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Endorine > T2D Meds > Flashcards

T2D Meds Flashcards

1
Q

Which drugs are not contraindicated in preg?

A

Only sulfonylurea (glyburide) and metformin

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2
Q

What should sulfonylureas not be used with?

A

Meglitinides, otherwise all drugs can be used in combination

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3
Q

What is the first drug of choice?

A

Metformin

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4
Q

What is the action of Metformin/Biguanides

A

Reduces hepatic gluconeogenesis and possibly glycogenolysis

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5
Q

What is the mechanism of Metformin/Biguanides

A

Activation/phos of AMPK (amp actiavted protein kinase)

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6
Q

What is the effect of Metformin/Biguanides

A

Improves pre-meal glucose with some effect on post-prandial glucose. It is weight neutral and can induce weight loss (inc satiety)

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7
Q

What is the metabolism of Metformin/Biguanides

A

Not metabolized. Renally excreted unchanged so can accumulate if pt has a renal insufficiency and cause the same toxicity as fen fen weight loss drug (lactic acidosis)

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8
Q

Describe Metformin/Biguanides onset

A

immediate

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9
Q

What do we do to avoid side effects of Metformin/Biguanides

A

Increase the dose slowly at 1 week intervals to avoid gastrointestinal side effects. Does not cause hypoglycemia

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10
Q

Contraindications of Metformin/Biguanides

A

Prone to metabolic acidosis, hypoxic states, renal failure, cardiac ischemia, T1D

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11
Q

What does Metformin/Biguanides require for its action?

A

Presence of insulin

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12
Q

What is the efficacy of Metformin/Biguanides?

A

Lowers A1c as much as 2%

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13
Q

What is the specific MOA of Metformin/Biguanides?

A

Activates AMPK via phosphorylation→ ↓ACC activity and ↓ hepatic glucose production (gluconeogenesis and possibly glycogenolysis), sensitizes insulin

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14
Q

What are some advantages to T2D oral drugs? Ie what do we look for when we prescribe them?

A
  • Weight neutral or weight loss
  • No hypoglycemia
  • Less frequent administration = better compliance
  • Oral administration
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15
Q

What are some disadvantages to T2D oral drugs? Ie what do we look for that they dont do when we prescribe them?

A
  • Weight gain- this is caused by the reversal of osmotic diuresis, the normalization of glucose (since they have been undergoing starvation due to inability to utilize glucose), and fluid retention (specifically with thiazolidinediones)
  • Possibility of hypoglycemia- this is associated with drugs that stimulate insulin secretion
  • More frequent administration
  • Injection administration (pts don’t like this)
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16
Q

What are 2 insulin secretagogues?

A

Sulfonylureas and Meglitinides/Glinides

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17
Q

What is the action of Sulfonylureas?

A

Stimulates pancreatic insulin secretion for 12-24 hours

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18
Q

What is the mechanism of Sulfonylureas?

A

Binds to sulfonyl receptor in beta cell resulting in depolarization of ATP dependent potassium channels

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19
Q

What is the effect of Sulfonylureas?

A

It is immediate, mostly on pre-meal/fasting glucose

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20
Q

What is the metabolism of Sulfonylureas?

A

Hepatic, excreted via kidney with active metabolites so caution in renal impairment

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21
Q

What are the contraindications of Sulfonylureas?

A

T1D, DKA, sulfa allergy

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22
Q

What are the adverse events of Sulfonylureas?

A

Hypoglycemia, weight gain, hunger

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23
Q

What is the efficacy of Sulfonylureas?

A

Lowers A1c up to 1.5%

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24
Q

What is the specific mechanism of actions of Sulfonylureas?

A

Binds to sulfonyl receptor in b cell→ depolarization of ATP-dependent K+ channels→ causes increase influx of Ca2+→ stims insulin secretion for 12-24 hrs

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25
Q

What is the action of Meglitinides/Glinides

A

Stimulates pancreatic insulin secretion for 3-4 hours, same binding site as sulfonylureas

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26
Q

What is the mechanism of Meglitinides/Glinides?

A

Stimulates insulin release by regulating ATP sensitive K+ channels on beta cells

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27
Q

What is the speed of onset of Meglitinides/Glinides?

A

Fast

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28
Q

What are the side effects of Meglitinides/Glinides?

A

Low glucose 2-4 hours after meal, wt gain, patient compliance (have to take 3x/d)

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29
Q

What are the contraindications of Meglitinides/Glinides?

A

T1DM, Liver failure, DKA, sulfa allergy

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30
Q

What is the metab of Meglitinides/Glinides?

A

Hepatic by cytochrome P450 enzyme system, 96% metabolites excreted via GI tract

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31
Q

What is the efficacy of Meglitinides/Glinides?

A

Lowers A1c by about 0.4% (not very efficacious)

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32
Q

What is the action of Thiazolidinediones?

A

Decreases peripheral insulin resistance in skeletal muscle, adipose tissue, liver

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33
Q

What is the mechanism of Thiazolidinediones?

A

-Binds to nuclear PPARgamma receptor causing inc transcription of GLUT4 transporter

34
Q

How is Thiazolidinediones administered?

A

Pill by mouth 1-2x day

35
Q

What is the effect of Thiazolidinediones?

A

Lowers pre-meal and post-meal glucose

36
Q

Side effects of Thiazolidinediones?

A

Weight gain (improved glycemic control and IV volume expansion related to Na reabsorption

Hepatocellular injury

PPARgamma is also in renal tubules, causes Na reabsorption increasing total vol of water leading to dilution anemia and heart has to work harder

37
Q

What are the contraindications of Thiazolidinediones?

A

Acute liver dis, heart failure, renal insufficiency

38
Q

What do Thiazolidinediones do to cholesterol?

A

Reduces plasma TGs but inc LDL-cholesterol, raises HDL

39
Q

How quickly do Thiazolidinediones work?

A

Slow onset of action, fasting glucose begins to dec within 5-7 days, but does not achieve a steady state for 2-3 mo

40
Q

What do Thiazolidinediones do to glucose?

A

Does not induce low blood glucose. Sensitizes insulin, but does not increase insulins secretion

41
Q

How efficacious is Thiazolidinediones?

A

Lowers A1c up to 1.8%

42
Q

What is the action of alpha-Glucosidase Inhibitors?

A

Delays gut carb absorption, inc GLP-1

43
Q

What is the mechanism of alpha-Glucosidase Inhibitors?

A

Competitively inhibits the ability of enzymes in the small intestinal brush border to break down oligosaccharides and disaccharides into monosaccharides

44
Q

What are the affects of alpha-Glucosidase Inhibitors?

A

Post prandial glucose ONLY

45
Q

How are alpha-Glucosidase Inhibitors administered?

A

Pill taken with meals

46
Q

What are the side effects of alpha-Glucosidase Inhibitors?

A

Flatulence, abdominal bloating

47
Q

What are the contraindications for alpha-Glucosidase Inhibitors?

A

GI disorders esp. inflammatory bowel dis

48
Q

How do we dose alpha-Glucosidase Inhibitors?

A

titrate slowly to min GI side effects

49
Q

What is the metabolism of alpha-Glucosidase Inhibitors?

A

Renally excreted as unchanged drug

50
Q

What is alpha-Glucosidase Inhibitors effect on glucose?

A

Does not induce low glucose

51
Q

What is the efficacy of alpha-Glucosidase Inhibitors?

A

Lowers A1c about 0.4%

52
Q

What enzyme breaks down incretin hormones?

A

DPP-4: ubiquitous, serine protease that cleaves the N terminal dipeptide

53
Q

How fast does GLP-1 inactivate?

A

> 50% in 1 min before it reaches general circulation. >40% is already degraded before it reaches beta cells

54
Q

How fast does GIP inactivate?

A

> 50% in 7 min

55
Q

What is the incretin effect?

A

Incretin is responsible for the first response of insulin about 1 hour after a meal (?)

56
Q

What is a GLP-1 analog/receptor agonist?

A

Exenatide, made from Gila monster’s saliva (long acting GLP-1 agonist)

Liraglutide

57
Q

How does exenatide work?

A

Augments insulin and is glucose dependent, suppresses glucagon secretion, slows gastric motility, induces satiety, reduces weight, may preserve/restore beta cell fxn/mass, greater potency and duration than native GLP1

58
Q

Is Exenatide long or short acting?

A

Long-acting

59
Q

How is Exenatide given?

60
Q

What is Exenatide’s effect on glucose?

A

Predominantly reduces post prandial glucose

61
Q

What is the action of Exenatide?

A

Potent glucose-dep insulin secretion inhibits glucagon secretion, slows gastric emptying, stimulates satiety

62
Q

What is the metabolism of Exenatide?

A

Renally excreted after enz degraded by DPP-4

63
Q

What is the side effect of Exenatide?

64
Q

What is the contraindication of Exenatide?

A

Gastroparesis

65
Q

What is Exenatide’s effect on hypoglycemia?

A

Can’t induce hypoglycemia because it is glucose dep

66
Q

What is the efficacy of Exenatide?

A

Lowers A1c as much as 1%

67
Q

What is a positive extra benefit of Exenatide?

A

It causes a weight loss of 5.3kg

68
Q

Besides giving exogenous GLP-1, what is another way to inc GLP-1 potency?

A

Inhibit DDP-4, increasing duration of action of GLP-1

69
Q

What is the action of Incretin Enhancers/DPP-4 Inhibitors?

A

Increases duration of action of GLP-1

70
Q

What is the mechanism of Incretin Enhancers/DPP-4 Inhibitors?

A

Inhibits DPP-4 with 80% inhibition at 24 hrs

71
Q

How quickly do Incretin Enhancers/DPP-4 Inhibitors work?

A

Immediately, mostly on post-meal glucose

72
Q

What is the metab of Incretin Enhancers/DPP-4 Inhibitors?

A

Not metab, excreted unchanged through kidneys, dose adj for renal insufficiency

73
Q

How is Incretin Enhancers/DPP-4 Inhibitors administered?

A

Orally daily

74
Q

What are the contraindications of Incretin Enhancers/DPP-4 Inhibitors?

75
Q

What are Incretin Enhancers/DPP-4 Inhibitors effects on hypoglycemia and weight

A

Does not induce hypogly and weight neutral

76
Q

What is the efficacy of Incretin Enhancers/DPP-4 Inhibitors?

A

Lowers A1c by about 0.7%

77
Q

What is the MOA of Conagliflozin, Dapagliflozin?

A

Inhibits SGLT2 (Na+/gluc cotransporter in the kidney that facilitates reabsorption of glucose into blood) increasing excretion of excess glucose into urine

78
Q

What is the metab of Conagliflozin, Dapagliflozin?

A

Mainly hepatic with some metab excreted via kidney

79
Q

What are the contraindications of Conagliflozin, Dapagliflozin?

A

Severe renal impairment, ESRD, or on dialysis

80
Q

What are the side effects of Conagliflozin, Dapagliflozin?

A

Vulvovaginal candidiasis, vulvovaginal mycotic infection, UTI, polyuria

81
Q

What is the efficacy of Conagliflozin, Dapagliflozin?

A

Lowers A1c by 0.7%

82
Q

What is the weight effects of Conagliflozin, Dapagliflozin?

A

Weight loss of about 2.2%

Endorine (24 decks)

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