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Pharmacology III > Diabetes Type 1 > Flashcards

Diabetes Type 1 Flashcards

1
Q

When blood glucose is low what is released and from where?

A

Glucagon is released by alpha cells of the pancreas-> liver releases glucose into the blood

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2
Q

When blood glucose is high what is released and from where?

A

Insulin is released by beta cells of the pancreas-> fat cells take in glucose from blood

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3
Q

What is a metabolic disorder in which carbohydrate metabolism is reduced while that of proteins and lipids is increased?

A

Diabetes mellitus

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4
Q

What are the types of DM?

A

Type 1 Insulin-dependent Diabetes (IDDM)
Type 2 Non-Insulin-Dependent Diabetes (NIDDM)
Type 3 Maturity-onset Diabetes of Young (MODY)
Type 4 Gestational Diabetes

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5
Q

What are the characteristics of type 1 DM?

A
  • Usually onset <30y/o
  • Often thin/underweight
  • Polydipsia, polyuria, polyphagia
  • Ketosis is present
  • Endogenous insulin is absent
  • Insulin therapy is required
  • Oral hypoglycemia are usually ineffective
  • Diet changes mandatory w/insulin
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6
Q

What are the characteristics of type 2 DM?

A
  • Usually onset >40y/o
  • Often obese
  • Often asymptomatic
  • Ketosis is usually absent
  • Endogenous insulin is variable
  • Insulin therapy is only required sometimes
  • Oral hypoglycemics are often effective
  • Diet changes are mandatory w/ or w/out drugs.
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7
Q

What is gestation diabetes due to?

A

Due to rises in human placental lactogen & other hormones that contribute to insulin resistance

Results in Congenital abnormalities of fetus

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8
Q

What is Maturity-onset Diabetes of Young (MODY) due to?

A

Dysregulation of glucose sensing or insulin secretion
Autosomal dominant mutation
Occurs before age 25; no obesity; insulin resistance and hypertriacylglycerolemia absent

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9
Q

How is diabetes diagnosed?

A

Fasting plasma glucose (FPG) ≥ 126mg/dl
OR
Symptoms of diabetes + casual plasma glucose ≥ 200 mg/dl (Most Common for Type 1)
OR
Oral glucose tolerance test (OGTT): 2-h postload glucose ≥ 200 mg/dl

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10
Q

What causes type 1 diabetes?

A

Absolute insulin deficiency
Autoimmune destruction of the B-cells of the pancreas (markers include Islet cell antibodies
Autoantibodies to insulin
Autoantibodies to glutamic acid decarboxylase (GAD65)
Autoantibodies to tyrosine phosphatases IA-2 and IA-2β)

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11
Q

What are the risk factors for Type 1 DM?

A

Strong genetic component- associated with HLA and linked to DQA and DQB genes, identical twins, HLA identical siblings, HLA non-identical siblings
Environmental factors- viruses

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12
Q

When are most cases of Type 1 DM diagnosed?

A

Before the age of 30
Incidence is decreased after age 20
Incidence is higher in Whites and pts are more prone to other autoimmune disorders.

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13
Q

What are the four main features of the progression of Type 1 DM?

A
  1. Pre-clinical period with the presence of immune markers
  2. Hyperglycemia after 80-90% of B-cells are destroyed
  3. Honeymoon phase-transient remission
  4. Established disease
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14
Q

What are the clinical presentation sx of HYPERGLYCEMIA?

A 
Polyuria
Polydipsia
Polyphagia
Weight loss
Fatigue
Infections
Blurred vision
Poor healing
Growth failure in children
Nausea and vomiting
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15
Q

What does treatment consist for type 1 DM?

A

Providing exogenous insulin to replace endogenous loss
Insulin
Pramlintide

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16
Q

What are the effects of insulin in the liver in high-insulin state?

A

Glucose uptake
Glycogen synthesis
Lipogensis

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17
Q

What are the effects of insulin in the muscle in high-insulin state?

A

Glucose uptake
Glucose oxidation
Glycogen synthesis
Protein synthesis

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18
Q

What are the effects of insulin in adipose tissue in high-insulin state?

A

Glucose uptake Lipid synthesis

Triglyceride (TG) uptake

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19
Q

What are the effects of insulin in the liver in low-insulin state

A

Glucose production
Glycogenolysis
Ketogenesis

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20
Q

What are the effects of insulin in the muscle in low-insulin state?

A

Fatty acid, ketone oxidation
Glycogenolysis
Proteolysis and amino acid release
NO glucose uptake

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21
Q

What are the effects of insulin in the adipose tissue in low-insulin state?

A

Lipolysis and fatty acid release

NO glucose or TG uptake

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22
Q

What are the rapid acting types of insulin?

A

Humalog® (lispro)
Novolog ® (aspart)
Apidra ® (glulisine)

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23
Q

What are the short acting-regular (R) types of insulin ?

A

Novolin® R

Humulin® R

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24
Q

What are the intermediate acting-NPH (N) types of insulin?

A

Novolin® N

Humulin ® N

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25
Q

What are the long acting- basal insulin?

A

Levemir® (detemir)

Lantus® (glargine

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26
Q

Detemir (Levemir)

A

Long acting/basal insulin
An attached fatty acid side chain binds to interstitial albumin at the SC site
Binds to albumin again in the capillary
Must dissociate from albumin to bind to insulin receptors

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27
Q

Glargine (Lantus)

A

Long acting/basal insulin
Soluble at a pH of 4
Forms microprecipitates when injected into the body
Slowly dissolves into monomers which are absorbed

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28
Q

Insulin detemir (Levemir)

A 
Long acting/basal insulin
Onset: 2 hrs
Peak: 6 to 9 hrs (blunted)
Duration: ~24 hours (0.4 units/kg)
~14 hours when dosed 0.2 units/kg
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29
Q

Insulin glargine (Lantus)

A

Long acting/basal insulin
Onset: 4 to 5 hrs
Peak: none or blunted
Duration: 22+ hrs

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30
Q

Neutral Protamine Hagedorn (NPH)
Novolin® N
Humulin® N

A

Intermediate-acting insulin NPH
Onset: 1 to 4 hrs
Peak: 6 to 10 hrs
Duration 12-18 hours

NPH is a suspension
Must be rolled or inverted 10 times before use to resuspend

Can be used as a basal insulin when dosed multiple times a day

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31
Q

Novolin® R

Humulin® R

A 
Short acting insulin- regular
Can be mixed in same syringe with NPH
Onset: ½ to 1 hour
Peak: 2 to 5 hrs
Duration: 4 to 6 hrs

Inject ~30 minutes before eating
Can be inconvenient- requires more meal planning
Delayed onset useful in patients with gastroparesis

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32
Q 
Insulin Lispro (Humalog®)
Insulin Aspart (Novolog ®)
A

Rapid-acting insulin
Onset 5-15 minutes
Peak: ½ to 1 ½ hrs
Duration 3.5- 5 hours

More closely mimics the body’s response to glucose absorption
Should be injected immediately before eating
Can be mixed with NPH, but must inject within 5 minutes (doesn’t have as long of stability so must be stored)

33
Q

What are the pre-mixed types of insulin: basal/bolus?

A

NPH + Regular -70/30 (NPH/R) :Novolin® 70/30
Humulin® 70/30

NPH-like insulin + Rapid-acting
Aspart Protamine/Aspart
Novolog Mix® 70/30

Neutral Protamine lispro/lispro
Humalog Mix® 75/25
Humalog Mix 50/50

34
Q

Pre-mixed insulin:Basal/bolus
Novolog Mix® 70/30
Humalog Mix® 75/25

A

Cloudy appearance: mix (DONT ROLL) before administering

Onset is 5 to 15 minutes (give immediately before meal)

35
Q

Pre-mixed insulin:Basal/bolus
70/30 (NPH/R)
Novolin® 70/30
Humulin® 70/30

A

Cloudy appearance: mix (DONT ROLL) before administering

Onset- 1/2 to 1 hour (give 30 minutes before meals)

36
Q

What are the insulin adverse effects?

A 
Hypoglycemia: blood glucose < 70 mg/dL
Result of:
Excess of insulin
Decrease or delay in meals
Increase in exercise
Illness
37
Q

What are the signs and sx of insulin adverse effects?

A

Tremors, palpitations, sweating
Excessive hunger
Headache, mood changes, irritability
Unconsciousness, seizures

38
Q

What is the treatment for insulin adverse effects?

A

15 g of glucose….wait 15 min
If blood glucose still <70 mg/dL take another 15 g
Repeat until blood glucose is in normal range
Eat a meal or snack to prevent recurrence

39
Q

What are the glucose products that are sources of carbohydrates?

A

Tablets: 5g/tab
Gel: 15 g/tube

40
Q

What are foods that are sources of carbohydrates?

A 
Food ( amt = 15g)
½ cup juice or regular soda
3 graham crackers
6 saltines
1 Tbsp syrup or honey
1 cup skim milk
2 Tbsp raisins
41
Q

Insulin- Adverse effects

A 
Hypoglycemic unawareness
Weight gain
Lipohypertrophy
Hypokalemia
Allergic reaction at injection site-rare
Insulin antibodies- rare
42
Q

What is hypoglycemic unawareness?

A

Secretion of glucagon and epinephrine are blunted
Reduced symptoms of hypoglycemia
Symptoms still might occur but at lower blood glucose levels
Less time to react and treat

43
Q

How do you treat hypoglycemic unawareness?

A

If patient is unconscious use a glucagon kit to treat hypoglycemia
1 mg IM
Patient should respond within 15 minutes
Can be repeated if no response

44
Q

Insulin- administration

A

-Route of administration affects rate of absorption
IV > IM > SC
-Rates of absorption vary from site to site
Abdomen (Fastest) > arm > thigh > buttocks (Slowest)
-Patient should be consistent in the area they are injecting but still rotate the point of injection within injecting, that site
-Blood flow to the area enhances absorption
Rubbing injection area, skin temperature, exercise

45
Q

Where does insulin need to be stored?

A

Most insulins can be stored at room temperature 15-30°C (59-86°F) up to 28 days

46
Q

What are the exceptions to insulin storage norms?

A

The Mix pens

47
Q

What are insulin pumps?

A

Continuous Subcutaneous Insulin Infusion
Delivers microliter amounts of insulin continuously as a basal insulin
Delivers insulin via flexible tubing connected to a catheter inserted subcutaneously

Activate the pump before a meal to deliver a bolus
Battery operated device
Insulin reservoir-varying sizes

48
Q

Pramlintide (Symlin™)- MOA

A

-Synthetic analog of human amylin
-Amylin is co-secreted with insulin from the pancreas in response to a meal
-3 primary mechanisms of amylin
Suppresses postprandial glucagon secretion
Regulates the rate of gastric emptying
Reduces food intake
-Amylin is deficient in both type 1 and type 2 diabetes

49
Q

Pramlintide (Symlin™)- indications

A

FDA approved for Type 1 or 2 diabetes in patients on optimal insulin therapy who are still not at goal

Efficacy: A1C ~0.1-0.4% in type 1 diabetes

50
Q

Pramlintide (Symlin™)- dosing

A

Type 1 dosing: 15 mcg SC before meals
Meals must be >250 kcals or >30 g carbohydrates
Titrate at 15 mcg increments to a max of 60 mcg before meals
SymlinPen™ 60: for doses of 15, 30, 45, or 60 mcg
SymlinPen™ 120: for doses of 60 or 120 mcg

Administered in conjunction with mealtime insulin

51
Q

What should you reduce when starting pramlintide?

A

When starting pramlintide reduce pre-prandial insulin by 50%

52
Q

Pramlintide (Symlin™)- contraindications/precautions

A

Gastroparesis
Hypoglycemic unawareness
Recurrent episodes of hypoglycemia in the last 6 months
A1C > 9%
Poor adherence to insulin or self-monitoring

53
Q

Pramlintide (Symlin™)- Adverse effects

A

HYPOGLYCEMIA- BLACK BOX WARNING (usually occurs within 3hrs of injection, reason you reduce preprandial insulin by 50% at initiation)

Nausea
Titrate dose slowly

54
Q

Pramlintide (Symlin™)- drug interactions

A

Delayed gastric emptying

Administer oral meds 1 hr pre or 2 hr post pramlintide

55
Q

What are the ADA guidelines for glycemic control goals for type I and II?

A

A1C < 7.0%
Fasting glucose 70-130 mg/dl
Peak postprandial glucose <180 mg/dl
1-2 hours after the start of the meal

56
Q

What are the AACE guidelines for glycemic control goals for type I and II?

A

A1C < 6.5%
Fasting glucose < 110 mg/dl
2-h postprandial glucose <140 mg/dl

57
Q

What is the recommended therapy for Type I DM?

A
  1. Use of multiple dose insulin injections
    3-4 injections/day of basal and prandial insulin
  2. Matching prandial insulin to:
    Carbohydrate intake
    Premeal BG
    And anticipated activity
  3. Use of insulin analogs as prandial insulin
58
Q

What is the standard of care in Type I diabetes?

A

Long-Acting Basal with Rapid-Acting Bolus

Minimum of 4 injections
Basal administered once/day typically at bedtime
Rapid acting bolus given just before meals

59
Q

What are other regimens that can be used for Type I DM but are more commonly used for Type II?

A

-NPH Basal with Rapid Acting Bolus
Limited use in type 1
Basal doesn’t last 24 hours
Greater risk for hypoglycemia: peak from NPH
Less expensive regimen
-Mixed insulin before breakfast and dinner
Very difficult to adjust the dose if it is pre-mixed
-Pre-breakfast NPH + regular, pre-dinner regular, and bedtime NPH
-Detemir/glargine once or twice daily with regular insulin before meals

60
Q

Basal insulin- Dosing

A

Initial insulin dosing for type I is weight based
~0.4-1 units/kg/day
~50% of Insulin total daily dose (TDD) is basal insulin
Remaining ~50% is given as prandial insulin
Max of 50 units can be absorbed/injection site

61
Q

Prandial (Bolus) Insulin- Dosing

A
  • When using rapid-acting insulin- inject immediately before the meal
  • When using regular insulin- inject 30-45 minutes before the meal

2 parts to prandial insulin dosing:
1. Insulin to carbohydrate ratio (I:C)
Grams of carbohydrate 1 unit of insulin will cover
2. Correction factor (CF)
Number of mg/dL the blood glucose will drop after injecting 1 unit of rapid-acting or regular insulin

62
Q

What is the insulin to carbohydrate ratio?

A

Typical starting I:C is 1:15
1 unit of insulin “covers” 15 grams of carbs
OR…use a formula to determine the I:C
500 / TDD = # of carbs covered by 1 unit of insulin
(TDD = Total daily dose of insulin)

Example: TDD= 25 units
500/25 = 20 (I:C = 1:20)

63
Q

How many grams are in one serving of carbohydrates?

A

15 grams

64
Q

What is basic carb counting?

A

Limit patient to a specific # of carb servings/meal
e.g. can have 4 carb servings or 60 grams of carbs/meal
Patient has a set insulin dose

65
Q

What is advanced carb counting?

A

Patient counts the grams of carbohydrates in the meal and injects the appropriate amount of insulin according to the I:C
Remind patients to look at serving size and Total Carbohydrates

66
Q

What is the correction factor?

A

Number of mg/dL the blood glucose will drop after injecting 1 unit of rapid-acting or regular insulin
Use the CF when the patients blood glucose is elevated before the meal
This insulin will be added to the amount required to cover the carbs that will be consumed
A typical starting CF dose is 1:50 mg/dL
1 unit of insulin for every 50 mg/dL above 100
Correct to 100 mg/dL because it is the mid-point target blood glucose (between 70 and 130 mg/dL)

67
Q

When should you make adjustments to insulin?

A

When patterns are out of range

68
Q

Which insulin should be adjusted in fasting hyperglycemia?

A

Increase bedtime basal insulin dose 1-2 units every 3 days until fasting blood sugar <130mg/dL
Other causes of fasting hyperglycemia
Dawn phenomenon: increased insulin requirement late in the sleep cycle (nocturnal hyperglycemia)
Somogyi phenomenon: nocturnal hypoglycemia followed by rebound hyperglycemia

69
Q

What is the somogyi effect?

A

-During hypoglycemia counterregulatory hormones are released
Glucagon, epinephrine, growth hormone, cortisol
Stimulates hepatic glucose production- can lead to rebound hyperglycemia
-Measure blood glucose levels between 2 and 4:00 AM and then again at 7:00 am
If they are 180-200 mg/dL rebound hyperglycemia may have occurred
-More common when intermediate insulins are used with dinner
-Less risk of nocturnal hypoglycemia with long-acting basal insulins

70
Q

What is the dawn phenomenon?

A

Increased insulin requirement in the early morning
~1-3:00 am due to a surge of growth-hormone release
If the patient’s insulin levels are starting to drop at this time, it will result in morning fasting hyperglycemia
NPH is effective due to its peak

71
Q

How do you know which insulin to adjust for post-prandial hyperglycemia (>180mg/dL)?

A

1-2 hours after eating
Not enough insulin was given with the meal
Increase the pre-meal insulin dose
Trial and error to determine if the I:C ratio or the CF need increased

72
Q

How do you adjust the insulin:carb ration?

A

Adjust the I:C by 2-5 grams of carbs when the postprandial blood glucose is consistently > 180 mg/dL
If I:C is 1:15 and the 2-h post-prandial blood glucose levels are 210…
Increase the I:C to ~1:12
Verify that the patient is correctly counting the carbs!
If I:C is 1:15 and the patient is frequently hypoglycemic 2 hours after eating…
Decrease the I:C to ~1:20

73
Q

How is insulin managed during exercise?

A

Exercise-induced hypoglycemia occurs as a result of ↑ glucose uptake and utilization by the muscle

74
Q

How do you avoid hypoglycemia during exercise?

A
  • Planned exercise: decrease pre-prandial insulin dose before the exercise
  • Unplanned exercise: consume an additional 15-30 g of carbs for each 30 min of exercise
  • Might need to decrease pre-prandial insulin dose for the meal after exercising
75
Q

How is insulin managed during illness?

A

-Insulin requirements increase during illness
-Risk for diabetic ketoacidosis (DKA)
-Patient needs to continue their usual insulin doses
If able to eat might need an additional unit/15 g of carbs
-Check blood glucose and urine ketones
-Always test urine ketones if blood glucose is consistently over 240 mg/dL
-Persistent large ketones is an early sign of DKA

76
Q

What are the complications of DM I?

A

Hypoglycemia- BG <50mg/dL
Ketoacidosis-Without insulin body must obtain energy via lipolysis leading to ketone bodies
DKA is a reversible but potentially life threatening complication
Often precipitated by illness, incorrect insulin dosing (or oral DM meds)

77
Q

What are the signs and symptoms of diabetic ketoacidosis?

A 
Develop rapidly
Fruity or acetone breath
N+V
Dehydration- typically 6L or more
Polyuria
Polydipsia
Deep, rapid breathing
Lethargy, HA, weakness
78
Q

What is the diagnostic criteria for diabetic ketoacidosis?

A

Hyperglycemia (> 250mg/dL)
Ketosis (anion gap > 10)
Acidosis (arterial pH < 7.25)

79
Q

What is the treatment of ketoacidosis?

A

-Reverse underlying metabolic abnormalities
Rehydrate patient
-Replacement with NS at 1L/hr (a lot of fluid to replace)
-Normalize serum glucose (use a regular insulin)
Regular insulin at 0.1-0.2 unit/kg/hr by CI (continuous infusion)

Pharmacology III (19 decks)

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