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PT 2 > Block 9 - L5-L6 > Flashcards

Block 9 - L5-L6 Flashcards

1
Q

What is diabetes mellitus?

A

Metabolic disorder characterized by hyperglycemia caused by a defect in either - insulin production, insulin responsiveness, or a combination of the two.

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2
Q

Normally, what does insulin do?

A

Increases glucose uptake into cells

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3
Q

What happens in Type I DM?

A

Insulin-producing beta cells are destroyed via autoimmune causes, leading to insulin deficiency. Glucose cannot be taken up into the cells because there is no insulin to bind to the cells and trigger this process.

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4
Q

What is the general form of treatment used for DM1?

A

Insulin replacement therapy

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5
Q

What happens in Type 2 DM?

A

Insulin resistance leads to a decreased insulin response and an inability to take up glucose

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6
Q

What is the general form of treatment used for DM2?

A

Insulin sensitizers, insulin secretagogues, insulin/other drugs

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7
Q

How is high glucose regulated normally?

A

High glucose activates the release of insulin from beta cells of the pancreas. Insulin causes increased glucose uptake in the liver; increased glucose uptake, TG synthesis, decreased lipolysis, and decreased FFA/glycerol in adipose tissue; increased glucose uptake, amino amino acid synthesis, and glycogen synthesis in muscle; all leads to decreased glucose

In addition, the alpha-cells are inhibited from releasing glucagon, which normally causes increased gluconeogenesis and glycogenolysis in the liver.

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8
Q

What are the symptoms of DM 1?

A

Polyuria, polydipsia, glucosuria, unexplained weight loss despite polyphagia, fatigue, blurred vision, ketoacidosis in some cases

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9
Q

What are the symptoms of DM 2?

A

Obesity, fatigue, polyuria and polydipsia, though patients are often asymptomatic; IFG and IGT can be detected and precede the onset

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10
Q

What are the normal fasting plasma glucose, 2 hour peak postprandial plasma glucose, and HbA1c levels?

A
  1. <100 mg/dL
  2. <140 mg/dL
  3. <6.0%
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11
Q

What are the pre-diabetic fasting plasma glucose, 2 hour peak postprandial plasma glucose, and HbA1c levels?

A
  1. 100-125 mg/dL
  2. 140-199 mg/dL
  3. n/a
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12
Q

What are the diabetic fasting plasma glucose, 2 hour peak postprandial plasma glucose, and HbA1c levels?

A
  1. > 126 mg/dL
  2. > 200 mg/dL
  3. > 6.5%
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13
Q

What are the pretreatment goal fasting plasma glucose, 2 hour peak postprandial plasma glucose, and HbA1c levels?

A
  1. 90-130 mg/dL
  2. <180 mg/dL
  3. <6.5%
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14
Q

What is the major side effect of intensive therapy to treat DM?

A

Increased risk of hypoglycemia

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15
Q

What is the only treatment for DM 1?

A

Insulin replacement therapy; required for both glycemic control and survival

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16
Q

What is the goal of insulin replacement therapy?

A

Replicate the normal physiological production of insulin by the pancreas

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17
Q

What are the two types of insulin produced physiologically in the pancreas?

A
  1. Basal insulin (produced under fasting conditions)

2. Postprandial insulin (produced in response to each meal)

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18
Q

Describe the MOA of insulin.

A

Insulin acts through its plasma membrane cell surface tyrosine kinase receptor.

  1. Inhibits secretion of glucagon in the liver (inhibits hepatic glucose production)
  2. Stimulates glucose uptake via upregulation of the GLUT4 glucose transporter in the muscle and adipose tissue
  3. Promotes amino acid uptake and protein synthesis in muscle (blocks flow of gluconeogenic precursors to the liver)
  4. Inhibits lipolysis and promotes TG storage in adipose tissue (also prevents flow of gluconeogenic precursors to the liver and reduces energy substrate for gluconeogenesis)
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19
Q

List the 4 categories of commercially-available insulin preparations.

A
  1. Rapid-acting
  2. Regular
  3. Intermediate acting
  4. Long-acting
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20
Q

List the rapid-acting insulin preparations.

A
  1. Insulin aspart
  2. Insulin lispro
  3. Insulin glulisine
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21
Q

List the intermediate-acting insulin preparations.

A
  1. NPH insulin (isophane)
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22
Q

List the long-acting insulin preparations.

A
  1. Insulin glargine

2. Insuline detmir

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23
Q

Compare the onset of the 4 categories of commercially-available insulin preparations.

A
  1. Rapid-acting: 5-15 minutes
  2. Regular: 30-60 minutes
  3. Intermediate acting: 1.5-2 hours
  4. Long-acting: ~2 hours
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24
Q

Compare the peak of the 4 categories of commercially-available insulin preparations.

A
  1. Rapid-acting - 45-75 minutes
  2. Regular - 2-4 hours
  3. Intermediate acting - 6-10 hours
  4. Long-acting - no peak
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25
Q

Compare the duration of the 4 categories of commercially-available insulin preparations.

A
  1. Rapid-acting - 2-4 hours
  2. Regular - 6-8 hours
  3. Intermediate acting - 16-24 hours
  4. Long-acting - 20-24 hours (glargine) and 6-24 hours (detmir)
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26
Q

How is rapid-acting insulin used?

A

For meals or acute hyperglycemia; can be injected immediately before meals

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27
Q

How is regular insulin used?

A

For meals or acute hyperglycemia; needs to be injected 30-45 minutes prior to a meal

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28
Q

How is intermediate-acting insulin used?

A

Provides basal insulin and overnight coverage

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29
Q

How is long-acting insulin used?

A

Provides basal insulin and overnight coverage

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30
Q

How is insulin administered?

A

Subcutaneously by either intermittent injections or continuous infusion

  1. Insulin syringe
  2. Insulin pen (pre-filled disposable cartridge)
  3. Insulin pump (computer delivers precise amounts of fast-acting insulin throughout the day)
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31
Q

What are the sites of injection for insulin and why should they be continuously rotated?

A

Upper arms, thighs, abdomen, buttocks

Avoid lipdystrophy

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32
Q

What is given in conventional insulin therapy?

A

Twice daily injections of pre-mixed intermediate insulin (NPH) + regular insulin; typically 50-75% NPH and 25-50% regular/fast-acting insulin

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33
Q

Discuss the risks of conventional insulin therapy.

A

Risk of hypoglycemia when midday NPH insulin spikes (depending on lunch)

Risk of nocturnal hypoglycemia when evening NPH insulin spikes (depending on dinner)

Risk of hyperglycemia due to the dawn phenomenon (increased blood glucose due to cortisol burst in the morning)

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34
Q

Describe intensive insulin therapy.

A

Once/twice daily basal insulin (NPH or glargine) to lower fasting glucose and pre-meal bolus of rapid/fast-acting insulin to control post-prandial glucose; provides a more physiological profile

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35
Q

How is the dose of a pre-meal bolus determined in intensive insulin therapy?

A
  1. Blood glucose levels
  2. Size and composition of meal (amount of carbs)
  3. Degree of anticipated physical activity
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36
Q

What are the drawbacks of intensive therapy?

A
  1. Patient commitment and effort required
  2. Higher cost
  3. Increased risk of AE
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37
Q

What is hypoglycemia?

A

Blood glucose level <60 mg/dL; potentially fatal if not promptly treated (caused by lack of glucose available for the brain)

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38
Q

What are the symptoms of mild hypoglycemia?

A

Tremor, palpitations, sweating, intense hunger

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39
Q

What are the symptoms of moderate hypoglycemia?

A

Headache, mood changes and irritability, decreased attention, drowsiness, patients may require assistance to help themselves

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40
Q

What is the treatment for moderate hypoglycemia?

A

Oral dose of a simple carbohydrate

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41
Q

What are the symptoms of severe hypoglycemia?

A

Unresponsiveness, unconsciousness, convulsions, prolonged severe hypoglycemia can result in death, require assistance for treatment

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42
Q

What is the treatment for severe hypoglycemia?

A

IV glucose or glucagon (stimulates release of glucose from the liver)

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43
Q

Discuss the diet and exercise interventions to treat DM2?

A

Decrease: refined sugar, fat to <30% of energy intake, saturated fat to <10% of energy intake

Increase: complex carbs (low glycemic index), fiber

Exercise 30 minutes/day

Decrease weight by 5%

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44
Q

What are the effects of the above diet and exercise interventions on DM2?

A

Improved insulin sensitivity, reduced blood glucose, reduced BP, improved lipid profile, increased longevity

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45
Q

What are the effects of bariatric surgery on DM2?

A

Can restore normoglycemia in people with DM2 who are obese - decreases visceral obesity, improves pancreatic function, and has a favorable effect on gut hormones

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46
Q

List the 7 categories of drugs available to treat DM2.

A
  1. Insulin sensitizers
  2. Insulin secretagogues
  3. Incretin mimetics and modulators
  4. Inhibitors of carbohydrate digestion
  5. Other
  6. Insulin
  7. Amylin homolog
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47
Q

List the insulin sensitizers.

A
  1. Biguanides - Metformin

2. Thiazolidinediones - Pioglitazone and Rosiglitazone

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48
Q

List the insulin secretagogues.

A
  1. Sulfonylureas - Chlorpropamide, Tolbutamide, Glimepiride, Glyburide, Glipizide
  2. Meglitinides - Repaglinide, Nateglinide
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49
Q

List the incretin mimetics and modulators.

A
  1. GLP-1 homologus - Exenatide, Liraglutide

2. DPP-IV inhibitors - Sitagliptin, Saxagliptin

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50
Q

List the inhibitors of carbohydrate digestion.

A
  1. Alpha-glucosidase inhibitors - Acarbose, Miglitol
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51
Q

List the other drugs available to treat DM2 (newly approved and other)

A
  1. SGLT2 inhibitors - Canagliflozin and Dapagliflozin
  2. Bromocriptine
  3. Bile acid-binding resin - Colesevelam
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52
Q

List the amylin homolog.

A

Pramlintide

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53
Q

Which categories of DM2 drugs are parenteral?

A
  1. GLP-1 homologs
  2. Insulin
  3. Amylin homolog
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54
Q

True or false - insulin sensitizers are dependent upon the presence of insulin for their effects.

A

True

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55
Q

What is the recommended initial drug of choice in treatment of all patients with DM2 unable to control glucose levels with diet and exercise along?

A

Metformin

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56
Q

Describe the effects of metformin.

A

Primarily lowers fating plasma glucose - decreases hepatic gluconeogenesis and increases insulin sensitivity/glucose uptake in muscle, liver, and adipose

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57
Q

By what percentage does metformin lower the HbA1c?

A

1.5-2.0%

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58
Q

What are the advantages of metformin?

A
  1. Does not cause hypoglycemia
  2. Not associated with weight gain
  3. Improves lipid profiles
  4. Decreases frequency of MI, diabetes-related death, and all cause mortality in patients with DM2
59
Q

What is the MOA of metformin?

A

Inhibits complex I of mitochondrial oxidative phosphorylation (first step in the electron transport chain), leading to an increase in AMP. This antagonizes glucagon by inhibiting AC activity (needed for hepatic gluconeogenesis) and induces the activation of the AMP-dependent protein kinase (AMPK).

60
Q

What are the effects of increased AMPK on muscle, liver, adipose, and brain?

A

Muscle: increased insulin sensitivity and glucose uptake
Liver: decreased hepatic gluconeogenesis, triglyceride/cholesterol synthesis, increased FA oxidation
Muscle and liver - decreased plasma glucose

Adipose: increased insulin sensitivity, glucose uptake, lipogenesis, decreased lipolysis
Liver and adipose - decreased FFA leads to decreased insulin resistance

Brain: decreased food intake

61
Q

What are the AE of metformin?

A

Generally well-tolerated; most common - GI (metallic/fishy taste), nausea, diarrhea

Inhibits absorption of B12, but rarely causes megaloblastic anemia

62
Q

What is a rare but serious AE of metformin?

A

Lactic acidosis - rare, but potentially fatal

Acidification of the blood caused by a build-up of lactic acid; mostly associated with use of metofrmin in specific high risk patients (renal/liver insufficiency, CHF, MI, hypoxic states)

63
Q

What are symptoms of lactic acidosis?

A

Deep and rapid breathing, vomiting, abdominal pain, severe weakening of muscles in the legs and arms

64
Q

Describe how metformin may cause lactic acidosis.

A

Lactate is normally metabolized and cleared via the liver and kidney. Metformin blocks gluconeogenesis in the liver, backing up lactate (increases its levels), which blocks renal clearance, leading to lactic acidosis.

65
Q

What are the contraindications of metformin?

A
  1. Women who are pregnant or lactating
  2. Patients with impaired renal and liver function
  3. Elderly (>80 y/o) - renal insufficiency
  4. Patients taking iodinated contrast agent due to potential for contrast agent-induced acute renal failure
  5. Any condition pre-disposing to lactic acidosis - impaired renal function, liver function/alcohol abuse, CHF requiring drug therapy, MI, shock and/or septicemia, serious acute illness, hypoxic or ischemic states
66
Q

What are the Thiazolidinediones (“Glitazones”)?

A

Insulin sensitizers that increase the sensitivity of adipose tissue, skeletal muscle, and liver to the effects of endogenous insulin

67
Q

What is the MOA of Thiazolidinediones?

A

Agonists of the peroxisome proliferator-activated receptor-gamma transcription factor (PPAR-gamma); the PPAR-gamma genes are expressed in adipose tissue, skeletal muscle, liver, heart, and macrophages; activation of the TF leads to increased insulin sensitivity and decreased plasma glucose levels

68
Q

How is insulin sensitivity increased by PPAR-gamma-dependent gene transcription?

A
  1. Increased GLUT4 (increases glucose uptake)
  2. Increased adiponectin (increases systemic insulin responsiveness)
  3. Increased genes involved in FFA uptake/oxidation
  4. Adipose remodeling - increased SubQ adipose (insulin sensitive) and decreased visceral adipose (insulin resistant)
  5. Inhibition of TNF-alpha and resistin (cytokines that promote insulin resistance)
69
Q

How is fasting glucose decreased by PPAR-gamma-dependent gene transcription?

A

Inhibition of hepatic gluconeogenic genes leads to decreased hepatic glucose output and decreased fasting glucose

70
Q

What are the indications of Thiazolidinediones?

A

Monotherapy or in combination with either metforming, sulfonylureas, or insulin to treat DM2

71
Q

Describe the effects of Thiazolidinediones.

A

Decreases fasting blood glucose with moderate effects on postprandial glucose

72
Q

By what percentage do Thiazolidinediones lower the HbA1c?

A

0.5-1.4%

73
Q

What are the AE of Thiazolidinediones?

A
  1. Weight gain (mostly subQ fat)
  2. Fluid retention resulting in peripheral edema (more common w/concurrent insulin use, increases expression of Na+ channel in CT, increases reabsorption, increases risk of heart failure)
  3. Increased bone fracture risk in women (decreases osteoblastogenesis/increases osteoclastogenesis)
  4. Increased risk of bladder cancer
  5. Hepatotoxicity
74
Q

What are the contraindications of Thiazolidinediones?

A
  1. Liver disease
  2. Heart failure
  3. Pregnancy
75
Q

Compare the two classes of Insulin Secretagogues (Sulfonylureas and Meglitinies).

A

Sulfonylureas - slower onset, long-half lives, long duration of effect, primarily affect fasting glucose

Meglitinides - rapid onset, short half-lives, short duration of effect, primarily affect postprandial glucose

76
Q

What are Sulfonylureas?

A

Oral drugs that lower blood glucose levels by stimulating pancreatic beta cells to secrete insulin

77
Q

What is the MOA of Sulfonylureas?

A

Normally, high glucose enters the beta cells via GLUT2, where it undergoes glycolysis and produces ATP via the Krebs cycle. ATP inhibits the Kir6.2 K+ channel, leading to increased intracellular K+; this causes membrane depolarization and opening of voltage-gated Ca2+ channels, which enters the cell and causes secretion of insulin granules.

Sulfonylureas mimic the ATP by blocking the K+ channel via its Sur1 subunit.

78
Q

What are the uses of Sulfonylureas?

A
  1. Long duration of glucose lowering effect (16-24 hours) - stimulate insulin production in the absence of glucose, effect is sustained for 24 hours, principle effect - reduces fasting plasma glucose
  2. Used to control hyperglycemia in DM2 due to elevated FPG
79
Q

What are the effects of Sulfonylureas on FPG and HbA1C?

A

Reduces FPG by 50-70 mg/dL and HbA1c by ~1.5-2.0%

80
Q

Upon what does sulfonylurea activity depend?

A

Functional beta cells

81
Q

What are the AE of Sulfonylureas?

A

Hypoglycemia in patients with impaired renal and hepatic function and the elderly; weight gain

82
Q

All sulfonylureas are metabolized in the ___ and excreted by the ___.

A

Liver; kidney

83
Q

Discuss the half-life and metabolism of Glyburide and Glimepiride.

A

Longer half-life (20-24+ hours), active metabolites with reduced activity, increased drug concentration and drug activity in renal/hepatic insufficiency

84
Q

Discuss the half-life and metabolism of Glipizide?

A

Short acting (14-16 hours), inactive metabolites, may be safer for patients with renal insufficiency

85
Q

What are the contraindications of Sulfonylureas?

A
  1. Elderly patients and those with impaired renal/liver function
  2. Patients with DM1
  3. Pregnant or lactating women
  4. Patients with sulfa allergies
86
Q

Which Sulfonylurea drug is preferred in the presence of renal insufficiency and in the elderly? What is an alternative in the presence of renal insufficiency?

A

Glipizide; Repaglinide

87
Q

Why do Sulfonylureas interact with many drugs?

A

They are highly protein bound

88
Q

What are Meglitinides?

A

Short-acting glucose-lowering oral drugs that are structurally distinct from sulfonylureas but act similarly to lower blood glucose levels by stimulating pancreatic beta cells to secrete insulin

89
Q

What is the MOA of Meglitinides?

A

Same as sulfonylureas, just bind to a different region of the SUR1 subunit

90
Q

What are the important differences of Meglitinides when compared to Sulfonylureas?

A

Effect is more rapid, shorter duration, glucose-dependent

91
Q

Discuss the indications for Meglitinides.

A

Rapidly absorbed/fast-acting glucose-lowering drug used to reduce hyperglycemia in DM2; should be taken prior to, or with, meals; effective at controlling postprandial glucose elevation; often used in combination with drugs that primarily affect fasting plasma glucose

92
Q

What is the effect of Meglitinides on the HbA1c?

A

1.0-1.5% reduction

93
Q

Compare the effects of Nateglinide and Repaglinide.

A

Nateglinide - glucose-dependent, rapidly reversed, affects primarily postprandial glucose

Repaglinide - effect is more prolonged, affects both postprandial and fasting glucose

94
Q

Compare the PK of Repaglinide and Nateglinide.

A

Repaglinide - 100% metabolized in the liver (3A4) to inactive metabolites; 90% fecal elimination

Nateglinide - 80% metabolized in liver (2C9/3A4) to inactive metabolites; 80% of metabolites and unchanged drug eliminated in urine, 20% in feces, but does NOT require dose adjustment in renal insufficiency

95
Q

What are the AE of Meglitinides?

A
  1. Hypoglycemia (less frequent than sulfonylureas)

2. Weight gain (similar to sulfonylureas)

96
Q

What are the contraindications of Meglitinides?

A

Liver disease and pregnancy

97
Q

What is the incretin effect?

A

The observation that plasma insulin levels induced in response to oral glucose are greater than those induced by IV glucose.

98
Q

What mediates the inretin effect?

A

Glucose-induced production of specific polypeptide hormone factors produced by GI tract cells; they act on the beta cells to potentiate glucose-induced insulin production

99
Q

What happens to the incretin effect in patients with DM2?

A

Reduced

100
Q

Exenatide and Liraglutide are stable analogs of Glucagon-like peptide-1 (GLP-1) - what is this?

A

Short-lived hormone made by the L cells of the small intestine that mediates the incretin effect on plasma insulin levels

101
Q

What is the MOA of Exenatide?

A

Binds to the GLP-1 receptor on beta cells and potentiates glucose-induced insulin secretion when levels are high (when glucose levels fall, its effect on insulin secretion diminishes, so there is little risk of hypoglycemia)

Suppresses hepatic glucose production by inhibiting pancreatic production of glucagon

Promotes pancreatc beta cell survival

Slow gastric emptying (reduces glucose absorption)

Increases satiety (reduces food intake)

102
Q

What are the indications of Exenatide/Liraglutide?

A

Alternative to starting insulin in patients with DM2 who have not achieved glycemic control with other medications

Acts to reduce both fasting glucose and post-prandial glucose

Also promotes modest weight loss due to satiety

103
Q

How is Exantide/Liraglutide administered?

A

Injected SubQ once/twice daily (new once weekly formulation available)

104
Q

What is the effect of Exenatide/Liraglutide on fasting and postprandial glucose?

A

Reduces HbA1c by 0.5-0.7%

105
Q

What are the AE of Exenatide/Liraglutide?

A

Frequent N/V and diarrhea

106
Q

What are the DPP-IV inhibitors?

A

Oral medications taken once daily, rapidly absorbed, peak within 1-4 hours, effective for 24 hours; decreases both fasting and postprandial glucose

Monotherapy or adjunctive therapy for DM 2 with metformin or a thizolidinedione

107
Q

What are the effects of DDP-IV inhibitors on HbA1c?

A

0.48-0.61%

108
Q

What is the MOA of DDP-IV inhibitors?

A

Inhibition of DDP-IV (breaks down GLP-1 normally)

109
Q

What are the AE of DDP-IV inhibitors?

A

Long-term consequences not known

110
Q

What are alpha-glucosidase inhibitors?

A

Drugs that reduce postprandial blood glucose levels by inhibiting the digestion of polysaccharides in the SI

111
Q

What is the MOA of alpha-glucosidase inhibitors?

A

Inhibit alpha-glucosidase, the enzyme lining the SI brush border responsible for the hydrolysis of dietary carbohydrates, which delays the absorption of glucose and other monosaccharides, leading to decreased absorbed glucose

112
Q

What are the indications of alpha-glucosidase inhibitors?

A

Control of postprandial hyperglycemia (should be taken with each meal); does not cause hypoglycemia; not first line

113
Q

What is the effect of alpha-glucosidase inhibitors?

A

0.5-0.8%

114
Q

What are the AE of alpha-glucosidase inhibitors?

A

GI side effects (abdominal pain, flatulence)

Does not cause hypoglycemia, but can increase it when given with either a sulfonylurea or insulin

115
Q

What are the contraindications of alpha-glucosidase inhibitors?

A

Chronic intestinal disease
IBD
Colonic ulceration or intestinal obstruction

116
Q

What are SGLT2 inhibitors?

A

Drugs that reduce hyperglycemia by promoting glucose excretion in the urine

117
Q

What is the MOA of SGLT2 inhibitors?

A

Inhibition of SGLT2 activity in the S1 segment of the proximal tubule prevents the normal process of glucose reabsorption, leading to excretion of glucose in the urine

118
Q

What are the indications of SGLT2 inhibitors?

A

Improving glycemic control in DM2 (mono or combo)

Decreases body weight

Decreases BP (water eliminated by increased osmotic diuresis)

119
Q

What is the effect of SGLT2 inhibitors on HbA1c?

A

0.5-0.9% reduction

120
Q

What are the AE of SGLT2 inhibitors?

A
  1. UTI and genital mycotic infections
  2. Thirst/dehydration
  3. Hypotension
  4. Increased LDL
  5. Hyperkalemia (espeically patients taking medications that interfere with K+ excretion like K+ sparing diuretics)
121
Q

What are the contraindications of SGLT2 inhibitors?

A

Renal impairment

122
Q

What is Bromocriptine?

A

Sympatholytic D2 receptor agonist; thought to act on the CNS to normalize the decreased AM dopamine levels present in DM2 patients

123
Q

What is the effect of Bromocriptine on HbA1c?

A

~0.5% reduction

124
Q

In diabetes, early morning hypothalamic dopamine levels decrease. What are the effects of this?

A

Increased hypothalamic SNS, hepatic gluconeogenesis, lipolysis/FFA, lipogenesis/TG

Causes glucose intolerance, insulin resistance, dyslipidemia, increased risk of CVD

125
Q

What are the effects of treatment with Bromocriptine in the early morning (must take within 2 hours of waking)?

A

Increased hypothalamic dopamine levels leads to decreased hypothalamic SNS, hepatic gluconeogenesis, lipolysis/FFA, and lipogenesis/TG

Causes glucose tolerance, increased insulin sensitivity, decreased serum FFA, decreased vascular pathology

126
Q

What is Colesevelam?

A

LDL-lowering drug used as an adjunct to anti-diabetic therapy to reduce blood glucose levels by indirectly increasing GLP-1 expression

127
Q

What is the MOA of Colesevelam?

A

Binds bile acids in the SI, forming insoluble complexes and preventing bile acid reabsorption; the complexes enter the large colon, where they trigger the TGR5 GPCR to stimulate GLP-1 secretion

128
Q

What are the indications for Colesevelam?

A

Add on therapy to metformin, sulfonylureas, or insulin; not first line; useful in patients who also exhibit elevated LDL-cholesterol levels

129
Q

What is the effect of Colesevelam on HbA1c?

A

~0.5% reduction

130
Q

What is the most efective medication at lowering hyperglycemia?

A

Inuslin

131
Q

When should insulin be considered as an initial therapy?

A

When patients present with HbA1c >10%; anyone with recent onset of diabetes accompanied by significant weight loss, polyuria, and polydipsia (late onset type 1)

132
Q

How is insulin used in DM2?

A

Second line in patients with HbA1c >8.5%

Initial therapy should be a basal insulin 1-2x/day to lower FPG levels by inhibiting hepatic gluconeogenesis; if necessary, regular/rapid-acting insulin can be added before meals to control postprandial glucose excursions

133
Q

Which type of diabetes requires more insulin?

A

DM 2 - due to insulin resistance

134
Q

What is Pramlintide?

A

Synthetic analog of human amylin

135
Q

What is amylin?

A

An endogenous polypeptide hormone that is co-secreted with insulin and contributes to postprandial glucose control; it is absent in patients with diabetes

136
Q

What is the MOA of Pamlintide?

A

Inhibits hepatic gluconeogeneesis, postprandial glucagon, slows gastric emptying, and increases satiety; primarily acts to decrease postprandial elevations due to its short duration of action

137
Q

What are the indications of Pramlintide?

A

Adjunct therapy in DM1 or 2 for patients using insulin but who have not achieved adequate glycemic control; provides postprandial glucose control and need to be injected in parallel to insulin prior to each meal

Effects are additive to insulin, reduces amount of short/rapid-acting insulin required

138
Q

What is the effect of Pramlintide on HbA1c?

A

0.5-0.7% reduction

139
Q

What are the AE of Pramlintide?

A

N/V, anorexia, headache

Increases risk of severe hypoglycemia with insulin

140
Q

After an initial diagnosis, how should DM2 be treated?

A

Therapeutic lifestyle change, diet and exercise; improves weight loss, BP, lipid profile

141
Q

If HbA1c remains > 7%, what is the next step in treatment?

A

Metformin (safe, promotes weight loss, improves lipid profile, decreases risk of CVD)

142
Q

If HbA1c remains > 7% after metformin treatment, what are the next options?

A
  1. +Sulfonylurea (least expensive, but increased risk of hypo)
  2. +Thiazolidinedione (low risk of hypo, increased risk of CVD)
  3. +Exenatide (may be beneficial in patients who are overweight)
  4. +Insulin (most effective especially if HbA1c >8.5%)
143
Q

If glycemic goal is still not achieved, what can be done?

A

Add a third medication
Add insulin
Intensify insulin regimen

PT 2 (15 decks)

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