Diabetes drugs/strategy Flashcards
Treatment strategy for DM1
insulin dependent
goal is maintain insulin levels compared to physiological levels by combining long and short acting insulin
solely dependent on insulin
Treatment strategy for DM2
early in disease course promote weight loss exercise, add metformin to decrease glucose release from liver, then prevent resistance at peripheral tissue and delay absorption, finally add insulin when pancreas fails
Pathophys of DM2
Slow progression (years) from obesity to IFG to diabetes to hyperglycemia initially, pancreas secretes more insulin to overcome resistance, but eventually pancreas fails and they need insulin too
Most important diagnostic measure in DM1
blood glucose levels
Most important diagnostic measure in DM2
hbA1C
Sulfonylureas MOA
bind K+ receptors on pancreatic beta cells, Ca2+ rushes in, depolarization and increased insulin release
Promote release of endogenous insulin- worthless in type 1
First-gen sulfonylureas?
Tolbutamide
Chlorpropamide
First-gen sulfonylurea tox?
Disulfiram-like effect
Second gen sulfonylureas?
Glyburide Glimerpiride Glipizide Repaglinide (short-give with meals) Nateglinide (short)
Second gen sulfonylureas tox?
HYPOGLYCEMIA when insulin is greater than food intake
weight gain
increased TGs and LDLs
Metformin MOA
Biguanide family
1. enhances suppression of gluconeogenesis with insulin decreasing hepatic glucose output
2. enhances glucose uptake and utilization at skeletal muscle
initial monotherapy for DM2
Metformin tox
nausea, diarrhea
LACTIC ACIDOSIS- rare but high mortality
don’t give to pt’s with renal, hepatic or heart issues
NO RISK HYPOGLY OR WEIGHT GAIN
Thiozolidenedines (TZD) MOA
increase insulin sensitivity in peripheral tissue
internalized, binds PPAR nuclear transcription regulator increasing genes for glucose and lipid metabolism
TAKES WEEKS TO HAVE EFFECT
Thiozolidenedines (TZD) Tox
Weight gain from fluid retention
CONTRAINDICATED in CHF pts
rosiglitazone pulled for MI risk
Thiozolidenedines (TZD) Drugs?
Pioglitazone- only one in use
Rosglitazone
Alpha-glucosidase inhibitors?
acarbose
miglitol
Alpha-glucosidase inhibitors MOA
Inhibit intestinal brush border alpha glucosidases
Delay (not prevent) sugar hydrolysis and glucose absorption
Which prevents blood glucose spike postprandial
Alpha-glucosidase tox
abd discomfort, flatulence, diarrhea
Management of hyperglycemia in DM2?
- weight loss/exercise
- metformin
- consider combo therapy, add sulfonylurea or glitazone
- continue to modulate and monitor
- if combo therapies no longer effective, need to start insulin
DPP4 inhibitors?
sitagliptin,
saxagliptin
DPP4 inhibitors MOA
bind and inhibit DPP4, preventing the breakdown of GLP1/GIP- which are released from duodenum following oral glucose load and promote insulin release and glucagon suppression
Exenatide/liraglutide MOA
GLP1 analog that is injected every 12 hours and is resistant to DPP4
liraglutide is longer acting
Insulin therapy principles
REPLACES complete lack of insulin in type 1 SUPPLEMENTS progressive def. in Type 2 basal to start full replacement needs basal-bolus hypoglycemia and weight gain are risks
Insulin native form/physio
natural insulin secreted as hexamer and needs 1-2 hours to be broken down to monomeric form
drugs developed by modifying AA chain for longer/shorter onset analogs
