Endocrine: Drugs for Diabetes

Question 1

Which cell receptor does insulin activate to cause cell growth, proliferation, and gene expression?

Answer 1

MAP kinase

Question 2

Which cell receptor does insulin activate to cause increased GLUT4 expression and synthesis of lipids, proteins, and glycogen?

Answer 2

PI-3K

Question 3

How does insulin decrease glucose in the blood? (5)

Answer 3

GLUT4 translocation in skeletal/cardiac muscle and adipocytes
Activation of glycolysis
Activation of glycogen synthesis

Inhibition of gluconeogenesis
Inhibition of glycogenolysis

Question 4

What are the rapid acting insulins?

Answer 4

Lispro
Aspart
Glulisine

Question 5

What are the short acting insulins?

Answer 5

Regular insulin

Question 6

Which are the intermediate acting insulins?

Answer 6

NPH insulin

-not used much anymore

Question 7

What are the longer acting insulins?

Answer 7

Detemir

Glargine
-longest acting

Question 8

Clinical use of lispro, aspart, or glulisine?

Answer 8

Decrease the post prandial hyperglycemia seen after meals

Question 9

Which insulin is used for IV?

Answer 9

Regular insulin

-can use in emergency situations like DKA, HHS, or hyperkalemia

Question 10

So say you wanted to cover someone with diabetes both after meals and all day, which combo of insulins would be best?

Answer 10

A rapid acting + a long

So: lispro, aspart, or glulisine + detemir/glargine

Question 11

What are some adverse effects of insulin?

Answer 11

Hypoglycemia, lipodystrophy
Weight gain
Resistance
Hypokalemia

Question 12

MOA of pramlintide? (3)

Answer 12

Amylin analog

• blocks glucagon secretion
• slows gastric emptying
• increases satiety

Question 13

What type of DM does pramlintide treat?

Answer 13

Type 1 or 2

The rest, besides insulin, only treat type 2

Question 14

What are the adverse effects of pramlintide?

Answer 14

Nausea, vomiting, diarrhea

Severe hypoglycemia if used with insulin

Question 15

MOA of Exenatide or Liraglutide?

Answer 15

GLP-1 agonists

-activates Gs, increases cAMP and PKA, which causes exocytosis of insulin

Question 16

Adverse effects of the GLP-1 agonists (exenatide and liraglutide)

Answer 16

N/V, diarrhea, anorexia

Hypoglycemia

Question 17

What is the suffix of all the DPP-4 inhibitors

Answer 17

Gliptin!

Sitagliptin, linagliptin, saxagliptin, alogliptin

Question 18

MOA of the DPP-4 inhibitors (gliptins)

Answer 18

Decrease breakdown of GLP-1

-ultimately increases insulin release

Question 19

Adverse effects of the DPP-4 inhibitors?

Answer 19

Hypoglycemia

Question 20

What is the MOA of Sulfonylureas/meglitinides?

Answer 20

block K-ATPase channels (via SUR1), Ca++ rushes in and Insulin is released

Question 21

What are the first gen sulfonyureas

Answer 21

Amides

Chlorpropamide, tolbutamide, tolazamide

Question 22

What are the second generation sulfonylureas?

Answer 22

Glipizide
Glyburide
Glimepiride

Question 23

What are the meglitinides?

Answer 23

Nateglinide
Repaglinide

-glinides

Question 24

What are the adverse effects of the sulfonyureas/meglitinides?

Answer 24

Hypoglycemia
Weight gain
Secondary failure

Question 25

What drugs can enhance the effect of sulfonylureas?

Answer 25

sulfonamides, clofibrates, aspirin/NSAIDs Ethanol CYP inhibitors: azoles, gemfibrozil. cimetidine

Question 26

What drugs can decrease the glucose lowering effect of sulfonylureas?

Answer 26

Drugs that inhibit insulin secretion: B-blockers, CCBs CYP inducers: phenytoin, griseofluvin, rifampin

Question 27

Clinical use for the meglitinides?

Answer 27

Control of postprandial hyperglycemia in T2DM | -shorter acting than the sulfonylureas

Question 28

MOA of metformin?

Answer 28

activation of AMP kinase | -decreases gluconeogenesis, increases insulin sensitivity

Question 29

Which diabetic agent is usually first line in those w T2DM?

Answer 29

Metformin - no real issue w hypoglycemia - promotes weight loss - taken orally (instead of injection) - Can be combined

Question 30

How is metformin excreted?

Answer 30

Unmetabolized | -watch in those w renal failure!!

Question 31

Adverse effects of metformin?

Answer 31

GI upset Lactic acidosis

Question 32

What conditions is metformin contraindicated in?

Answer 32

Renal or liver issues

Question 33

What are the thiazolidinediones (TZDs)?

Answer 33

-glitazones Pioglitazone Rosiglitazone

Question 34

MOA of the TZDs?

Answer 34

ligands for PPARy | -increase adiponectin and GLUT4

Question 35

Whare TZDs safe for those with renal issues?

Answer 35

Yes

Question 36

Adverse effects of TZDs?

Answer 36

Weight gain Edema -increases ENaC channels Exacerbate HF -increased water retention Osteoporosis -suppress osteoblasts

Question 37

MOA of canagliflozin, dapagliflozin, empagliflozin?

Answer 37

SGLT2 inhibitors | -work at PCT to block reabsorption of glucose

Question 38

Adverse effects of the SGLT2 inhibitors (flozins)

Answer 38

Osmotic Diuresis and Orthostatics | Genital and UTIs (candidiasis)

Question 39

Benefitial effects of SGLT2 inhibitors?

Answer 39

Reduces plasma uric acid levels Weight loss improves overall cardiovascular and renal outcomes

Question 40

MOA of acarbose and Miglitol?

Answer 40

competitive inhibition of a-glycosidases | -block resorption of disaccharides in intestines

Question 41

Effect of acarbose and miglitol on glucose levels?

Answer 41

Lower postprandial hyperglycemia to create insulin sparing effect

Question 42

Adverse effects of acarbose and miglitol?

Answer 42

GI Upset: malabsorption and flatulence