Drugs Used in Diabetes

Question 1

Diagnosing criteria for DM =

Answer 1

Fasting glucose > 125 mg/dl

Question 2

What increases blood glucose? (4)

Decreases? (1)

Answer 2

Thyroid hormones
Glucagon
Epinephrine
Glucocorticoids

Insulin

Question 3

Which 2 insulin pathways lower blood glucose levels?

Answer 3

1. Insulin Receptor-PI3K-Akt pathway: effects on glucose, lipid and protein metabolism. Loads GLUT4 onto membrane for glucose uptake.
2. Insulin Receptor-MAP kinase pathway: regulation of gene transcription and cell proliferation.

Question 4

Which cell-types does GLUT4 exist on? (3)

What processes does it activate? (2)
What processes does it inhibit? (2)

Answer 4

Skeletal muscle, cardiac myocytes, and adipocytes

+ glycolysis and + glycogen synthesis

• GNG and - glycogenolysis

Question 5

Rapid-acting insulins (3)

Short-acting insulins (1)

Intermediate-acting insulins (aka neutral protamine Hagerdorn (NPH)) (1)

Long-acting insulins (2)

Answer 5

Aspart, Lispro, Glulisine

Regular insulin

NPH

Detemir, Glargine

Question 6

What are 4 manners of insulin delivery?

Answer 6

Standard delivery - subQ injection using disposable needles/syringes

Portable pen injectors

Continuous subQ insulin infusion devices (insulin pumps)

Artifical or bionic pancreas

• continuous glucose sensor
• micorchip
• insulin pump
• bihormonal bionic pancreas (insulin and glucagon)

Question 7

What is Amylin?

What is the MOA? (4)

What is the drug name?

Answer 7

A pancreatic hormone synthesized by beta cells.

Inhibits glucagon secretion
Enhances insulin sensitivity
Decreases gastric emptying
Satiety

Pramlintide

Question 8

What are incretins?

What is the major one?
What does it promote? (3)
What does it inhibit? (2)

What is the half-life?

Answer 8

GI hormones that decrease blood glucose levels.

GLP-1
Promotes beta cell proliferation, insulin gene expression, glucose-dependent insulin secretion
Inhibits glucagon secretion and gastric emptying (causes satiety)

Very short half-life (1-2 min) - not an effective drug

Question 9

What are the 2 insulin mimetics?

Answer 9

Long-acting GLP-1 receptor agonists

DPP-4 inhibitors (dipeptidyl peptidase-4)

Question 10

2 long-acting GLP-1 receptor agonists

Answer 10

Exenatide

Liraglutide

Question 11

4 DPP-4 inhibitors

MOA (2)

Answer 11

Sitagliptin
Linagliptin
Saxagliptin
Alogliptin
"gliptins"

Increase levels of GLP-1 to enhance its interactions with its cognate receptor.
-effects similar to GLP-1 agonists

Question 12

What are Sulfonureas?

First-gen (3)

Second-gen (3)

Non-sulfonureas (meglitinides) (2)

Answer 12

K-ATP blockers

1st: Chloropropamide, Tolbutamide, Tolazamide
2nd: Glipizide, Glyburide, Glimepiride

Non-sulfonureas: Nateglinide, Repaglinide

Question 13

What is the MOA of Sulfonureas?

Answer 13

K-ATP blockers

They bind SUR and block K+ current through Kir6.2 inwardly rectifying K+ channel.

Question 14

What is the major Biguanide?

MOA

Answer 14

Metformin

Activates AMP-dependent protein kinase

Question 15

What are the 2 Thiazolidinediones?

MOA

Answer 15

Pioglitazone
Rosiglitazone

They are ligands of PPAR-y, which is a nuclear receptor expressed in fat, muscle, liver tissue and endothelium. It upregulates GLUT4 receptors.

Question 16

Sodium-Glucose co-transporter 2 (SGLT2) inhibitors (Gliflozins) (3)

MOA

Answer 16

Canagliflozin
Dapagliflozin
Empagliflozin

Increases filtration and partial reabsorption of glucose

Question 17

a-Glycosidase inhibitors (2)

MOA

What is a unique effect?

Answer 17

Acarbose
Miglitol

Competitively inhibits a-glycosidases (lowers absorption of starches and disaccharides).

Lowers postprandial hyperglycemia to create an insulin-sparing effect.

Question 18

Which 2 types of drugs are used only in T1DM?

Answer 18

Insulin and Amylin analogues (can also be used for T2DM)

Question 19

What are ligands of GPCR-Gs? (2)

Answer 19

B2-AR agonists

GLP-1 agonists (incretins)

Question 20

What are ligands of GPCR-Gi? (2)

Answer 20

a2-AR agonists

Somatostatin