Diabetes drugs - Konorev

Question 1

what is the diagnostic criteria of diabetes mellitus?

Answer 1

increased plasma glucose levels >125 mg/dl

Question 2

what effect do T3/T4, glucagon, epinephrine and glucocorticoids have on blood glucose levels?

Answer 2

they increase blood glucose levels

Question 3

what happens in diabetes?

Answer 3

loss of insulin or insulin responsiveness -> unopposed mobilization of glucose

Question 4

what does the insulin receptor-PI3K-Akt pathway have effects on?

Answer 4

glucose, lipid and protein metabolism, via regulation of enzyme activities or gene expression

Question 5

what does the insulin receptor-MAP kinase pathway have effects on?

Answer 5

regulation of gene transcription and cell proliferation

Question 6

what are the anabolic effects of insulin on carbohydrate metabolism?

Answer 6

promotes intracellular glucose transport and utilization

• GLUT4 translocation to the cell membrane in skeletal muscle, cardiac myocytes, and adipocytes
• activation of glycoslysis
• activation of glycogen syntheses

Question 7

how does insulin oppose catabolic effects of other hormonal systems?

Answer 7

• inhibits gluconeogenesis

- inhibits glycogenolysis

Question 8

what drugs class are:

• sulfonylureas
• meglitinides
• GLP-1 agonists
• dipeptidyl Peptidase-4 (DPP-4) inhibitors

Answer 8

insulin secretagogues

Question 9

what are the rapid-acting insulins? (3)

Answer 9

• aspart (novolog)
• lispro (humalog)
• glulisine (apidra)

Question 10

what is the one short acting insulin

Answer 10

regular insulin (Humulin, novolin)

Question 11

what is the intermediate acting insulin?

Answer 11

NPH - neutral protamine hagerdorn

Question 12

what are the two long-acting insulins?

Answer 12

• detemir (Levemir)

- glargine (Lantus)

Question 13

what is the standard delivery method for insulin?

Answer 13

subcutaneous injection using disposable needles and syringes

Question 14

what insulin delivery system has

• continuous glucose sensor
• controlling device (microchip)
• insulin pump

Answer 14

artificial/bionic pancreas

Question 15

what is a bi-hormonal bionic pancreas?

Answer 15

it delivers both insulin and glucagon

Question 16

what is the MOA of amylin?

Answer 16

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

Question 17

what is the amylin analog drug?

Answer 17

pramlintide (symlin)

Question 18

what are the endogenous factors of insulin secretion regulation? (3)

Answer 18

• glucose
• GPCR-Gs ligands (B2-adrenergic agonists, GLP-1 agonists)
• GPCR-Gi ligans (somatostatin, a2-adrenergic agonists)

Question 19

what are the drug targets of insulin?

Answer 19

• resting membrane potential and specifically K-ATP channel
• voltage-dependent (L-type) calcium channel
• GPCR-Gs/GPCR-Gi cAMP axis

Question 20

incretin mimetics activate GLP-1 receptor or boost endogenous GLP-1 levels

Answer 20

insulin secretagogues

Question 21

these drugs are a group of gastrointestinal hormones that cause a decrease in blood glucose levels

Answer 21

incretins

Question 22

this incretin is synthesized by intestinal L-cells, and promotes:

• b-cell proliferation
• insulin gene expression
• glucose-dependent insulin secretion

Answer 22

Glucagon-like peptide-1 (GLP-1)

• inhibits glucagon secretion
• also causes satiety, inhibits gastric emptying

Question 23

why is GLP-1 not an effective drug?

Answer 23

it has a very short half life (1-2 mins)

Question 24

what are the two long-acting GLP-1 receptor agonists?

Answer 24

• exenatide (Byetta)

- liraglutide (Victoza)

Question 25

what are the 4 DPP-4 inhibitors? (gliptins)

Answer 25

- sitagliptin - linagliptin - saxagliptin - alogliptin

Question 26

what is the MOA of DPP-4 inhibitors?

Answer 26

- DPP-4 is a serine protease that degrades GLP-1 and other incretins - they increase levels of GLP-1 to enhance its interactions with the cognate receptor - effects are similar to those of GLP-1 agonists

Question 27

what are the 3 first generation sulfonylurea K-ATP channel blockers?

Answer 27

- chlorpropamide - tolbutamide - tolazamide

Question 28

what are the 3 second generation sulfonylurea K-ATP channel blockers?

Answer 28

- glipized - glyburide - glimepiride

Question 29

what are the 2 non-sulfonylurea K-ATP channel blockers?

Answer 29

- nateglinide | - repaglinide

Question 30

what is the MOA of K-ATP channel blockers?

Answer 30

- they bind to sulfylurea receptor | - blocking K current through Kir6.2 inwardly rectifying potassium channel

Question 31

what is the MOA of metformin (glucophage)

Answer 31

activation of AMP-dependent protein kinase

Question 32

what are the 2 thiazolidinediones?

Answer 32

- pioglitazone (actos) | - rosiglitazone (avandia)

Question 33

what is the MOA of thiazolidinediones?

Answer 33

- ligands of peroxisome proliferator-activated receptor-gamma (PPARy) - PPARu is a nuclear receptor expressed primarily in fat, muscle, liver tissue, and endothelium

Question 34

thiazolidinediones increase the transcription of what?

Answer 34

- Glut4 in skeletal muscle - Glut4 in adipocytes - IRS1, IRS2, Pi3K

Question 35

thiazolidinediones decrease the transcription of what?

Answer 35

- PEPCK | - NF-kb, AP-1

Question 36

what are the 3 sodium-glucose cotransporter 2 inhibitors? (gliflozins)

Answer 36

- canagliflozin - dapaglifozin - empagliflozin

Question 37

what do SGLT2 inhibitors do?

Answer 37

they partially block reabsorption of glucose, so more of it is excreted

Question 38

what are the 2 a-glycosidase inhibitors?

Answer 38

- acarbose | - miglitol

Question 39

what is the MOA of a-glycosidase inhibitors?

Answer 39

- 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