Konorev: Drugs for Diabetes

Question 1

What is Diabetes mellitus?

Answer 1

a group of common metabolic disorders resulting in hyperglycemia

• deficiency of insulin
• inability of body to respond to insulin
• increased level of counter-regulatory hormones that oppose insulin action

Question 2

Diagnostic criteria for DM?

Answer 2

-increased plasma glucose levels

Question 3

Type 1 DM

Answer 3

-insulin dependent

Question 4

Type 2 DM

Answer 4

-no insulin dependent

Question 5

What does insulin normally do?

Answer 5

lowers blood glucose

Question 6

What are things that raise blood glucose levels?

Answer 6

• T3/4
• Glucagon
• Epinephrine
• Glucocorticoids

Question 7

What is insulin’s effect on plasma K+ levels?

Answer 7

decreases them
-when ATP is generated in the cell due to glucose metabolism after insulin lets it in, that ATP blocks the K+ efflux channel

Question 8

What does PKA do?

Answer 8

• generated after GPCR=Gs ligands are activated (B2-AR agonists or GLP-1 receptor agonists)
• it opens up the Ca2+ channel so that can rush in and promote the exocytosis of insulin

Question 9

What opposes the creation of PKA?

Answer 9

• GPCR-Gi ligands:
• Somatostatin
• alpha2-AR agonists

Question 10

What is the VDCC

Answer 10

-L-type Ca2+ channel

Question 11

What drugs are used in diabetes?

Answer 11

• insulins
• amylin analog
• insulin secretagogues
• Biguanides
• Thiazolidinediones
• Sodium-glucose co-transporter 2 (SGLT2) inhibitors
• Inhibitors of a-glycosidases

Question 12

What are the insulin secretagogues?

Answer 12

• Sulfonylureas
• Meglitinides
• GLP-1 agonists
• Dipeptidyl Peptidase-4 (DPP-4) inhibitors

Question 13

what is most important when treating Diabetes?

Answer 13

tight glycemic control

Question 14

Rapid acting insulins (3)

Answer 14

• Aspart
• Lispro
• Gluisine

Question 15

Short acting insulin

Answer 15

-regular insulin

Question 16

Intermediate acting insulin

Answer 16

NPH: neutral Protamine Hagerdorn

Question 17

Long acting insulin

Answer 17

• Detemir

- Glargine

Question 18

Standard delivery of insulins

Answer 18

Subcutaneous injection using disposable nedles and syringes

Question 19

What is that really cool new technology thing he talked about?

Answer 19

• a bi hormonal bionic pancreas
• secretes insulin and glucagon
• registers HR

Question 20

What is Amylin?

Answer 20

a pancreatic hormone synthesized by B-cells

Question 21

MOA of amylin

Answer 21

• inhibits glucagon secretion
• enhances insulin sensitivity
• decreased gastric emptying (slows the rate of intestinal glucose absorption)
• causes satiety

Question 22

What does satiety mean?

Answer 22

feeling full

Question 23

What is the amylin analog drug?

Answer 23

Pramlintide

-these amylins are usd with insulin to control postprandial hyperglycemia

Question 24

What are the Incretins?

Answer 24

a group of FI hormones that stimulate a decrease in blood glucose levels
-Glucagon-like peptide-1 (GLP-1)

Question 25

What is GLP-1?

Answer 25

- synthesized by intestinal L-cells - promotes: B cell proliferation, insulin gene expression, glucose-dependent insulin secretion - inhibits glucagon secretion - also causes satiety, inhibits gastric emptying

Question 26

What is the one thing that's wrong with GLP-1?

Answer 26

it has a very short half-life - 1-2 minutes - not an effective drug

Question 27

What are the incretin mimetics?

Answer 27

- long-acting GLP-1 receptor agonists - Dipeptidyl peptidase-4 (DPP-4) inhibitors - remember, it stimulates insulin release and inhibits glucagon release - does a great job of lowering blood glucose

Question 28

Long-acting GLP-1 receptor agonists

Answer 28

- Exenatide | - Liraglutide

Question 29

What does the GLP-1 receptor agonists do? MOA?

Answer 29

- Gs protein receptor - makes PKA.... upregulates insulin gene transcription and potentiates the Ca2+ influx so we can secrete it - Glucose enters cell and makes ATP... blocks K+ efflux channels

Question 30

DPP-4 inhibitors

Answer 30

- Sitagliptin - Linagliptin - Saxagliptin - Alogliptin

Question 31

MOA of DPP-4 inhibitors

Answer 31

- they stop DPP-4 which is a serine protease that degrades GLP-1 and other incretins - keeps that good GLP-1 intact

Question 32

What are the K(ATP) channel blockers?

Answer 32

Sulfonylureas: first and second gen | Non-sulfonylureas(meglitinides)

Question 33

Sulfonylureas

Answer 33

- First Gen: Chlorpropamide, Tolbutamide, Tolazamide | - Second gen: Glipizide, Glyburide, Glimepiride

Question 34

non- sulfonylureas (meglitinides)

Answer 34

- Nateglinide | - Repaglinide

Question 35

MOA of Katp channel blockers

Answer 35

- Bind to SUR- sulfonylurea receptor | - blocking K+ current through Kir6.2, inwardly rectifying potassium channel

Question 36

Biguanides

Answer 36

Metformin

Question 37

MOA of metformin

Answer 37

- Activation of AMP-dependent Protein Kinase - but then it shows metformin blocking a mitochondria - decreases glucoeogenesis - decreases glucose and insulin if elevated

Question 38

Thiazolidinediones

Answer 38

- Pioglitazone | - Tosiglitazone

Question 39

Thiazolidinediones MOA

Answer 39

- ligands of peroxisome proliferator-activated receptor-gamma (PPARg) - PPARg is a nuclear receptor expressed primarily in fat, muscle, liver tissue, and endothelium - inhibits NFKB, AP-1, and STAT

Question 40

What are the Sodium-glucose co transporter 2 inhibitors (Gliflozins)?

Answer 40

- Canagliflozin - Dapagliglozin - Empagliglozin

Question 41

What does SGLT2 do?

Answer 41

- normally, it lets glucose get completely reabsorbed in the kidney - now, we can excrete some of it in the urine which is nice if you're diabetic

Question 42

Alpha glycosidase inhibitors

Answer 42

- Acarbose | - Miglitol

Question 43

MOA of alpha glycosidase inhibitors

Answer 43

- only monosaccharides are absorbed from GI into the blood - competitive inhibition of a-glycosidases, a family of enzymes on the intestinal epithelium defer digestion and thus absorption of ingested starch and disaccharides - lower postprandial hyperglycemia to create an insulin-sparing effect