Rose: Diabetes Drugs

Question 1

What is the MOA of Metformin (Biguanides)?

Answer 1

Decreases hepatic glucose production by inhibiting gluconeogenesis

• inhibits enzyme activities
• reduces hepatic uptake of substrates (lactate)

Question 2

How does Metformin increase insulin sensitivity, reduce lipolysis in adipocytes and reduce glucose absorption from the intestine?

Answer 2

Suppression of mitochondrial ETC,

Increased insulin receptor activity

Stimulation of GLUT4 transporter

Question 3

What are SE of Metformin?

Answer 3

50% of pt DIARRHEA w/ initial high dose (gradually increase dose)

*Most serious side effect = LACTIC ACIDOSIS (magnified w/ reduced renal function)

Question 4

What is Sulfonylureas?

Answer 4

Insulin secretagogue (Glimepiride)

*requires B islets for pt response

Question 5

What is the difference between 1st and 2nd generation Sulfonylureas?

Answer 5

1st generation: long t ½ = problematic; Tolbutamide, Chlorproamide

2nd generation: 100x more potent w/ fewer SE; Glimepiride, Glyburide, Glipizide

Question 6

What is the MOA of Sulfonylureas?

Answer 6

SUR1 subunit of the ATP-sensitive potassium (KATP) channel →
closed channel →
activates Ca2+ channels →
increases intracellular Ca2+ levels →
induces fusion of vesicles & insulin release

Question 7

What are SE of Sulfonylureas?

Answer 7

Hypoglycemia

weight gain

Question 8

What are the three types of recombinant insulins?

Answer 8

Glargine – long
Lispro – rapid
Aspart – rapid

Question 9

What are SE of recombinant insulins?

Answer 9

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

Question 10

What is the MOA of Incretin and how does it affect the body?

Answer 10

GLP-1 Analogs
• GLP-1 stimulates insulin & inhibits glucagon secretion
• Delays gastric emptying
• Induces satiety

Question 11

What is the half life for Incretin (Exenatide) and how does this affect when you should take it??

Answer 11

t ½ = minutes, rapid degradation by dipeptidul peptidase-IV in endothelial cells
• Admin SC before meal
• Peak concentration in 2 hrs

Question 12

What are SE of incretin?

Answer 12

GI issues
N/V
pancreatitis

Question 13

What is the MOA of DDP-IV Inhibitors (Sitagliptin)?

Answer 13

Inhibit degradation of incretins (GLP-1 & GIP) by DDP-IV →
enhanced incretin activity
• Inhibits glucagon secretion

Question 14

What are SE of DDP-IV Inhibitors?

Answer 14

Well tolerated, NOT assoc. w/ hypoglycemia or wt gain
Long term use must be assessed

Used alone or w/ metformin

Question 15

What is the MOA of Metglitipides (Repaglinide, Nateglinide)?

Answer 15

K+ channel blocker → increased insulin secretion

*requires Beta islets for pt response

Question 16

When should you take Metglitinides and how long do they last?

Answer 16

• Oral, take w/ meal

* Rapid onset, 5-8 hr duration

Question 17

What are SE of Metglitipides?

Answer 17

Hypoglycemia & wt gain.

tremor, GI, dizziness

Question 18

What is the MOA of alpha glucosidase inhibitors (acarbose, miglitol)?

Answer 18

Inhibit the hydrolyzization of carbs to monosaccharides by glucosidases

Question 19

When should you take Acarbose?

Answer 19

Taken w/ meals, slows digestion

*Acarbarose NOT absorbed

Question 20

What drug can be used w/ other oral hypoglycemis to lowe r postprandial glucose levels?

Answer 20

Acarbose

Question 21

What is the MOA of AMylin mimetics (Pramlintide)?

Answer 21

binds amylin receptors>
• Inhibits glucagon synthesis
• Inhibits glucose synthesis in liver
• Delays gastric emptying
• Increases satiety

Question 22

When should you take pramlinitide?

Answer 22

SC administration before meals

Peak concentration in 30 min, t1/2 = 50 min

Excreted by kidney

Question 23

What is the MOA of Thiazolidineodiones?

Answer 23

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

Question 24

What family to PPAR receptors belong to?

Answer 24

steroid receptor super family and are transcription factors