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Thera VI > 04 Thera VI T2DM Oral Therapies Diane > Flashcards

04 Thera VI T2DM Oral Therapies Diane Flashcards

1
Q

What is the pathophysiology of the pancreas in T2DM?

A

Impaired insulin secretion. Progressive loss of beta cell function

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2
Q

What is the pathophysiology of the liver in T2DM?

A

Impaired insulin sensitivity. Increased gluconeogenesis (glucose production)

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3
Q

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

A

Insulin resistance. Decreased glucose uptake

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4
Q

What is the pathophysiology of the GI tract in T2DM?

A

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

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5
Q

What are the ADA adult glycemic goals?

A

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

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6
Q

What are the AACE adult glycemic goals?

A

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

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7
Q

What drugs are Biguanides?

A

Metformin

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8
Q

What is the MOA of Metformin?

A

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

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9
Q

What is the A1c efficacy of Metformin?

A

Decreases it by 1-2%

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10
Q

What is the positive side of using Metformin?

A

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

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11
Q

What is the Onset time of Metformin?

A

Days, max effect up to 2 weeks

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12
Q

How is Metformin metabolized/excreted?

A

No hepatic metabolism. 100% renally excreted

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13
Q

How is Metformin dosed?

A

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

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14
Q

How is Metformin ER dosed?

A

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

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15
Q

What needs to be remembered about the administration of Metformin?

A

TAKE WITH FOOD. Titrate slowly

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16
Q

What are the common ADRs associated with Metformin?

A

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

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17
Q

What are the counseling points with Metformin?

A

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

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18
Q

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

A

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)

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19
Q

What are the symptoms of Lactic Acidosis?

A

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

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20
Q

What are the contraindications associated with Metformin?

A

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)

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21
Q

What should you use caution with Metformin?

A

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

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22
Q

What are the indications for Sulfonylureas?

A

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

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23
Q

What are the main Sulfonylureas used?

A

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

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24
Q

What is the MOA of Sulfonylureas?

A

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

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25
Q

What is a drawback to Sulfonylurea use?

A

Effectiveness will decline over time

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26
Q

How much do Sulfonylureas decrease A1c?

A

1-2%. All agents equally effective

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27
Q

How are Sulfonylureas metabolized and eliminated?

A

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

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28
Q

Which Sulfonylurea has the fastest onset?

A

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

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29
Q

Which Sulfonylurea has the shortest duration of action?

A

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

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30
Q

Which Sulfonylureas have active metabolites?

A

Only Glimepiride and Glyburide

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31
Q

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

A

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

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32
Q

Which Sulfonylureas need to be taken with food?

A

“-ride”: Glimepiride and Glyburide

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33
Q

When does Glipizide need to be taken?

A

Take 30 minutes before meals

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34
Q

Which Sulfonylureas have BID dosing?

A

Glyburide and Glipizide

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35
Q

Which Sulfonylureas have QD dosing?

A

Glimepiride and Glipizide ER

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36
Q

What are the common ADRs associated with Sulfonylureas?

A

Hypoglycemia. Weight gain (2-5kg)

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37
Q

What are the rare ADRs associated with Sulfonylureas?

A

GI (N, dypepsia). Photosensitivity. Skin rash

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38
Q

Which Sulfonylurea is usually ok to use with Sulfa allergies?

A

Glimepiride

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39
Q

What are contraindications for Sulfonylurea use?

A

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

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40
Q

When should you use caution when using a Sulfonylurea agent?

A

Sulfa allergy. Renal dysfunction

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41
Q

When are Meglitinides recommended?

A

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

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42
Q

What are the Meglitinide drugs?

A

Repaglinide (Prandin) and Nateglinide (Starlix)

43
Q

What is the MOA of Meglitinides?

A

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

44
Q

How much is A1c lowered by Meglitinides?

A

1-1.5%

45
Q

How are Meglitinides metabolized and eliminated?

A

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

46
Q

What is the onset time for Meglitinides?

A

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

47
Q

When are Meglitinides taken?

A

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

48
Q

What are the common ADRs associated with Meglitinides?

A

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

49
Q

When are Meglitinides contraindicated?

A

Hypersensitivity. T1DM. DKA. Repaglinide: concurrent gemfibrozil therapy

50
Q

When should you use caution before Meglitinide use?

A

Caution in renal/hepatic impairment

51
Q

When are Thiazolidinediones indicated?

A

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

52
Q

What are the Thiazolidinediones drugs?

A

Prioglitazone (Actos). Rosiglitazone (Avandia)

53
Q

What is the MOA of Thiazolidinediones?

A

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

54
Q

How much is A1c lowered by Thiazolidinediones?

A

1-1.5%

55
Q

How do Thiazolidinediones affect the lipid profile?

A

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

56
Q

What is the onset time for Thiazolidinediones?

A

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

57
Q

How are Thiazolidinediones metabolized and eliminated?

A

Metabolism: Hepatic. Elimination: Urine and feces

58
Q

What is the BBW associated with Thiazolidinediones?

A

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
Q

What is cardiovascular safety like for Thiazolidinediones?

A

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

60
Q

What is the use of Rosiglitazone limited to?

A

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
Q

What is a major risk of Pioglitazone use?

A

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
Q

What is the administration of Thiazolidinediones like?

A

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

63
Q

What are the common ADRs associated with Thiazolidinediones?

A

Weight gain. Edema. Increased subcutaneous adipose

64
Q

What are the rare ADRs associated with Thiazolidinediones?

A

Hepatic failure. Decreased WBC, Hgb, and platelets

65
Q

What are the contraindications to Thiazolidinediones use?

A

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

66
Q

When should you use caution before Thiazolidinediones use?

A

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

67
Q

When are alpha-Glucosidase Inhibitors indicated?

A

Approved for monotherapy or combination with metformin

68
Q

What are the alpha-Glucosidase Inhibitors drugs?

A

Acarbose (Precose). Miglitol (Glyset)

69
Q

What is the MOA of alpha-Glucosidase Inhibitors?

A

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

70
Q

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

A

0.5-1%

71
Q

What is the absorption like for alpha-Glucosidase Inhibitors?

A

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

72
Q

How are alpha-Glucosidase Inhibitors metabolized and eliminated?

A

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

73
Q

What is the administration of alpha-Glucosidase Inhibitorslike?

A

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

74
Q

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

A

GI side effects (gas, bloating, diarrhea)

75
Q

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

A

Increased LFTs. Hepatic failure

76
Q

What are the contraindications for alpha-Glucosidase Inhibitors?

A

Chronic GI disease (IBD, Crohns, obstruction)

77
Q

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

A

Renal/hepatic impairment

78
Q

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

A

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

79
Q

What are the DPP-4 Inhibitors drugs?

A

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

80
Q

What is the MOA of DPP-4 Inhibitors?

A

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
Q

How much is A1c lowered with DPP-4 Inhibitors?

A

0.5-1%

82
Q

Which DPP-4 Inhibitors are excreted renally?

A

Sitagliptin. Saxagliptin

83
Q

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

A

Linagliptin

84
Q

How is Sitagliptin renally adjusted?

A

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

85
Q

How is Saxagliptin renally adjusted?

A

CrCl < 50: 2.5mg daily

86
Q

How is Linagliptin renally adjusted?

A

No renal adjustment needed

87
Q

What are the ADRs associated with Sitagliptin?

A

GI side effects. URI. Nasopharyngitis

88
Q

What are the ADRs associated with Saxagliptin?

A

Peripheral edema. Hypoglycemia

89
Q

What are the ADRs associated with Linagliptin?

A

Nasopharyngitis. Hypoglycemia

90
Q

What is the combination product: Metformin + Glyburide?

A

Glucovance

91
Q

What is the combination product: Metformin + Glipizide?

A

Metaglip

92
Q

What is the combination product: Metformin + Pioglitazone?

A

Actoplus Met

93
Q

What is the combination product: Metformin + Rosiglitazone?

A

Avandamet

94
Q

What is the combination product: Metformin + Sitagliptin?

A

Janumet

95
Q

What is the combination product: Metformin + Linagliptin?

A

Jentadueto

96
Q

What is the combination product: Glimeperide + Pioglitazone?

A

Duetact

97
Q

What is the combination product: Glimperide + Rosiglitazone?

A

Avandaryl

98
Q

What are your best drug choices to avoid weight gain?

A

Metformin. DPP-4 Inhibitors

99
Q

What are the best drug choices to avoid GI symptoms?

A

SFUs. Meglitinides. TZDs. DPP-4 Inhibitors

100
Q

What are the best drug choices to avoid Hypoglycemia?

A

Metformin. TZDs. DPP-4 Inhibitors

101
Q

What are the best drug choices with impaired renal function?

A

Meglitinides. TZDs

102
Q

What are the best drug choices with impaired hepatic function?

A

SFUs. DPP-4 Inhibitors

103
Q

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

A

SFUs. Meglitinides. DPP-4 Inhibitors

Thera VI (27 decks)

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