Rose: Diabetes Drugs Flashcards
What is the MOA of Metformin (Biguanides)?
Decreases hepatic glucose production by inhibiting gluconeogenesis
- inhibits enzyme activities
- reduces hepatic uptake of substrates (lactate)
How does Metformin increase insulin sensitivity, reduce lipolysis in adipocytes and reduce glucose absorption from the intestine?
Suppression of mitochondrial ETC,
Increased insulin receptor activity
Stimulation of GLUT4 transporter
What are SE of Metformin?
50% of pt DIARRHEA w/ initial high dose (gradually increase dose)
*Most serious side effect = LACTIC ACIDOSIS (magnified w/ reduced renal function)
What is Sulfonylureas?
Insulin secretagogue (Glimepiride)
*requires B islets for pt response
What is the difference between 1st and 2nd generation Sulfonylureas?
1st generation: long t ½ = problematic; Tolbutamide, Chlorproamide
2nd generation: 100x more potent w/ fewer SE; Glimepiride, Glyburide, Glipizide
What is the MOA of Sulfonylureas?
SUR1 subunit of the ATP-sensitive potassium (KATP) channel →
closed channel →
activates Ca2+ channels →
increases intracellular Ca2+ levels →
induces fusion of vesicles & insulin release
What are SE of Sulfonylureas?
Hypoglycemia
weight gain
What are the three types of recombinant insulins?
Glargine – long
Lispro – rapid
Aspart – rapid
What are SE of recombinant insulins?
Hypoglycemia (initially autonomic sx, more severe signs central), wt gain, allergic rxns (hive like wheal, systemic rare), atrophy or hypertrophy of subcutaneous fat at injection site, insulin resistance
What is the MOA of Incretin and how does it affect the body?
GLP-1 Analogs
• GLP-1 stimulates insulin & inhibits glucagon secretion
• Delays gastric emptying
• Induces satiety
What is the half life for Incretin (Exenatide) and how does this affect when you should take it??
t ½ = minutes, rapid degradation by dipeptidul peptidase-IV in endothelial cells
• Admin SC before meal
• Peak concentration in 2 hrs
What are SE of incretin?
GI issues
N/V
pancreatitis
What is the MOA of DDP-IV Inhibitors (Sitagliptin)?
Inhibit degradation of incretins (GLP-1 & GIP) by DDP-IV →
enhanced incretin activity
• Inhibits glucagon secretion
What are SE of DDP-IV Inhibitors?
Well tolerated, NOT assoc. w/ hypoglycemia or wt gain
Long term use must be assessed
Used alone or w/ metformin
What is the MOA of Metglitipides (Repaglinide, Nateglinide)?
K+ channel blocker → increased insulin secretion
*requires Beta islets for pt response
When should you take Metglitinides and how long do they last?
- Oral, take w/ meal
* Rapid onset, 5-8 hr duration
What are SE of Metglitipides?
Hypoglycemia & wt gain.
tremor, GI, dizziness
What is the MOA of alpha glucosidase inhibitors (acarbose, miglitol)?
Inhibit the hydrolyzization of carbs to monosaccharides by glucosidases
When should you take Acarbose?
Taken w/ meals, slows digestion
*Acarbarose NOT absorbed
What drug can be used w/ other oral hypoglycemis to lowe r postprandial glucose levels?
Acarbose
What is the MOA of AMylin mimetics (Pramlintide)?
binds amylin receptors> • Inhibits glucagon synthesis • Inhibits glucose synthesis in liver • Delays gastric emptying • Increases satiety
When should you take pramlinitide?
SC administration before meals
Peak concentration in 30 min, t1/2 = 50 min
Excreted by kidney
What is the MOA of Thiazolidineodiones?
PPARg (+/- PPARa) receptor agonists
- Increase synthesis & transport of GLUT transporters in muscle, adipose & liver → increase glucose uptake & utilization
- Activate insulin responsive genes in liver cells that regulate CHO & lipid metabolism
** Requires Insulin presence for action
What family to PPAR receptors belong to?
steroid receptor super family and are transcription factors
