becomes deficient and epi becomes dominant
tx of hypoglycemia
ingestion glucose
severe - glucagon injection or IV glucose
lipoatrophy and lipohypertrophy
subQ fat at site of insulin injection
patient advised to rotate injection site
DKA tx
IV insulin continuous infusion
also - replacement of fluid and electrolytes
perioperative and childbirth
when diabetic patient gets IV insulin - more control
drug-induced hypoglycemic state
ethanol
beta antagonist
salicylates
ethanol - inhibitor of gluconeogenesis
inhibit insulin secretion
phenytoin
clonidine
CCBs
inhibit insulin secretion
diuretics
hyperglycemic effect
epi
glucocorticoid
contraceptives
initial therapy for DMII patient who fails diet and exercise therapy
metformin
DM I tx
insulin
-don’t respond to oral hypoglycemic agents
metformin effect
antihyperglycemic effect
does not cause hypoglycemia**
- inhibits gluconeogenesis
- increased insulin action
- increased glucose uptake
- reduces intestinal glucose absorption
obese insulin resistant pt with DM II tx
metformin**
also has lipid lowering effect
lipid lowering effect
metformin
sulfonylurea MOA
stimulate insulin release from beta cells of pancreas
-bind and block ATP sensitive K channel - causes Ca influx - insulin release**
extrapancreatic effects
sulfonylureas
- increased insulin receptors
- increased glucose transporters
- enhanced tissue response to insulin
second generation sulfonylureas
100x more potent
pt older than 30, not obese, residual beta cell fxn, fasting glucose <300
sulfonylurea tx
adverse sulfonylurea
hypoglycemia - including coma
CI - sulfa allergy, DMI, pregnant/nursing mother, hepatic/renal insufficiency
meglitinide MOA
bind ATP sensitive K channels - different site than sulfonylureas
opens Ca channels - rapid increase in insulin release
rapid acting - meal skipped - so is drug dose**
alpha glucosidase inhibitors
competitive inhibition of sugar digestion
-limits postprandial rise in glucose
for new DM II pt with mild hyperglycemia
adverse of alpha glucosidase inhibitors
flatulence, diarrhea, GI upset
TZDs
insulin sensitizers
-removed from market
bind nuclear transcription factors involving insulin receptor signaling cascade
resensitize target tissue to insulin
increase GLUT 1 and 4 transport proteins
rosiglitazone
risk of MI
TZD
GLP-1 analogs
secreted by intestinal L cells
agonist at GLP-1 receptor
exenatide
GLP-1
reduction of HbA1c levels
need for BID subQ injections
