Pancreatic Hormones Antidiabetic Drugs Ch 41

Front 1

nonketotic hyperosmolar coma

Back 1

dehydration, blood glucose rises 6-20 times normal range, altered mental status develops

Front 2

How are Alpha and Beta chains of insulin linked?

Back 2

Disulfide bonds at the cysine residues

Front 3

Drugs that inhibit insulin release?

Back 3

diazoxide, phenytoin, vinblastine, and colchinine

Front 4

How does hyperglycemia cause release of insulin?

Back 4

Hyperglycemia results in increased intracellular ATP levels which close ATP-dependent potassium channels. This causes depolarization releasing voltage gated Ca2+ channels

Front 5

What insulin secretagogue drugs close the K+ ATP channel?

Back 5

sulfonylureas, meglitinides, D-phenylalanine

Front 6

Once insulin has bound to the alpha subunit a confrontational change occurs stimulating what?

Back 6

Phosphorylation of tyrosine residues on Beta sub-units causing IRS molecules to bind. Activation Phosphatidylinositol-3-kinase.

Front 7

Main transporter that regulates insulin release and glucose homeostasis?

Back 7

Glut2 found in the Beta cells of the pancreas, liver, kidney, gut

Front 8

Glucocorticoids ____ the affinity of insulin receptors for insulin; GH in excess ____ the affinity...

Back 8

Lower, Increase

Front 9

Glut 5 found in the gut and kidney function with what sugar molecule?

Back 9

fructose

Front 10

What two transporters deal with absorption of glucose into brain?

Back 10

Glut1 & Glut3

Front 11

Glut 4 is found in the muscle and adipose tissues and is responsive to what hormone?

Back 11

Insulin - mediated uptake of glucose

Front 12

Insulin effects in the liver ((5)

Back 12

1. inhibits glycogenolysis
2. inhibits conversion of FA & AA -> keto acids
3. inhibits AA -> glucose
4. promotes glucose storage
5. increases triglyceride synthesis and VLDL formation

Front 13

Insulin effect on muscle (6)

Back 13

1. increased protein synthesis
2. increase AA transport
3. increase ribosomal protein synthesis
4. increased glycogen synthesis
5. increased glucose transport
6. induced glycogen synthase and inhibits phosphorylase

Front 14

Effect on adipose tissues (4)

Back 14

1. increased TG storage
2. LPL is induced (hydrolzye TG)
3. Glucose transport into cell
4. intracellular lipase is inhibited

Front 15

Rapid acting Insulin: very low propensity to self associate in antiparallel fashion and form dimers. Is stabilized into hexamers by cresol preservative.

Back 15

Insulin lispro

Front 16

Rapid acting insulin: has inhibiting insulin self-aggregation (negatively charged aspartic acid)

Back 16

Insulin aspart

Front 17

Rapid acting insulin: may have different down pathway IRS-2 activation

Back 17

Insulin glulisine

Front 18

What structure of insulin allows for its delayed onset?

Back 18

hexameric nature- too large and bulky to cross vascular endothelium into the bloodstream. Should be given 30 min before a meal peaks 2-3 hours after injection.

Front 19

Mixed with lispro, aspart, glulisine, or regular insulin and has an onset of approximately 2-5 hours and duration of 4-12 hours...

Back 19

Neutral protamine Hagedorn (NPH) , iophane insulin

Front 20

Insulin glargine

Back 20

long acting insulin that acts as background replacement. Has 6-7 fold greater binding that native insulin to IGF-1

Front 21

Insulin detemir

Back 21

less hypoglycemia than NPH insulin. action of 1-2 hours and duration of action of more than 12 hours.

Front 22

What insulins are approved for the pump without increased risk of hypoglycemia?

Back 22

aspart, lispro, and glulisine

Front 23

Mechanism of action sulfonylurea drugs

Back 23

inhibits the efflux of potassium inons through the channel and results in depolarization (release of insulin). Also inhibits alpha-cell secretions.

Front 24

tolbutamide

Back 24

sulfonylurea

Front 25

chlorpropamide

Back 25

sulfonylurea; half life 32 hours given in morning

Front 26

Tolazamide

Back 26

Sulfonylurea; slow absorbed

Front 27

Glyburide

Back 27

Sulfonylurea; single morning dose.Contraindicated in patients with hepatic impairment or renal insufficiency.

Front 28

Gipizide

Back 28

sulfonylurea; has shortest half life (2-4 hours) should be ingested 30 min before breakfast because absorption is impaired when taken with food. Much less likely to produce hypoglycemia than glyburide. Contraindicated in patients with hepatic impairment or renal insufficiency.

Front 29

Repaglinide

Back 29

Meglitinide group; regulating potassium efflux through potassium channel. *CONTAINS NO SULFUR* Approved monotherapy or in combo with biguanides (metformin)

Front 30

Nateglinide

Back 30

D-phenylalanine derivative; closure of ATP-sensitive K+ channel. Best to regulate post prandial hyperglycemia.

Front 31

Metformin

Back 31

Biguanides; reduce hepatic glucose production through activation of enzyme AMPK. Does not depend on pancreatic beta cells. May impair the hepatic metabolism of lactic acid. impairs B12 absorption when used long term.

Front 32

Thiazolidinediones

Back 32

Tzds are ligands of PPAR-Gamma which modulate genes involved in lipid and glucose metabolism, insulin transduction, and adipocyte differentiation.

Front 33

Pioglitazone

Back 33

thiazolidinediones; has a risk of bladder cancer in high doses

Front 34

Rosiglitazone

Back 34

thiazolidinediones; rapidly absorbed and highly protein bound. *More cardiovascular risk than pioglitazone* due to fluid retention resulting as mild anemia and peripheral edema.

Front 35

Acarbose and Miglitol

Back 35

competitive inhibitors of intestinal alpha- glucosidases and reduce postmeal glucose excursions by delaying digestion and absorption of starch and disaccharides.

Front 36

colesevelam hydrochloride

Back 36

bile acid sequestrant- interruption of enterohepatic circulation and decrease in FXR activation. lowers HbA1c concentration by 0.5% and LDL cholesterol by 15%.

Front 37

Pramlintide

Back 37

synthetic analog of amylin, is an injectable antihyperglycemic agent that modulates postprandial glucose levels. *approved both DM 1 &2) lowers glucagon levels, slows gastric emptying, decreases appetite

Front 38

exenatide

Back 38

GLP-1 like *fatal adverse effect is necrotizing and hemorrhagic pancreatitis*

Front 39

Liraglutide

Back 39

GLP-1 like- interacts with GLP-1 receptor and acts to increase insulin and decrease glucagon release.

Front 40

Sitagliptin

Back 40

DPP-4 inhibitor; increase circulating levels of native GLP-1 and GIP- increases glucose mediated insulin secretion and decreasing glucagon levels

Front 41

Saxagliptin

Back 41

DPP-4 inhibitor; increase circulating levels of native GLP-1 and GIP- increases glucose mediated insulin secretion and decreasing glucagon levels

Front 42

Linagliptin

Back 42

DPP-4 inhibitor; increase circulating levels of native GLP-1 and GIP- increases glucose mediated insulin secretion and decreasing glucagon levels

Front 43

What drug that is not insulin is approved for meal time use with type I DM?

Back 43

Pramlintide (analog of amylin)