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Drug Action II > Block 3: Insulins > Flashcards

Block 3: Insulins Flashcards

1
Q

What are the presentations of T1DM?

A
  1. C-peptide usually low or absent2
  2. Polyuria
  3. Polydipsia
  4. Polyphagia
  5. Ketoacidosis
  6. Weight loss
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2
Q

Describe the pharmacology of insulin?

A
  1. Anabolic hormone
  2. Protein, carbohydrate and fat metabolism
  3. Lowers blood glucose levels by stimulating peripheral glucose uptake, inhibits lipolysis and proteolysis, enhances protein synthesis
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3
Q

Commercial insulins are categorized by?

A
  1. DOA
  2. Onset
  3. Concentration
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4
Q

PK properties of insulin?

A

Absorption is dependent on:
* Concentration of insulin
* Additives/formulations
* Injection site: Abdomen -> Arms -> Thighs -> Buttocks
* Blood flow

Insulin is metabolized mostly in liver and kidney

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5
Q

ADRs of insulin?

A
  1. Hypoglycemia
  2. Weight gain
  3. Hypokalemia
  4. Lipodystrophy
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6
Q

What is the cause of lipodystrophy?

A
  1. Not rotating injection site
  2. Reusing needles
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7
Q

Types of lipodystrophy?

A

Lipohypertrophy:
* Increased mass at injection site
* Caused by repeat injections of insulin at the same site

Lipoatrophy:
* Decreased mass at injection site
* Caused by insulin antibodies

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8
Q

DDIs of insulin?

A

Drugs that affect glucose control:
1. Steroids
2. Diuretics
3. Beta blockers
4. Alcohol
5. Thyroid

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9
Q

Ultra rapid acting insulins?

A

Insulin Lispro-aabc (Lyumjev, Lilly)
Insulin Aspart (Fiasp, Novo Nordisk)

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10
Q

Rapid acting insulin analogies?

Place in therapy, Onset, DOA

A

Insulin Lispro (Humalog, Lilly)
Insulin Aspart (NovoLog, Novo Nordisk)
Insulin Glulisine (Apidra, Sanofi Aventis)

P-in-T: Used to lower post-prandial glucose levels
Onset: Faster, Better mimics physiological postprandial insulin secretion
DOA: Shorter

Still requires the need for basal insulin replacement

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11
Q

Short acting insulins

Brands, Place in therapy, Admin

A

Regular (Humulin R, U100 and U500 (Lilly) Novolin R (Novo Nordisk))

P-in-T: lower post-prandial glucose levels generally as a “bolus” insulin dose
Admin: 30 min prior to meals,

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12
Q

Intermediate acting insulins?

A

Isophane NPH (Humulin N, Novolin N)

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13
Q

Long acting insulins?

A

Insulin Glargine (Lantus, Toujeo, Sanofi Aventis; Basaglar, Lilly)
Insulin Detemir (Levemir, Novo Nordisk)
Insulin Degludec (Tresiba, Novo Nordisk)

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14
Q

Pharmacokinetic Profiles of Insulins

A
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15
Q

When is U-500 used?

A

Highly insulin resistant patients, however, has an altered PK profile

U-100 insulin is 2.5 - 5 hrs
U-500 insulin at about 4 - 8 hrs

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16
Q

Limitations of human regular insulin?

A

Relatively slow onset of action from SQ injection:
* Mismatch with postprandial hyperglycemic peak

Longer DOA:
* Potential for late postprandial hypoglycemia

Insulin R fails to re-create the physiological insulin profile

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17
Q

What is the physiological insulin profile?

A
  1. Basal component
  2. Meal-related peaks
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18
Q

How are rapid-acting analogues absorped into the body?

A

Amino Acid changes decrease the amount of self-association and produces a more rapid dissolution of insulin dimers and hexamers

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19
Q

How does rapid insulin analogues compare to physiological insulin?

A

Better Mimicry: Rapid-acting insulin analogues together with a basal insulin component provide physiological insulin replacement

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20
Q

What is Fiasp?

A

Insulin aspart + Vitamin B3 (Niacinamide) to increase the speed of absorption, and L-arginine to stabilize the formulation

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21
Q

What is Lymjez?

A

Insulin lispro with the following excipients:
* Treprostinil: a prostacyclin analog which causes local vasodilation and a more rapid absorbtion
* Citrate: speeds insulin absorption by enhancing vascular permeability

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22
Q

What are the ultra-rapid acting analogues?

A
  1. Fiasp
  2. Lyumjev
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23
Q

What are the advantages of Ultra rapid?

A

1.“Faster onset of action” can help reduce post-prandial glucose spikes
2.Can be taken just prior or after initiation of meals without causing a glucose spike
3.use in insulin infusion pumps

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24
Q

Disadvantages of ultra-rapid?

A

If there is any delay in mealtime it may cause hypoglycemia

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25
Q

Inhaled ultra rapid-acting mealtime insulin therapy for Type 1 and Type 2 diabetes

CI

A

Afreezza
CI: asthma, COPD

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26
Q

What are the types of basal insulins?

A

NPH

True basal:
1. Glargine (Lantus, Basaglar, Toujeo): peakless, ~24 hr
2. Detemir (Levemir): small peak, ≤ 24 hr
3. Degludec (Tresiba): “peakless, ~36 hr

27
Q

What are the advantages and disadvantages of basal insulins?

A

Pros: nearly peakless and given once daily
Cons: cost

28
Q

How should basal insulins be administered?

A

QD usually at nihgt

Lantus, Degludec and Levemir should not be mixed with other insulin products

29
Q

Describe the structure of insulin glargine?

A
  • Substitution of glycine at position A21
  • Addition of 2 arginines at position B30
30
Q

Describe the sustained release of insulin glargine?

A
  1. Injection of an acidic solution (pH 4.0)
  2. Microprecipitation of insulin glargine in the subcutaneous tissue (where pH = 7.4)
  3. Slow dissolution of free insulin glargine hexamers from microprecipitates (stabilized aggregates)
  4. Protracted duration of action
31
Q

Compare the difference between glargine and NPH?

A

Significantly lower incidence of nocturnal hypoglycemia with insulin glargine compared with NPH

32
Q

Describe the structure of levemir?

A
  1. Removal of B30 threonine
  2. Acylation with myristic acid to B29 lysine
  3. Remains a solution after injection
  4. Neutral pH
  5. DOA is up to 24hr
  6. Cmax reached 6-8 h after administration
33
Q

How is Levemir adminsitered?

A

Should not be mixed with other insulin products

FlexPen® is a dial-a-dose insulin pen. Doses can be dialed from 1 to 60 units in increments of 1 unit.

34
Q

Describe the MOA of levemir?

A
  1. At injection, self-associates and bind to albumin
  2. Albumin binds to blood
  3. Drug travels to target tissue
35
Q

Describe the MOA of insulin degludec?

A

Immediately after injection
1. Injected as dihexamers
2. Phenol from the vehicle diffuses off quickly, and insulin degludec assembles or links up via single side-chain contacts or long chain “multi-hexamers”

Slow release following injection:
1. Insulin degludec
Multihexamers are stable in the subcutaneous space
2. Zinc diffuses away slowly, causing individual hexamers to disassemble, releasing monomers
3. Monomers are absorbed from the depot site into the circulation

36
Q

How do you store insulin?

A
  1. Refrigerate unopen insulin
  2. Store currently opened vial at room temperature 59-86ºF
  3. Use vials within 28-30 days
  4. DO NOT FREEZE or expose to extreme conditions.
  5. Cartridges and pens may have shorter storage times for NPH and mixed insulins (typically 7-14 days)
37
Q

What are the regular remixed insulin?

A

NPH/Regular: Humulin 70/30, Novolin 70/30

38
Q

What are the analogue premixed insulins?

A

Insulin aspart protamine / insulin aspart: NovoMix 70/30
Insulin lispro protamine / insulin lispro: Humalog mix 75/25 & 50/50
30% Apart / 70% Degludec: Ryzodeg 70/30

39
Q

How can you mix insulins?

A
  1. NPH and short-acting insulin may be mixed
  2. Rapid-acting insulins can also be mixed with NPH
  3. NO MIXING with ANY form of insulin with LANTUS or DETEMIR
40
Q

How do you prepare insulin for injection?

A
  1. Room temp
  2. Verify label is correct insulin; inspect for contaminates
  3. GENTLY roll insulin suspensions (Don’t shake)
  4. When mixing, always withdraw from the bolus (fast acting or clear) insulin FIRST
  5. Rotate injections sites within a single area BEFORE moving to another site
41
Q

What are the insulin injection sites?

A

Fastest to slowest:
Abdomen&raquo_space; Arms > Thighs > Butt

42
Q

What does the physiological profile of insulin look like?

A

Goal is to produce a physiological profile in diabetic patients

43
Q

What is the basal/bolus insulin concept?

A

For insulin replacement therapy, each insulin component should come from a different insulin with a specific absorption profile (differing times of onset and durations of action), OR by using an insulin pump.

44
Q

What is the therapeutic goal for basal?

A
  1. Suppresses glucose production between meals and overnight
  2. Constitutes approximately 50% of daily insulin needs
  3. Mimics the nature of insulin therapy
45
Q

When do you use Correction (supplemental) insulin?

A

Treats acute elevations in blood glucose generally found during pre-meal testing

46
Q

What is the purpose of using insulin in T1DM?

A

To mimic normal basal-bolus insulin production
* usually accomplished by split dosing or insulin pump

47
Q

What does 2 doses/day look like?

A

Split-mixed doses:
(Intermediate) acts as basal insulin (NPH)
(Short) acts as bolus insulin (Regular)

Doesn’t provide a tight control or mimic physiological insulin release

48
Q

What would the insulin peaks look like with Twice-Daily Premixed 70/30 Insulin?

A

Both insulins combined increase plasma levels

49
Q

What does 3 doses/day look like?

A

Split doses:
(Intermediate) acts as basal insulin (NPH)
(Rapid) acts as bolus insulin (Lispro)

Provides better glycemic control but still with increased risk of hypoglycemia.

50
Q

What does 4 doses/day look like?

A

Rapid-acting (R) with each meal and Long-acting (L) at HS:
1. Basal insulin (Glargine)
2. Bolus insulin (Lispro)

Most closely mimics physiological release of insulin, providing the best control with a reduced risk of hypoglycemia

51
Q

Why do you have 4 injections in 4 doses/day?

A

Glargine can not be mixed with lispro

52
Q

What are sick daya?

A

Patient with T1DM:
May take more to control blood sugar during illness

  • Monitor blood glucose levels and use rapid to correct blood sugar levels
  • Drink gatorade/electrolytes
53
Q

What is the only way to overcome glucose tox?

54
Q

Treatment for fasting glucose tox?

A

add a basal insulin at bedtime

55
Q

Treatment for post-prandial glucose?

A
  1. Add rapid acting analog or mixed analog before largest meal, Increase insulin dose every 3 days if not at goal and have no occurrences of hypoglycemia
  2. Utilize insulin type and amount based on what is needed to achieve glycemic goals
56
Q

What are the barriers to insulin use?

A

“Psychological insulin resistance” and fear of Needles

57
Q

What are the outcomes of T2DM being a progressive disease?

A

Many patients with type-2 diabetes may need insulin to control glucose levels

58
Q

How do you start basal insulin?

A
  1. May continue oral agent(s) at same dosage (may be able to reduce)
  2. Simple: Basal insulin (NPH, Glargine) 10 units qhs & titrate to control
  3. Calculated methods
59
Q

Pre-breakfast (fasting) insulin problems?

A

Dose: Pre-dinner NPH or long acting insulin
Meal: Bedtime snack

60
Q

Pre lunch insulin problems?

A

Dose: Pre-breakfast regular or rapid acting insulin
Meal: Breakfast / midmorning snack

61
Q

Pre dinner insulin problems?

A

Dose: Pre-breakfast NPH or pre-lunch regular or rapid acting insulin
Meal: Lunch / midafternoon snack

62
Q

2-Hr post-prandial insulin problems?

A

Dose: Pre-meal rapid acting insulin
Meal: Preceding meal or snack

63
Q

Bedtime insulin problems?

A

Dose: Pre-dinner regular or rapid acting insulin
Meal: Dinner

64
Q

3AM Insulin problems?

A

Dose: Evening NPH or long acting insulin, dinner regular insulin
Meal: Dinner or bedtime snack

Drug Action II (28 decks)

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