anti diabetic Flashcards
what receptor does insulin bind to on the cell membrane
tyrosine kinase
no C peptide with?
C peptide is in
exogenous insulin
endogenous insulin
can prevent microvascular complications (retinopathy, neuropathy, nephropathy)
control of diabetic dyslipidemia prevents macrovascular dz
tight glycemic control
dawn hyperglycemia
somogyi phenomenon
differentiate between waning of insulin or dawn phenomenon - check glucose at 3 AM
Drugs causing hyperglycemia
1) B adrenergic blockers
2) thiazides
3) diazoxide
4) clozapine, olanzapine
5) corticosteroid
6) cyclosporine, tacrolimus, sirolimus
7) protease inhibitors
increases blood glucose
stimulates adenyl cyclase and increases cAMP levels
Used: severe hypoglycemia in DM, antidote for B blocker OD
glucagon
SX: sweating. palpitation, confusion, loss of concentration, nightmares, loss of consciousness, seizures, coma
Hypoglycemia
Causes of hypoglycemia
1) exercise
2) renal failure
3) exogenous insulin
4) insulinoma
5) sulfonylurea
6) missed meals, starvation
rapid acting insulins
onset 15-30 min
DOA 3-4 hrs
Peak 1-2 hrs
lispro
aspart
glulisine
monomers on sub Q - fast absorption
rapid breakdown to monomers - can give IV
given just prior to meals
lispro
aspart
glulisine
Use: post prandial hyperglycemia, emergency - lispro
ADR: hypoglycemia is missed meal
lispro
aspart
glulisine
short acting insulins
onset 30-60 min
DOA 5-7 hrs
Peak 2-4 hrs
regular insulin (crystalline zinc)
hexamers with zinc (zinc slows absorption)
breaks down to monomers - fast absorption
given 15-30 min before meal
combo with NPH - 2x day
regular insulin (crystalline zinc)
Used: post prandial blood sugar control and emergency!
ADR: hypoglycemia if missed meal
regular insulin (crystalline zinc)
intermediate insulin
onset 1-2 hrs
DOA 4-8 hrs
peak 10 -20 hrs
isophane/NPH (neutral protamine hagedorn)
complexed with zinc and protamine in phosphate buffer - low absorption
given with food before bedtime
combo with regular insulin 2x day
isophane/NPH (neutral protamine hagedorn)
cloudy suspension - no IV, SQ only
Use: to prevent night time blood sugar excursions, blood sugar control during day with regular insulin
ADR: hypoglycemia with fasting/ strenuous exercise
isophane/NPH (neutral protamine hagedorn)
long acting
onset 1-2 hrs
DOA -24 hrs
peak none
glargine
determir
low pH 4.0 stabilizes insulin
more weight gain
glargine
in neutral sub cut space, breaks down slowly - absorb slowly
cannot be combined with other insulins
once daily injections
glargine
determir
myristoylated and bound to albumin: slow release
determir
Uses: basal insulins and sustained action - long duration control blood sugar, night time control
ADR: no peak - less hypoglycemia
glargine
determir
ultra long acting
onset 1-2 hrs
DOA > 24 hrs
peak none
degludec
forms polymers when injected subcut
dissociates to hexamers then monomers - slow absorption
alternate day injections
degludec
Use: long duration control of blood sugar
ADR: no peak - less hypoglycemia
degludec
alpha islets
glucagon
beta islets
insulin
delta islets
somatostatin
pp islets
pancreatic polypeptide
g islets
gastrin
safest treatment for pregnancy
regular insulin
MOA: decrease hepatic gluconeogenesis
increase insulin sensitivity of target tissues - activation of GLUT4 receptors on skeletal muscle and adipocytes
increase peripheral tissue uptake of glucose
metformin
ADR: GI distress (nausea and diarrhea), lactic acidosis (renal dysfunction), vit B12 deficiency
metformin
CI: renal or liver disease, cardiac failure, chronic hypoxic lung dz, pregnancy, along with contrast media - increased risk renal failure
metformin
first line for T2DM
metformin
MOA: increase insulin sensitivity of target tissues mainly adipocytes
increase peripheral uptake of glucose
PPAR-y activates act as ligands for PPAR- y receptors
ploglitazone
rosiglitazone
ADR: weight gain, water retention, heart failure - congestive, risk of stroke, bladder cancer risk, osteoporosis
ploglitazone
rosiglitazone
CI: px with heart disease (especially rosiglitazone), liver dysfunction, pregnancy
Tx: T2DM
ploglitazone
rosiglitazone
MOA:
increases secretion of insulin by binding to SUR1 receptor on the K ATP ch on beta cells
inhibiting the K efflux
depolarization- more Ca2+ entry - fusion of insulin vesicles with cell membrane and release insulin decreased hepatic clearance of insulin
glyburide
glipizide
glimepiride
chlorpropamide, tolbutamide
all are sulfonylureas
ADR: hypoglycemia, weight gain, GI distress, pruritus, agranulocytosis, aplastic anemia
secondary failure
glyburide
glipizide
glimepiride
chlorpropamide, tolbutamide
sulfonylureas that causes SIADH and disulfiram like action
chlorpropamide
CI: pregnancy, liver dysfunction, renal failure (tolbutamide, glimepride can be given), cross allergy
sulfonylureas
sulfonylureas that CI in elderly
chlorpropamide
second line tx for T2DM
sulfonylureas
MOA: increases insulin secretion by binding to and inactivating K ATP ch on beta cells the rest act like sulfonylureas
nateglinide
repaglinide
ADR: hypoglycemia, secondary failure, drug interactions with CYP inhibitors/inducers, hepatic dysfunction
nateglinide
repaglinide
CI: pregnancy
Tx: post prandial hyperglycemia control - adjunct
give before meal
nateglinide
repaglinide
sulfonylurea given to px with increase serum creatine and heart risk
glimepiride
MOA: dipeptidyl peptidase-4 enzyme inactivates incretins
incretins stimulate release of insulin in response to elevated blood sugar levels and inhibit glucagon
inhibition of DPP4 - prolongs incretin action more circulating insulin
sitagliptin
saxagliptin
ADR: debilitating joint pain, hypoglycemia with SU/insulin
sitagliptin
saxagliptin
CI: pregnancy
Tx: adjunct T2DM
sitagliptin
saxagliptin
MOA: long acting incretin - GLP-1 analogue
prolonged incretin action - prolongs circulating insulin in response to high blood sugar
exenatide
liraglutide
dulaglutide
ADR: nausea and vomiting, hypoglycemia with SU/insulins
exenatide
liraglutide
dulaglutide
GLP-1 agonist with ADR of immunogenicity
exenatide
CI: pancreatitis, pregnancy, hypertriglyceridemia, thyroid medullary cancer, gallbladder stone
exenatide
liraglutide
dulaglutide
Tx: T2DM, obesity
SQ inj once daily
exenatide
liraglutide
dulaglutide
MOA: alpha glucosidase enzyme on brush border of apical cells in intestine
breaks down starch to simple sugars, helps absorption of sugar
inhibition of enzyme - less absorption of sugar, reduced blood sugar levels
acarbose
miglitol
ADR: flatulence, bloating, diarrhea
acarbose
miglitol
CI: pregnancy
Tx: T2DM
acarbose
miglitol
MOA: SGLT 2 on proximal renal tubules
decrease reabsorption of filtered glucose
block SGLT 2 increased excretion of glucose, decreased reabsorption of filtered glucose, low blood sugar levels
canagliflozin
dapagliflozin
empaglifozin
ADR: UTI, genital mycotic infections, ketoacidosis, acute kidney injury
canagliflozin
dapagliflozin
empaglifozin
CI: pregnancy and renal dysfunction
Tx: part of 1st line for T2DM
canagliflozin
dapagliflozin
empaglifozin
binds to amylin receptor in brain
delayed gastric emptying - satiety
decrease in glucagon release
pramlintide
ADR: nausea hypoglycemia with SU/insulin
pramlintide
CI: pancreatitis
Tx: T1DM and T2DM
SQ inj
peak with 20 min
pramlintide
