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Endocrinology > Diabetes Pharm Part 1 > Flashcards

Diabetes Pharm Part 1 Flashcards

1
Q

What are the oral glucose lowering meds?

7

A
  1. Biguanides
  2. Sulfonylureas
  3. Meglitinieds
  4. TZDs
  5. ∂-glucosidase inhibitors
  6. DPP-4 inhibitors
  7. SGLT2 inhibitors
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2
Q

What are the non-insulin injectables?

2

A
  1. GLP-1 receptor agonists

2. Amylin mimetics

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3
Q

What are the types of insulin?

4

A

Short
Rapid
Intermediate
Basal

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4
Q

What is the brand names for Biguanides?

3

A
  1. Metformin (Glucophage)
  2. Metformin/Glyburide (Glucovance)
  3. Metformin/Glipizide (Metaglip)
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5
Q

Biguanides MOA?

A

inhibits hepatic glucose production (gluconeogenesis and glycogenolysis) and improves insulin sensitivity

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6
Q

7 Reasons why metformin is first line therapy

9

A
  1. Glycemic efficacy
    - -Decreases A1C by 1.5%
  2. No weight gain
    - -May lose weight or at least stabilize weight
  3. No hypoglycemia
  4. May help improve lipids
  5. Well tolerated
  6. Favorable cost
  7. Pregnancy Cat B
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7
Q

Side effects of Biguanides?

Usually does not cause what?

Rarely can cause what?
(what increases this risk?)2

A

GI side effects
Diarrhea, nausea, vomiting, flatulence
Symptoms tend to decrease over time
Start with a low dose and titrate up

Does not usually cause hypoglycemia

Can rarely cause lactic acidosis
Increased risk if on glucocorticoids or with ETOH

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8
Q

Contraindications for metformin

5

A
  1. Alcoholics
  2. Discontinue temporarily if receiving iodinated contrast
  3. Renal dysfunction
  4. Serum creatinine ≥1.5 mg/dL in males or ≥1.4 mg/dL in females)
  5. Abnormal creatinine clearance from any cause
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9
Q

What can cause abnormal creatine clearance?

4

A

including

  1. shock,
  2. acute myocardial infarction, or
  3. septicemia;
  4. acute or chronic metabolic acidosis with or without coma (including diabetic ketoacidosis)
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10
Q

WHat is the metformin black box warning?

A
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11
Q

The risk of lactic acidosis is increased in who?

5

A

The risk is increased in patients with acute

  1. congestive heart failure,
  2. dehydration,
  3. excessive alcohol intake, 4. hepatic or renal impairment, or
  4. sepsis.
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12
Q

What are the signs and symtpoms (labs too) of lactic acidosis? 4

What should we do if we see these symptoms?

A
  1. Symptoms may be nonspecific (eg, abdominal distress, malaise, myalgia, respiratory distress, somnolence);
  2. low pH,
  3. increased anion gap and 4. elevated blood lactate may be observed.

Discontinue immediately if acidosis is suspected.

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13
Q

If on contrast for procedure what should we do?

A

Stop metformin two days before and start them 2 days after

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14
Q

In what pts should we suspect lactic acidosis?

What symtpoms would this show? 3

A

Lactic acidosis should be suspected in any patient with diabetes receiving metformin with evidence of acidosis but without evidence of ketoacidosis.

dehydration, sepsis, hypoxemia

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15
Q

The risk of impairment increases with what?

A

the degree of renal imapiment

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16
Q

What are the Sulfonylureas?

A
  1. Glipizide(Glucotrol) (Glucotrol XL)
  2. Glyburide(Diabeta) (Micronase) (Glynase)
  3. Glimepiride (Amaryl)
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17
Q

Never use the first gen?

A

Sulfonylureas

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18
Q

Sulfonylureas MOA?

2

A
  1. Bind to beta cell receptors and cause ATP-dependent potassium channels to close
  2. The calcium channels then open = ↑ cytoplasmic calcium = ↑ insulin release from pancreas
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19
Q

Sulfonylureas correct derangements of metabolism of what?

3

A

Carbohydrates, lipid and proteins

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20
Q

What are the 2nd generation Sulfonylureas?
3

Onset usually within how much time and lasts how long?

A

2nd Generation Agents
Glimepiride (Amaryl)
Glipizide (Glucotrol)
Gluyburide (Micronase)

Onset usually within 1-3 hours and lasts up to 24 hours
Start low, titrate up slow

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21
Q

What is the major risk of Sulfonylureas and who has an increased risk with this (4)?

A

Major risk of hypoglycemia in the following patients

  1. Elderly,
  2. ETOH abuse,
  3. poor nutrition,
  4. renal insufficiency
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22
Q

Do Sulfonylureas increase insulin sensitivity?

What happens to the effectveness over time?

weight loss or weight gain?

A

no

descrease

Causes weight gain over 2-3 kg

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23
Q

IF a pt has hypoglycemic episodes and nothing has changed what do we need to rule out?

A

renal failure

from medication or something else

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24
Q

Sulfonylureas Contraindications

3

A
  1. Sulfa allergy
  2. High risk for hypoglycemia
  3. Ketoacidosis
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25
Q

Ideal patients for sulfonylureas

6

A
  1. Duration of disease less than 5 years
  2. No history of prior insulin therapy
    (or good control on less than 40 U insulin per day)
  3. Close to normal body weight
  4. Fasting glucose less than 180 mg/dL
  5. No history of sulfa allergy
  6. Avoid in persons (like the elderly) who are at high risk for hypoglycemia
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26
Q

Notable differences in drugs:

Which drug has less incidence of hypoglycemia compared to longer duration of action meds and has a 14-16 hr duration?

Which drugs last for 20-24h?

Which last for more than 24 hrs?

A

Glipizide(Glucotrol)(Glucotrol XL)

Glyburide(Diabeta)(Micronase)(Glynase)

Glimepiride (Amaryl)

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27
Q

WHat are the Thiazolidinediones aka TZDs?

2

A

Rosiglitazone (Avandia)

Pioglitazone (Actos)

28
Q

Thiazolidinediones aka TZDs MOA?

What may it decrease?

What does it improve?

A

Increase insulin sensitivity in skeletal muscle and fat by binding to the nuclear steroid hormone receptor PPAR-gamma thereby decreasing peripheral insulin resistance

May decrease hepatic glucose production at higher doses

Improvement of endothelial function and decreases albumin excretion

29
Q

How do we usually use TZDs?

A

Usually used as add-on therapy down the line in patients who have failed or are unable to tolerate other therapies

30
Q

Can TZDs cause hypoglycemia?

What about use with insulin or sulfonylureas?

A

MOA is to increase insulin sensitivity so on it’s own would not cause hypoglycemia because it does not increase insulin secretion

YES! Hypoglycemia can occur with the improvement of insulin sensitivity in patients or supplemental insulin or SUs

31
Q

Thiazolidinediones: Major Adverse effects

5

A
  1. Weight gain
  2. Fluid retention
  3. Hepatotoxicity
  4. Increasing evidence of causing decreased bone density
  5. Cardiovascular effects (think Rosiglitazone):
32
Q

What lab monitoring tests should we do for TZDs?

A

acquire baseline liver functions, every 2 months for the first 12 months, then periodically thereafter

33
Q

Why does TZDs cause cardiovascular effects?

A

Elevates LDL and HDL, may increase risk of cardiovascular events and heart failure

34
Q

TZDs Black box warning

A

Congestive heart failure: Thiazolidinediones, including rosiglitazone, cause or exacerbate congestive heart failure (CHF) in some patients.

After initiation of rosiglitazone and after dose increases, observe patients carefully for signs and symptoms of heart failure (including excessive, rapid weight gain; dyspnea; and/or edema).

If these signs and symptoms develop, manage the heart failure according to current standards of care. Furthermore, consider discontinuation or dose reduction of rosiglitazone.

***DOnt’t use it if the pt has symptomatic heart failure. monitor very closely if they arent symptomatic

35
Q

WHo is Rosiglitazone not recommended in?

A

not recommended in patients with symptomatic heart failure. Initiation of rosiglitazone in patients with established New York Heart Association (NYHA) class III or IV heart failure is contraindicated.

36
Q

Black box warning for Rosiglitazone?

A

Myocardial infarction

37
Q

What are the Alpha-glucosidase inhibitors

2

A

Acarbose (Precose)

Miglitol (Glyset)

38
Q

Alpha-glucosidase inhibitors MOA?

A

Slows the absorption of carbohydrates from the intestines by interfering with alpha-glucosidase, an enzyme found on the brush border of the intestine necessary for the absorption of starch and disaccharides

39
Q

Alpha-glucosidase inhibitors therpeutic uses?

A

Most useful in patients with postprandial hyperglycemia and patients with high A1C levels and poor dietary adherence

40
Q

Alpha-glucosidase inhibitors therpeutic major adverse affects?

Alpha-glucosidase inhibitors contraindications?

A

GI effects including increased intestinal gas, flatulence, diarrhea, and abdominal distention

Patients with GI motility disorders, cirrhosis, and diseases of the bowel (e.g. inflammatory bowel disease, absorptive disorders)

41
Q

How to dose Alpha-glucosidase inhibitors?
2

Monitoring? 2

A
  1. Dose with the first bite of the meal (TID)
  2. Start at the lowest dose and titrate up every 1-2 months as needed
  3. 1 hour post prandial glucose measurement will help assess the response during titration of drug
  4. Monitoring: LFTs q 3 months the first year of therapy
42
Q

What are the Meglitinides?
2

MOA?

A

Nateglinide (Starlix)
Repaglinide (Prandin)

similar to sulfonylureas, increases insulin secretion from the pancreas
Lowers post prandial glucose levels but do not change fasting plasma glucose levels

43
Q

Uses of meglitinides

4

A
  1. Alternative for patients who are candidates for SUs but have a sulfa allergy
  2. Possibly less risk of hypoglycemia (can consider this an alternative if hypoglycemia on SUs)
  3. Good for patients with erratic eating schedules (take with meals)
    Dose up to 4 times a day and only take if they eat
  4. For patients with acceptable fasting plasma glucose levels and elevated post prandial levels
44
Q

Adverse effects of Nateglinide

Adverse effects of Repaglinide

Two other side effects?

A

– may cause severe hypoglycemia in patients with renal insufficiency

– no dose adjustments needed with renal insufficiency

  1. Weight gain can be an issue
  2. Drug interactions with drugs metabolized through the CYP450 3A4 pathway

Less potent/less episodes of hypoglycemia

45
Q

The Dipeptidyl Peptidase-4 Inhibitors are?
4

MOA?

A

Sitagliptin (Januvia)
Saxtagliptin (Onglyza)
Linagliptin (Tradjenta)
Alogliptin (Nesina)

inhibits the enzyme that breaks down endogenous GLP-1 (incretin/part of feedback of insulin going back into the cell) thereby allowing increased amounts

(prolongs the amount of timeyour endogenous GLP-1 hangs around)

46
Q

Dipeptidyl Peptidase-4 Inhibitors Contraindications/Interactions? 3

A
  1. Caution with renal impairment
  2. Sitaliptin contraindicated with a history of pancreatitis
  3. Drug interactions
47
Q

Saxtagliptin is a potent CYP3A4/5 inhibitor so avoid with what?
3

A
  1. ketoconazole,
  2. diltiazem and
  3. erythromycin
48
Q

Major side effects
of Dipeptidyl Peptidase-4 Inhibitors?
7

A
  1. Upper respiratory infections,
  2. UTI and
  3. HA
  4. Hypoglycemia when given with SU
  5. Hypersensitivity reactions
  6. Elevated liver enzymes
  7. Pancreatitis
49
Q

What are the SGLT2 inhibitors?

3

A

Canagliflozin (Invokana)
Dapagliflozin (Farxiga)
Empagliflozin (Jardiance)

50
Q

SGLT2 inhibits what?

What is SGLT2?

Why does this drug work well on T2DM pts?

MOA?

What does the GFR need to be for this med?

A

proximal nephron

a transporter in the renal tubule where 90% of glucose resorption occurs

T2DM pts have an upregulation of SGLT2 and have increased renal glucose reabsorption

These meds work by blocking these SGLT2 sites which decreases glucose reabsorption in the kidney therefore causing glucosuria

GFR needs to be at least 45 mL/min

51
Q

Benefits of SGLT2?

5

A
  1. No hypoglycemia
  2. Promotes weight loss
  3. Effective at all stages of DM
  4. Can take with other DM therapies and may have a role in T1DM
  5. Targets the kidney so minimal risk for off target adverse effects
52
Q

Side effects of SGLT2?

8

A
  1. GU infections
  2. Polyuria
  3. Dehydration,
  4. dizziness, low BP
  5. Increased LDL (5-7%)
  6. Transient increase in creatinine
  7. Caution for hypoglycemia if used with insulin or SUs
  8. Cost is about $400/mo for Invokana
53
Q

What are the GLP-1Receptor Agonists?

4

A

Exenatide (Byetta)
Liraglutide (Victoza)
Albiglutide (Tanzeum)
Dulaglutide (Trulicity)

54
Q

Background Info: Exendin-4 is a naturally occurring component of the what?

What makes it more effective
?

A

Gila monster (Heloderma suspectum) saliva, and shares 53 percent sequence identity with GLP-1.

Here’s the key… it is resistant to DPP-IV degradation and therefore exhibits a prolonged half-life

55
Q

Incretin Mimetics (GLP-1 Analog) is dosed how?

common side effects?

Hypoglycemic effects?

Weight loss or weight gain?

A

Requires two subq injections daily prior to meals

Common side effect is nausea (but mild to moderate intensity and wanes over time)

Glucose dependent effects on insulin and therefore NO hypoglycemia
—Reduces A1C

Promotes weight loss

EXPENSIVE

56
Q

What is one thing we need to know about Exanitide (Byetta)?

How does it affect gastric emptying time?

Hypoglycemic affects?

A

Not approved for use with insulin

Delays gastric emptying

  • Helps with satiety
  • Don’t use in patients with gastroparesis

Yes if given with a SU

57
Q

What are the Amylinomimetics?

A

Pramlintide acetate (Symlin)

58
Q 
Pramlintide acetate (Symlin)
is used for what type of DM?

Describe what it is?

When does it become a high risk for hypoglycemia?

WHat do we use it with?

A

Used for Type 1 and Type 2

Synthetic analog of human amylin cosecreted with insulin by pancreatic beta cells

High risk for hypoglycemia when given with insulin

Add on therapy to insulin or SU or combo of both when failure to achieve A1C goals

59
Q 
Pramlintide acetate (Symlin) MOA?
3
A

Reduces postprandial glucose increases via the following mechanisms:

1) prolongation of gastric emptying time
2) reduction of postprandial glucagon secretion
3) reduction of caloric intake through centrally-mediated appetite suppression

60
Q

Side effects of Prmlintide?

2

A
  1. Nausea/vomiting

2. Hypoglycemia unless insulin dose is simultaneously reduced

61
Q

Contraindications for Prmlintide?

7

A
  1. Gastroparesis
  2. Hypoglycemia unawareness
  3. Poor compliance
  4. Concomitant therapy with drugs that stimulate gastric motility
  5. A1C > 9
  6. Do not use with alpha-glucosidase inhibitors
  7. A fair number of drug interactions that result in hypoglycemia
62
Q

Name the Class, A1C lowering %, Major side effects, and Major contraindications of the following drugs:

  1. Metformin
  2. Glyburide, glipizide, glimepiride
  3. Rosiglitazone, pioglitazone
  4. Acarbose, miglitol
  5. Sitagliptin, saxagliptin
  6. Exenitide, liraglutide, etc.
  7. Canagliflozin, empagliflozin, etc
A
  1. Biguanide
    1.5%
    GI
    Renal insufficiency
    $20
2.  Sulfonylureas
1-2%
--hypoglycemia
C: Sulfa allergy, (elderly)
less than $20
  1. TZDs
    0.5-1.4%
    —Wt gain, CHF, bone loss, fluid retention, hepatotoxicity, CV risks
    C: Liver failure, CHF
    less than $20
  2. Alpha-glucosidase inhibitors
    0.5-0.8%
    –Flatulence, diarrhea
    C: GI motility disorders, diseases of the bowel
  3. DPP-4 inhibitors
    0.7%
    –HA, Pretty well tolerated
    C: Caution renal dz and pancreatitis
    $300
6.  GLP-1
1-1.5%
--GI (nausea)
C: Gastroparesis, severe renal dz
$400-450
  1. SLGT-2
    1%
    –Yeast infection, UTI
    C: GFR
63
Q

Glycemic targets
are what? 3

Who would we want to have tighter targets on?

Lower targets?

A
  1. HbA1c less than 7%
  2. Pre-prandial PG less than 130
  3. Post prandial PG less than 180

Tighter targets (6.0 - 6.5%) - younger, healthier

Looser targets (7.5 - 8.0%+) - older, comorbidities, 	hypoglycemia prone, etc.
Avoidance of hypoglycemia
64
Q

If the pts HbA1C is greater than 9 will a single therapy work?

A

no, you ll need duel therapy from the start

65
Q

For each new class of noninsulin agent added to initial therapy expect A1C lowering of what?

A

0.9-1.1%

66
Q

If there A1C is in the teens then you need to start with what?
4

A
  1. metformin,
  2. basal insulin,
  3. mealtime insulin or a
  4. GLP-1-RA
67
Q

If fasting BG is 180-200 or A1C>9% they likely have no what?

A

beta cell function and need insulin to start

Endocrinology (23 decks)

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