04 Thera VI T2DM Oral Therapies Diane Flashcards Preview

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Flashcards in 04 Thera VI T2DM Oral Therapies Diane Deck (103):
1

What is the pathophysiology of the pancreas in T2DM?

Impaired insulin secretion. Progressive loss of beta cell function

2

What is the pathophysiology of the liver in T2DM?

Impaired insulin sensitivity. Increased gluconeogenesis (glucose production)

3

What is the pathophysiology of the muscle and adipose tissue in T2DM?

Insulin resistance. Decreased glucose uptake

4

What is the pathophysiology of the GI tract in T2DM?

Site of glucose absorption. Decreased prandial response to glucose and incretin effect

5

What are the ADA adult glycemic goals?

A1c < 7%. FPG 70-130. 2hr PP < 180

6

What are the AACE adult glycemic goals?

A1c < 6.5%. FPG < 110. 2hr PP < 140

7

What drugs are Biguanides?

Metformin

8

What is the MOA of Metformin?

Activates AMP-kinase: Decreases hepatic glucose production, decreases GI glucose absorption, improves peripheral glucose sensitivity

9

What is the A1c efficacy of Metformin?

Decreases it by 1-2%

10

What is the positive side of using Metformin?

NO weight gain or hypoglycemia associated. Can also improve the lipid panel (Decrease TG and LDL)

11

What is the Onset time of Metformin?

Days, max effect up to 2 weeks

12

How is Metformin metabolized/excreted?

No hepatic metabolism. 100% renally excreted

13

How is Metformin dosed?

Initial: 500mg BID or 850mg daily. Max: 2550mg/day (no added benefit > 2g/day)

14

How is Metformin ER dosed?

Initial: 500mg/day. Max 2000mg/day

15

What needs to be remembered about the administration of Metformin?

TAKE WITH FOOD. Titrate slowly

16

What are the common ADRs associated with Metformin?

GI effects: N/V/D, flatulence, abdominal discomfort (these are less with ER)

17

What are the counseling points with Metformin?

Recommend patients to take with food to decrease GI side effects. The side effects are transient, will improve over time

18

What is a rare side effect of Metformin (BBW)?

Lactic Acidosis. Risk increases with renal impairment and hypoxemia. Labs will show an increase in lactate (>5mmol), decreased blood pH, and electrolyte abnormalities (increase in anion gap)

19

What are the symptoms of Lactic Acidosis?

Very non-specific (need labs to prove it). N/V/D, hyperventilation, malaise, lethargy, myalgias

20

What are the contraindications associated with Metformin?

Hypersensitivity. Renal dysfunction (Scr > 1.5 for men and > 1.4 for women). Acute or chronic metabolic acidosis. Radiological studies with iodinated contrast (hold 48 hours prior to and after procedure)

21

What should you use caution with Metformin?

Chronic hepatic dysfunction (reduced lactate clearance). Hypoxic states (excessive alcohol, CHF, surgery)

22

What are the indications for Sulfonylureas?

Considered second-line to be added on to metformin and combination with insulin or other oral agents (except meglitinides). Can be used first-line in patients who cannot tolerate metformin

23

What are the main Sulfonylureas used?

Glimeperide (Amaryl). Glipizide (Glucotrol). Glyburide (DiaBeta, Micronase, Glynase)

24

What is the MOA of Sulfonylureas?

Binds ATP-dependent K channels --> depolarization of B-cells --> Ca influx --> increase insulin release. Partially reverses insulin secretory defect associated with T2DM

25

What is a drawback to Sulfonylurea use?

Effectiveness will decline over time

26

How much do Sulfonylureas decrease A1c?

1-2%. All agents equally effective

27

How are Sulfonylureas metabolized and eliminated?

Metabolism: Hepatic. Elimination: Renal (urine), feces

28

Which Sulfonylurea has the fastest onset?

Glyburide (1h). Glipizide (1-3h). Glimepiride (2-3h)

29

Which Sulfonylurea has the shortest duration of action?

Glipizide (10-14h). Glyburide (12-24). Glimepiride (24h)

30

Which Sulfonylureas have active metabolites?

Only Glimepiride and Glyburide

31

What are the CrCl levels that you need to use caution with the Sulfonylureas?

Glipizide (< 10). Glimepiride (< 22). Glyburide (< 50)

32

Which Sulfonylureas need to be taken with food?

"-ride": Glimepiride and Glyburide

33

When does Glipizide need to be taken?

Take 30 minutes before meals

34

Which Sulfonylureas have BID dosing?

Glyburide and Glipizide

35

Which Sulfonylureas have QD dosing?

Glimepiride and Glipizide ER

36

What are the common ADRs associated with Sulfonylureas?

Hypoglycemia. Weight gain (2-5kg)

37

What are the rare ADRs associated with Sulfonylureas?

GI (N, dypepsia). Photosensitivity. Skin rash

38

Which Sulfonylurea is usually ok to use with Sulfa allergies?

Glimepiride

39

What are contraindications for Sulfonylurea use?

Hypersensitivity. T1DM (they don't have working B-cells to release insulin). Diabetic Ketoacidosis

40

When should you use caution when using a Sulfonylurea agent?

Sulfa allergy. Renal dysfunction

41

When are Meglitinides recommended?

May be used first line in patients who cannot take metformin or in place of SFU in patients with irregular eating schedules

42

What are the Meglitinide drugs?

Repaglinide (Prandin) and Nateglinide (Starlix)

43

What is the MOA of Meglitinides?

Similar to SFU (increase insulin production). Fast onset and shorter duration. Target post-prandial glucose

44

How much is A1c lowered by Meglitinides?

1-1.5%

45

How are Meglitinides metabolized and eliminated?

Metabolism: Hepatic. Elimination: Renal (urine), feces

46

What is the onset time for Meglitinides?

Nateglinide (20 hours). Repaglinide (15-60 hours)

47

When are Meglitinides taken?

Taken with meals. Skip dose if skipping meal. Start with lowest possible dose (caution in elderly)

48

What are the common ADRs associated with Meglitinides?

Hypoglycemia (Repaglinide > Nateglinide). Weight gain. HA. Upper respiratory infection

49

When are Meglitinides contraindicated?

Hypersensitivity. T1DM. DKA. Repaglinide: concurrent gemfibrozil therapy

50

When should you use caution before Meglitinide use?

Caution in renal/hepatic impairment

51

When are Thiazolidinediones indicated?

Approved for monotherapy and combination therapy with metformin, DPP-4 inhibitors, incretin mimetics, SFU

52

What are the Thiazolidinediones drugs?

Prioglitazone (Actos). Rosiglitazone (Avandia)

53

What is the MOA of Thiazolidinediones?

Activate PPARy nuclear receptors (muscle and fat tissue). Decrease peripheral insulin resistance (insulin sensitizer). Decrease hepatic glucose output

54

How much is A1c lowered by Thiazolidinediones?

1-1.5%

55

How do Thiazolidinediones affect the lipid profile?

Pioglitazone: decrease TG and increase HDL. Rosiglitazone: Increase LDL

56

What is the onset time for Thiazolidinediones?

Delayed. Up to 3 months for maximum effect. Works on gene translation, protein production

57

How are Thiazolidinediones metabolized and eliminated?

Metabolism: Hepatic. Elimination: Urine and feces

58

What is the BBW associated with Thiazolidinediones?

CHF (may cause or worsen CHF, not recommended for patients with symptomatic HF (class III and IV). Monitor patients for s/sx of HF after initiation and when increasing dose

59

What is cardiovascular safety like for Thiazolidinediones?

43% higher incidence of MI with Rosiglitazone use. Pioglitazone have some CV protection

60

What is the use of Rosiglitazone limited to?

Patients already being successfully treated with it. Patients who cannot be controlled with other anti-diabetic medicines. Consulted with MD and do not wish to use pioglitazone containing medicines

61

What is a major risk of Pioglitazone use?

Risk of bladder cancer increased with increasing dose (reaching statistical significance after 24 months). Do not use Pioglitazone for longer than 1 year. Counsel patients to report s/sx of blood in urine, urinary urgency, pain on urination, or back or abdominal pain

62

What is the administration of Thiazolidinediones like?

Once daily dosing. Can take without regard to meals. Brand only. No renal dose adjustment

63

What are the common ADRs associated with Thiazolidinediones?

Weight gain. Edema. Increased subcutaneous adipose

64

What are the rare ADRs associated with Thiazolidinediones?

Hepatic failure. Decreased WBC, Hgb, and platelets

65

What are the contraindications to Thiazolidinediones use?

NYHA Functional Class III/IV HF. ALT > 2.5x upper normal limit

66

When should you use caution before Thiazolidinediones use?

Cardiac disease. Edema. Hepatic disease. Bladder cancer (Pioglitazone)

67

When are alpha-Glucosidase Inhibitors indicated?

Approved for monotherapy or combination with metformin

68

What are the alpha-Glucosidase Inhibitors drugs?

Acarbose (Precose). Miglitol (Glyset)

69

What is the MOA of alpha-Glucosidase Inhibitors?

Decrease absorption of carbohydrates in small intestines. Inhibit small intestine brush border enzymes. Targets post-prandial glucose

70

How much is the A1c lowered with alpha-Glucosidase Inhibitors?

0.5-1%

71

What is the absorption like for alpha-Glucosidase Inhibitors?

Acarbose is poor (1-2%). Miglitol has saturable absorption (25mg completely absorbed, 100mg ~50-70% absorption)

72

How are alpha-Glucosidase Inhibitors metabolized and eliminated?

Metabolism: Acarbose metabolized by intestinal bacteria and digestive enzymes in GI, Miglitol is not metabolized. Excretion: Renal (miglitol), fecal (acarbose)

73

What is the administration of alpha-Glucosidase Inhibitorslike?

Taken with meals. Skip dose if skipping meal. Slow titration - based on one hour post-prandial and to decrease GI upset

74

What are the common ADRs assocaited with alpha-Glucosidase Inhibitors?

GI side effects (gas, bloating, diarrhea)

75

What are the rare ADRs associated with alpha-Glucosidase Inhibitors?

Increased LFTs. Hepatic failure

76

What are the contraindications for alpha-Glucosidase Inhibitors?

Chronic GI disease (IBD, Crohns, obstruction)

77

When should you use caution before using alpha-Glucosidase Inhibitors?

Renal/hepatic impairment

78

What are the indications for Dipeptidyl Peptidase-4 (DPP-4) Inhibitors?

Approved for monotherapy and in combination with metformin, TZDs, SFUs

79

What are the DPP-4 Inhibitors drugs?

Sitagliptin (Januvia). Saxagliptin (Onglyza). Linagliptin (Tradjenta)

80

What is the MOA of DPP-4 Inhibitors?

Inhibit DPP-4 --> increase endogenous incretins (GLP-1 and GIP). Early satiety. Increase insulin release in response to ingested glucose. Decrease pancreatic secretion of glucagon. Slowed gastric emptying

81

How much is A1c lowered with DPP-4 Inhibitors?

0.5-1%

82

Which DPP-4 Inhibitors are excreted renally?

Sitagliptin. Saxagliptin

83

Which DPP-4 Inhibitor is excreted 80% bile (enterohepatic), minimal renal?

Linagliptin

84

How is Sitagliptin renally adjusted?

CrCl 30-50: 50mg daily. CrCl < 30: 25mg daily

85

How is Saxagliptin renally adjusted?

CrCl < 50: 2.5mg daily

86

How is Linagliptin renally adjusted?

No renal adjustment needed

87

What are the ADRs associated with Sitagliptin?

GI side effects. URI. Nasopharyngitis

88

What are the ADRs associated with Saxagliptin?

Peripheral edema. Hypoglycemia

89

What are the ADRs associated with Linagliptin?

Nasopharyngitis. Hypoglycemia

90

What is the combination product: Metformin + Glyburide?

Glucovance

91

What is the combination product: Metformin + Glipizide?

Metaglip

92

What is the combination product: Metformin + Pioglitazone?

Actoplus Met

93

What is the combination product: Metformin + Rosiglitazone?

Avandamet

94

What is the combination product: Metformin + Sitagliptin?

Janumet

95

What is the combination product: Metformin + Linagliptin?

Jentadueto

96

What is the combination product: Glimeperide + Pioglitazone?

Duetact

97

What is the combination product: Glimperide + Rosiglitazone?

Avandaryl

98

What are your best drug choices to avoid weight gain?

Metformin. DPP-4 Inhibitors

99

What are the best drug choices to avoid GI symptoms?

SFUs. Meglitinides. TZDs. DPP-4 Inhibitors

100

What are the best drug choices to avoid Hypoglycemia?

Metformin. TZDs. DPP-4 Inhibitors

101

What are the best drug choices with impaired renal function?

Meglitinides. TZDs

102

What are the best drug choices with impaired hepatic function?

SFUs. DPP-4 Inhibitors

103

What are the best drug choices with impaired CV/pulmonary function?

SFUs. Meglitinides. DPP-4 Inhibitors