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Clin Therapeutics 2- Exam 3 > Diabetes Part 2 > Flashcards

Diabetes Part 2 Flashcards

1
Q

What is the target organ for sulfonylureas (SU)?

A

pancreas

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2
Q

What is the target organ for glinides?

A

pancreas

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3
Q

What are the target organs for biguanide (metformin)? (3)

A

liver, muscle, adipose tissue

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4
Q

What are the target organs for thiazolidinediones (TZD)? (3)

A

adipose tissue, muscle, liver

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5
Q

What is the target organ for alpha-glucosidase inhibitors (AGI)?

A

GIT (s. intestine)

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6
Q

What is the target organ for DPP-4 inhibitors?

A

GIT

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7
Q

What is the target organ for SGLT-2 inhibitors?

A

kidneys

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8
Q

What is the target organ for insulin?

A

liver

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9
Q

What are the target organs for GLP-1 receptor agonists? (4)

A

GIT, brain, liver, pancreas (beta cells)

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10
Q

What are the target organs for amylin analogue (pramlintide)? (3)

A

GIT, liver, brain

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11
Q

What is the MOA of sulfonylureas (SU)?

A

Enhance insulin secretion from beta cell (independent of glucose load)

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12
Q

What is the MOA of glinides?

A

Enhance insulin secretion from beta cell (independent of glucose load)

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13
Q

What is the MOA of biguanide (metformin)?

A

Decrease hepatic glucose production and increase insulin sensitivity

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14
Q

What is the MOA of TZDs?

A

Activate PPAR-gamma in muscle, liver, and fat leading to changes in gene transcription; inc glucose transporter expression

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15
Q

What is the MOA of AGIs?

A

Inhibit enzymes in the small intestine that hydrolyze polysaccharides into simple sugars→ delays absorption of dietary CHO

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16
Q

What is the MOA of DPP-4 inhibitors?

A

Inhibits enzyme responsible for the breakdown of endogenous GLP-1

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17
Q

What is the MOA of SGLT-2 inhibitors?

A

Inhibits the SGLT-2 transporter in the kidney to dec reabsorption of glucose→ inc urinary glucose excretion

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18
Q

What is the MOA of GLP-1 receptor agonists?

A

Enhances glucose dependent insulin secretion, slows gastric emptying, inc satiety, suppresses postprandial glucagon release, suppresses hepatic glucose production

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19
Q

What is the MOA of amylin analogue (pramlintide)?

A

Slows gastric emptying, inc satiety, suppresses postprandial glucagon release, suppresses hepatic glucose production

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20
Q

What are some clinical pearls of metformin? (7)

A

1) Cornerstone of T2DM tx- safe, effective, cheap, may reduce risk of CV and death
2) Low risk of hypoglycemia
3) Max therapeutic effect w/in 2 weeks
4) Effects FPG and PPG
5) Can cause Vit B12 deficiency in high doses w/long term use-monitor levels
6) Weight loss or neutral
7) Bad GI effects-diarrhea

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21
Q

What is the initial dose when starting on metformin?

A

500 mg daily

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22
Q

How is metformin titrated over 4 weeks, leading to the max clinical dose?

A

Week 1: 500 mg daily
Week 2: 500 mg BID
Week 3: 500 mg in AM, 1000 mg in PM
Week 4: 1000 mg BID→ max clinical dose

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23
Q

What formulation of metformin minimizes GI effects?

A

ER formulation

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24
Q

What are some clinical pearls of Sulfonylureas (SU)? (6)

A

1) Requires functioning beta-cells
2) Primarily affects FPG
3) Max therapeutic effects at 50% MDD
4) Avoid glyburide: long acting, high risk of hypoglycemia, long half life and active metabolite
5) HIGH risk of hypoglycemia
6) Limited durability: usually good for 6 months w/high secondary failure after

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25
Q

What are the 3 SU drugs?

A

1) Glyburide
2) Glipizide
3) Glimeperide

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26
Q

What are the 2 glinide drugs?

A

1) Repalinide

2) Nateglinide

27
Q

What are some clinical pearls of glinides? (4)

A

1) Requires functioning beta-cells
2) Effects PPG
3) Requires multiple doses daily (before meals)
4) Less risk of hypoglycemia vs. SUs b/c rapid onset and short duration of action

28
Q

What are the 2 TZD drugs?

A

1) pioglitazone

2) rosiglitazone

29
Q

What are some clinical pearls of TXDs? (5)

A

1) Insulin sensitizers
2) Primarily affects FPG
3) Max therapeutic effects seen at 8-12 weeks-titrating to max dose not recommended
4) Low hypoglycemia risk
5) Good A1c durability

30
Q

What are 5 SEs of pioglitazone?

A

1) edema
2) weight gain
3) atypical bone fractures
4) bladder cancer
5) macula edema

31
Q

What are 2 alpha-glucosidase inhibitors (AGIs)?

A

1) acarbose

2) miglitol

32
Q

What are some clinical pearls of AGIs? (5)

A

1) Affects PPG
2) Most effective if diet contains large amounts of carbs
3) Requires multiple daily doses-must be present in gut to work
4) Max therapeutic effects 1 hr after eating
5) Titrate over 4-8 weeks to minimize GI SEs (abd pain, flatulence, bloating)→ poor tolerability, not used often

33
Q

What are 4 DPP-4 inhibitors?

A

1) lingagliptin
2) alogliptin
3) sitagliptin
4) saxagliptin

34
Q

What are some clinical pearls of DPP-4 inhibitors? (7)

A

1) Primarily PPG
2) Modestly effective at lowering A1c
3) Max therapeutic effect in 2 weeks
4) Weight neutral
5) Well tolerated (SEs: HA, rash, nasopharyngitis)
6) Low hypoglycemia risk
7) May need to reduce dose of SU if given in combo

35
Q

What are 3 SGLT-2 inhibitors?

A

1) canagliflozin
2) empagliflozin
3) dapagliflozin

36
Q

What are 4 benefits of SGLT-2 inhibitors?

A

1) useful for all durations of diabetes: not dependent on beta cell for efficacy; primarily affects FPG
2) weight loss
3) low risk of hypoglycemia
4) CV data

37
Q

What are 3 safety concerns of SGLT-2 inhibitors?

A

1) inc incidence of UTIs and genital infections
2) dec BP
3) acute kidney injury

38
Q

What are 5 GLP-1 receptor agonists?

A

1) exenatide
2) liraglutide
3) albiglutide
4) dulaglutide
5) lixisenatide

39
Q

What are some clinical pearls of GLP-1 receptor agonists? (7)

A

1) Work on multiple pathophys targets
2) Inc insulin secretion from beta cells-glucose dependent
3) May preserve beta-cell function and mass
4) Effects FPG and PPG
5) Weight loss of 2-4 kg over 12 weeks
6) Low hypoglycemia risk
7) Most approved to be used w/basal insulin-no FDA approval for prandial insulin

40
Q

Which 3 GLP-1 agonists are daily?

A

1) exenatide (BID)
2) liraglutide
3) lixisenatide

41
Q

What 2 GLP-1 agonists are short acting?

A

1) exenatide (BID)

2) lixisenatide

42
Q

Which 3 GLP-1 agonists are weekly?

A

1) exenatide ER
2) dulaglutide
3) albiglutide

43
Q

Which 4 GLP-1 agonists are long acting?

A

1) exenatide ER
2) dulaglutide
3) albiglutide
4) liraglutide

44
Q

Which 2 GLP-1 agonists primarily cover PPG?

A

1) Exenatide (BID)

2) lixisenatide

45
Q

Which 4 GLP-1 agonists primarily cover FPG?

A

1) exenatide ER
2) dulaglutide
3) albiglutide
4) liraglutide

46
Q

What is the name of the amylin analogue?

A

pramlintide

47
Q

What are some clinical pearls of amylin analogue? (6)

A

1) Effects PPG
2) Slows gastric emptying, inc hunger, thirst
3) Must be used w/intensive insulin regimens (basal-bolus) → given w/mealtime insulin-must reduce dose of bolus insulin by 50% to avoid hypoglycemia
4) Works to complement the action of insulin
5) Requires multiple daily doses
6) SEs: N/V, anorexia, inc risk of insulin-induced hypoglycemia

48
Q

What are 5 drugs that affect FPG?

A

1) Metformin
2) SUs
3) TZDs
4) SGLT-2 inhibitors
5) GLP-1 receptor agonists

49
Q

What are 6 drugs that affect PPG?

A

1) Metformin
2) Glinides
3) AGIs
4) DPP-4 inhibitors
5) GLP-1 receptor agonists
6) Amylin analog

50
Q

What are 2 combinations to avoid when using combination therapy?

A

1) SU + glinides→ same MOA w/inc risk of hypoglycemia + beta-cell burnout
2) GLP-1 + DPP-4 inhibitor→ GLP-1 agonist does what DPP-4 inhibitors do + more and is more efficacious

51
Q

What 3 drugs are safe to use in pts with CV disease?

A

1) liraglutide
2) empagliflozin
3) metformin (obese pts)

52
Q

What 4 drugs/drug classes should be avoided in CV disease pts?

A

1) saxagliptin
2) alogliptin
3) TZDs
4) SUs

53
Q

Which 5 drugs/drug classes need to be avoided or dose reduced in renal disease?

A

1) metformin
2) SUs
3) DPP-4 inhibitors (except linagliptin)
4) exenatide (ER)
5) SGLT-2 inhibitors

54
Q

At what eGFR level is metformin C/I?

A

CrCl <30

55
Q

At what eGFR level is metformin not supposed to be initiated?

A

CrCl >/=30-45

56
Q

If eGFR 45-59, what do you do with the Canagliflozin dose? If <45?

A

Give 100 mg daily; if <45→ avoid

57
Q

At what eGFR level empagliflozin to be avoided?

A

<45

58
Q

At what eGFR level dapagliflozin to be avoided?

A

<60

59
Q

What are 4 drug classes that are at highest risk of hypoglycemia when used as monotherapy and what is the strategy to lessen the risk for each?

A
  • Insulin: strategy→ use rapid, long acting, and ultra-long acting
  • SUs: strategy→ take w/food
  • Glinides: strategy→ take w/food
  • Amylin analog: strategy→ reduce dose of bolus insulin by 50%
60
Q

Which 3 medication classes cause weight loss?

A

1) GLP-1 agonists
2) amylin analogue
3) SGLT-2 inhibitors

61
Q

Which 3 medication classes are weight neutral?

A

1) metformin
2) DPP-4 inhib
3) AGIs

62
Q

Which 4 medication classes cause weight gain?

A

1) TZDs
2) SUs
3) glinides
4) insulin

63
Q

Which 8 medication classes are taken orally?

A
  • Metformin
  • SUs
  • Glinides
  • TZDs
  • AGIs
  • DPP-4 inhibitors
  • SGLT-2 inhibitors
  • Afrezza (inhaled)
64
Q

Which 3 medication classes are SC injectables?

A
  • GLP-1 agonists
  • Amylin analogues
  • Insulin (basal, bolus)

Clin Therapeutics 2- Exam 3 (3 decks)

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