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Flashcards in Antidiabetics II Deck (58)
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1

Insulin Secretagogues

Sulfonylureas & Meglitinides

2

Sulfonylureas are effective at reducing ___ and ___

Sulfonylureas are effective at reducing fasting plasma glucose and HbA1C

3

Sulfonylureas bind to ____ subunit and block the ATP-sensitive ___ channel in the B cell membrane stimulating ___ release 

Sulfonylureas bind to SUR1 subunit and block the ATP-sensitive K+ channel in the B cell membrane stimulating insulin release 

 

4

sulfonylureas end in "__"

"ide" 

5

1st generation Sulfonylurea

 

Chlorpropamide

6

Chlorpropamide has a ___ half life 

AE's? 

  • Long half-life
  • Hypoglycemia, particularly in elderly
    • Contraindicated in elderly patients
  • Hyperemic flush with alcohol
    • d/t inhibition of aldehyde dehydrogenase
  • may potentiate vasopressin
    • elicit an apparent SIADH 
    • ​hyponatremia

7

list 2nd generation Sulfonylureas

compare them to Chlorpropamide 

  • Glyburide (Glibenclamide)
  • Glipizide
  • Glimepiride
  • much more potent than 1st gen drugs
  • lack some of the adverse effects and drug interactions of 1st gen drugs
  • replaced 1st gen drugs

8

compare hypoglycemic actions between 2nd gen sulfonylureas

Glimepiride < Glipizide

 

9

Sulfonylurea & Meglitinide AEs

  • Hypoglycemia
  • Weight gain

10

list Meglitinides

Glinides have the same MOA as ___ 

  • Repaglinide, Nateglinide
  • same MOA as Sulfonylureas
    • stimulate insulin release by binding to SUR1 and inhibiting ATP-sensitive K+ channel

11

Sulfonylureas vs. Meglitinides

- effect

- onset and duration of action 

Sulfonylureas = more effective in reducing FPG and HbA1C levels

Meglitinides = more rapid onset and shorter DOA 

12

Glinides are ____ glucose regulators.

Must be taken ____; if the meal is missed the drug must be omitted

Glinides are postprandial glucose regulators

Must be taken before each meal; if the meal is missed the drug must be omitted

13

Comparing the Meglitinides, ___ has a less risk of hypoglycemia than ___

Comparing the Meglitinides, Nateglinide has a less risk of hypoglycemia than Repaglinide

14

Biguanides

Metformin

15

Metformin does not cause ____ 

does not cause ___ (even in large doses) 

___ efficacy to sulfonylureas in reducing FPG and HbA1C levels

Metformin does not cause insulin secretion 

does not cause hypoglycemia (even in large doses) 

Equal efficacy to sulfonylureas in reducing FPG and HbA1C levels

16

Metformin reduces glucose levels primarily by inhibiting ___ by reducing ____ of gluconeogenic enzymes

 

Metformin reduces glucose levels primarily by inhibiting gluconeogenesis by reducing gene expression of gluconeogenic enzymes

  • increases insulin-mediated glucose utilization in muscle and liver
  • As a result of the improvement in glycemic control, serum insulin concentrations decline slightly

17

Metformin actions are mediated by activation of ____ 

Metformin actions are mediated by activation of AMPK 

18

other effects of metformin 

  • Reduces plasma TG by 15-20%
  • weight LOSS

(sulfonylureas / glinides = weight gain)

19

1st line agent for treating T2 DM

Metformin

  • high insulin sensitivity
  • associated w/ weight loss
  • rarely causes hypoglycemia
  • does not depend on B-cells 

20

Metformin AE and contraindications

  • Largely GI: anorexia, nausea, vomiting, abdominal discomfort, diarrhea
  • Long term use: B12 deficiency
  • Fatal lactic acidosis
  • Contraindicated: renal disease, hepatic disease, hypoxia, alcoholism

21

list the TZDs

  • Pioglitazone
  • Rosiglitazone

22

Pioglitazone and Rosiglitazone decrease insulin ____ 

 ___ agonist found in muscle, fat and liver

Pioglitazone and Rosiglitazone decrease insulin resistance

Peroxisome proliferator-activated receptor-y (PPAR-y) agonist found in muscle, fat and liver

23

Glitazones promote glucose uptake and utilization in adipose tissue by ___

__ effective than Sulfonylureas/Metformin in decreasing FPG and HbA1C

MOA involves ___ 

Glitazones promote glucose uptake and utilization in adipose tissue by increasing insulin sensitization 

Less effective than Sulfonylureas/Metformin in decreasing FPG and HbA1C

MOA involves gene regulation

24

Glitazones have a slow onset and offset of activity taking ____

Glitazones have a slow onset and offset of activity taking weeks to months

25

____ effects on lipids are more favourable than ___

associated with significant improvements in:

 

pioglitazone effects on lipids are more favourable than  rosiglitazone

pioglitazone is associated with significant improvements in: HDL, TG, LDL particle concentration, LDL particle size

26

TZD AE's

  • fluid retention, weight gain, edema
  • cause or exacerbate CHF
  • contraindicated: Class III or IV heart failure
  • Troglitazone: 1st TZD approved, caused severe hepatotoxicity → withdrawn
    • FDA requires monitoring of liver function with TZD
    • so far pioglitazone or rosiglitazone have not been associated with hepatotoxicity

27

a-Glucosidase Inhibitors

Acarbose

28

Acarbose: MOA

  • competitive inhibitor of intestinal a-glucosidases
  • reduces postprandial digestion of starch and disaccharides
  • minimizes upper intestinal carb absorption and defers absorption to distal SI
    • decreases postprandial hyperglycemia and hyperinsulinemia
  • modest drop in HbA1C and FPG levels

29

Acarbose AEs

  • Flatulence, diarrhea, abdominal pain
  • Contraindicated in IBS or any intestinal condition worsened by gas and distension
  • associated with reversible hepatic enzyme elevation
  • Periodical liver function monitoring is required with acarbose therapy

30

Incretin Analog: ____

DDP-4 inhibitor: ____

both ___ insulin secretion

GLP-1 analog: Exenatide

DDP-4 inhibitor: Sitagliptin (oral)

both increase insulin secretion