Exam 1 - oral diabetic agents Flashcards
Sulfonylureas
1: tolbutamide*, tolazamide, chlorpropamide
2: glyburide, glipizide, glimeperide
why are 2nd generation sulfonylureas better than 1st generation?
- less side effects
- less protein binding & drug interactions
- more potent
why use tolbutamide if using 1st generation sulfonylureas?
- shortest duration of effect (6-12 hours)
- SE gone faster than others
DOA of chlorpropamide & 2nd generations
chlorpropamide - more than 46 hours
2nd generation - 12-24 hours
MOA of sulfonylureas?
- bind receptor to increase insulin secretion
- increase insulin sensitivity
- decrease hepatic glucose production
ADRs of sulfonylureas?
- severe hypoglycemia
- weight gain (2-12 lbs)
- anemia
- sun sensitivity, itch, rash
- disulfiram (chloropropamide & tolbutamide)
- metallic taste
- GI (N, V, dyspepsia)
contraindications of sulfonylureas?
- advanced kidney or liver disease
- T1DM
- pregnancy
- sulfa-allergy
problem with long term use of sulfonylureas? causes?
secondary failure due to:
- decreased beta cells
- decreased physical activity
- increased fat
meglitinides
nateglinide* (less hypoglycemia)
repaglinide
moa of meglitinides
bind receptor to increase insulin secretion during/after meals
peak of meglitinides? when to take meglitinides?
peak at 1 hour
take 30 minutes prior to meal
ADRs of meglitinides
hypoglycemia
weight gain
URI
MOA of metformin
increases #/affinity of insulin receptors in periphery:
- decrease hepatic glucose production
- decreases glucose uptake in gut
- increase glucose uptake
Definition of euglycemic? Two euglycemic drugs?
Decreases high sugar without causing low sugar: No hypoglycemia!
Metformin &
High AM sugars?
metformin inhibits gluconeogenesis of liver at night and will reduce AM sugars
side effect of metformin inhibiting gluconeogenesis?
decrease ability to metabolize lactic acid
Drugs that do not cause weight gain?
metformin
ADRs of metformin
- B12 deficiency
- lactic acidosis
- GI (N, V, D, bloating, flatuence)
what to do when giving radio contrast dye while pt is on meformin?
stop 1 day before and hold until 2 days after
contraindications of metformin
- hepatic insufficiency
- SCr greater than 1.5 (M) and 1.4 (F)
- CrCl less than 30
- over 80 (check renal fxn)
- tissue hypoxia prone (old or CVD)
- ETOH (increase hypoglycemia)
when to use metformin?
- pre - diabetes
- overweight T2DM
benefits of metformin?
decrease macrovascular events (MI & CVA)
examples of thiazolidinediones
- pioglitazone
- rosiglitazone
MOA of thiazolidinediones
Bind fat cells to increase adiponectin & decrease resisting:
- increase insulin sensitivity
ADRs of thiazolidinediones
- hepatotoxicity (BL LFTs) *
- heart failure (BBW) *
- hypoglycemia with other drugs
- anemia & low WBC (first 4-8 weeks)
- increase HDL, decrease LDL and TG
- fluid retention (increase weight and edema) *
- bladder cancer (pioglitazone)
- bone fractures (no osteoporosis pt)
contraindications of thiazolidindiones
- hepatic impairment
- pregnancy
- fluid retention
- class 3 or 4 HF
alpha-glucodiase inhibitors
- acarbose
- miglitol
MOA of alpha-glucodiase inhibitors
inhibit digestion/absorption of starches and sucrose
ADRs
- GI (gas, D, pain)
- hypoglycemia with other SUs
contraindications
- colonic ulcers
- inflammatory bowel
- renal failure
- partial obstruction
DDP-4
- sitagliptin
- saxagliptin
- linagliptin
- alogliptin
MOA DDP-4
inhibit breakdown of GLP-1
- decreases glucagon
- slows gastric emptying
- increases satiety
- increases insulin release
ADRs DDP-4
- hypoglycemia with SUs
- URIs
- UTIs
- HA
- sitagliptin: pacreastitis, angioedema, SJS, anaphylaxis
contraindications of DDP-4
pancreatitis
hypersensitivity rxn
MOA of GLP-1 analogs
bind GLP-1 receptor
- decrease glucagon
- increase satiety
- slow gastric emptying
- increase insulin secretion
GLP-1 analogs
linaglutide
duraglutide
exenatide
how to administer GLP-1 analogs
inject 1 hour before meal (as an adjunct to SU or metformin)
ADRs of GLP-1 analogs
- hypoglycemia with SUs
- GI: N, V, GERD (up to 4 weeks)
contraindications of GLP-1 analogs
- GI disorders (gastroparesis)
- CrCl
sodium glucose cotransporter 2
- canagliflozin (w/ metformin)
- dapagliflozin (w/ metformin)
- empagliflozin (w/ linagliptin)
MOA of SGLT2
block/delay reabsorption of glucose in PCT
ADRs of SGLT2
- UTIs
- yeast infections
- polyuria
contraindications SGLT2
CrCl
amylin MOA
slows the rate of BG rise
- decreasing glucagon
- increasing satiety (targets brain)
- slows gastric emptying
- *decreases hepatic output of glucose
amylin
pramlinitide
ADRs
- hypoglycemia (BBW)
- GI: N, V, anorexia
- HA
(2-3 go away in 1st month)
contraindications
- gastroparesis
- BG noncompliance
- hypoglycemia unaware/freq.
- A1C >9%
Goals for T2DM
- A1c less than 7
- FPG 70-130
- 1 hour postprandial 180
- 2 hour postprandial 150
- BP less than 140/80
- LDL less than 100 (CVD less than 80)
- TG less than 150
drugs than only lower A1C by 0.5%
nateglinide
acarbose
miglitol
drugs that cause weight gain
SUs, meglinides, thiazoldinediones
drugs that don’t cause weight gain
metformin, alpha-glucosease inhibitors, GLP-1
