L 34.2 Flashcards

1
Q

What is the goal of all insulin treatment?

A

To mimic the healthy pancreas’ way of secreting insulin to the bloodstream

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2
Q

Insulin consists of … amino acids that form … polypeptide chains, and these … chains are linked by … bridges

A

Insulin consists of 51 amino acids that form 2 polypeptide chains, and these 2 chains are linked by disulfide bridges

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3
Q

What are 5 examples of therapeutic insulins?

A

Beef, pork, human, human analogues, human recombinants

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4
Q

What is the Quick overview of insulin production by recombinant DNA tech?

A

Gene is cloned into the plasmid and then transfected

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5
Q

What is the standard route for the administration of insulin?

A

Subcutaneous as the diffusional barrier provides a delayed release and sustained release as the insulin has to partition or diffuse across the tissue to get to the vascular system.

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6
Q

Why not the oral, IV or IM route?

A

Oral: peptide will get broken down in stomach
IV: Good spike but cleared quickly from blood - not sustained
IM: close to blood vessels so are getting responses between IV and SC. Not as long lasting as SC
The best route of administration of insulin is SC

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7
Q

What are the 3 examples of insulin delivery devices?

A

Needle and Syringe, injectable pen, insulin pump (continuous delivery)

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8
Q

How does insulin form a stable structure?

A

Insulin forms a hexamer structure around Zn2+

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9
Q

When insulin enters into the human SC tissue, it ………?

A

When insulin enters into the tissue, it dissociates into dimers and then into monomers.

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10
Q

Can insulin monomers or dimers diffuse into the capillaries?

Can monomers reassociate? Can dimers?

A

Both insulin and monomers can dissolve into the capillary, but dimers have limited diffusion compared to monomers which have rapid diffusion.
Dissociation/reassociation: Hexamer Dimer Monomer

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11
Q

What are the Limitations of regular human insulin?

A
  • Injections required 30-45 mins before meals = patient inconvenience (coordination required), safety concerns (hypo/hyper) if meal not eaten when scheduled.
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12
Q

What are examples of rapid acting insulin?

A
Insulin lispro (Humalog)
Insulin aspart (Novolog)
Insulin glulisine (Apidra)
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13
Q

What is an example of short acting insulin?

A

Regular insulin

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14
Q

What is an example of intermediate acting insulin?

A

Neutral Protamine Hagedorn Insulin (NPH) aka isophane insulin.

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15
Q

What is an example of long acting insulin?

A

Insulin glargine (Lantus)

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16
Q

How are insulins categorized?

A

First by length of action

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17
Q

Factors influencing the insulin effect x4. How do they affect it?

A

Temperature - increased heat (e.g shower, sauna) = inc BF = faster absorption absorption
Injection site - Rate = Abdominal > buttocks > thigh because … has higher vasculature
Massaging injection site - increased BF = increased absorption
SC fat thickness - thicker fat layer = slower absorption

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18
Q

Rapid fast acting insulin profile

A
  • Onset 15 mins
  • Peak 1 hour
  • Lasts 2-4 hours
  • Taken directly prior to a meal with long acting insulin
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19
Q

Short-regular acting insulin profile

A
  • Onset 0.5-1 hour
  • Peak 2-3h
  • Lasts 6-8h
  • Given before a meal with long acting insulin
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20
Q

Intermediate acting insulin profile

A
  • Onset 2-4h
  • Peak 4-8h
  • Lasts 12-18h
  • Taken 2x a day + short/rapid acting insulin
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21
Q

Long acting insulin profile

A
  • Onset several hours
  • No ‘peak’ as such, but steady effect
  • Lasts 24h
  • Often given in combo with rapid/short acting insulin.
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22
Q

What are the brand names for these generics:

A
Insulin Aspart
Insulin Glulisine
Insulin Lispro
Insulin aspart - novorapid
Insulin glulisine - apidra
Insulin lispro - humalog
23
Q

Onset of most rapid acting insulins
Duration of action
When to take rapid acting insulins

A

15 mins (10-20 mins)
Up to 5 hours
Take immediately before a meal or w/in 20 mins of starting a meal

24
Q

Why does rapid lispro (humalog) work quicker than soluble human insulin?

A

What changes were made?
It blocks the reformation of insulin dimer and hexamers.
Recombinant DNA tech reverses the final lysine and proline.

25
Q

Rapid insulin lispro is only absorbed as…?

A

Rapid insulin lispro is only absorbed as monomers

Why does Insulin apart (rapid novolog) work quicker than human insulin?

26
Q

What changes were made?

A

It works quicker by having a reduced tendency to form hexamers.
Changed by exchanging proline for aspartic acid (changing 1 amino acid)

27
Q

Rapid insulin MoA

What does this make the absorption curve look like?

A

Prevent self association of the monomers into dimers and dimers into hexamer forms.
Faster onset, faster peak, shorter duration

28
Q

Components of insulin aspart?

A

Zinc ion, buffer, preservatives (phenol), isotonicity agents

29
Q

Short acting insulin reaches the bloodstream … after injection, peaks …. after injection and is effective for …. after injection?

A

Short acting insulin reaches the bloodstream 0.5-1 hour after injection, peaks 2-3h after injection and is effective for 6-8h after injection

30
Q

What is the generic and 2 brand names for short acting insulin?

A

Short acting insulin = human neutral insulin.
2 brands = actrapid and humulin R
Onset of action for short acting insulin

31
Q

What is the Duration of action of short acting insulin?

A

When to take short acting insulin
Onset: 30 mins
Duration: 6-8h
When to take: 30 mins before a meal

32
Q

MoA of short acting insulin?

A

Same as regular human insulin: hexamer dimer monomer —> blood vessel.
Dimer can also be absorbed.

33
Q

Intermediate acting insulin reaches the bloodstream… after injection, peaks …. after injection and is effective for … after injection?

A

Intermediate acting insulin reaches the bloodstream 2-4h after injection, peaks 4-8 hours after injection and is effective for 12-18h after injection

34
Q

What is the generic and 2x brand names for intermediate acting insulin?

A

Intermediate acting insulin = Insulin isophane human

Brand names: Humulin NPH and Protaphane

35
Q

What is the onset of action for intermediate acting insulin?

Is NPH or protaphane longer?

A

60 - 90 mins

Protaphane = 90 mins. NPH = 60 mins

36
Q

What is the duration of action for intermediate acting insulin?
When do you take it?

A

Duration: 16-24 hours

Take it at the same time every day

37
Q

What does NPH insulin stand for?

A

Neutral protamine Hagedorn.
Neutral = pH 7
Protamine (suspension)
H = Hans Hagedorn (researcher)

38
Q

What changes to NPH have been made?
What does the solution look like?
What do you need to do before drawing from the vial?

A

NPH is made by mixing regular insulin and fish protein (protamine) reduces absorption and increases duration of action.
Hazy solution (suspension)
Need to roll a vial between pals to thoroughly mix before drawing from it.

39
Q

Delayed release due to insulin being negatively charged at 7.4 so the insulin hexamers form a protamine-insulin complex. These particles make up the suspension and have a slow dissociation back into hexamers then into dimers and monomers.

A

What is the mechanism of action for intermediate acting insulin?

40
Q

Long acting insulin starts working … after injection and works for approximately …

A

Long acting insulin starts working 2-4 hours after injection and works for approximately 24 hours.

41
Q

What are some generic names for long acting insulin and their matching brand name?

A

Insulin degludec - Tresibla
Insulin detemir -levemir
Insulin glargine - lantus

42
Q

When is steady state reached for long acting insulin?

A

Duration of action

43
Q

When to take?

A

Steady state reached after 2-4 hours.
Duration: up to 24h
Take same time daily (tresiba = od, levemir and lantus bd)

44
Q

Is lantus a human insulin analogue?

What is MoA?

A

Yes, lantus is a human insulin analogue.

MoA: Lantus uses pH to form micro-precipitates under the skin, so the micro-crystals slowly release insulin for ~24h

45
Q

How does insulin glargine differ from human insulin?

A

Human insulin has replaced asparagine with glycine. This change shifts the isoelectric point and makes the insulin more soluble at an acidic pH, and less soluble @ 7.4.

46
Q

What does the isoelectric shift also allow for?

A

Allows for the subcutaneous injection of a clear solution.

47
Q

What impact does change the isoelectric shift have on the injection profile?

A

Injecting the acidic insulin solution under the skin (pH 7.4) means there will be a precipitation of crystals. This causes a slow dissociation from crystals into hexamers, dimers, and monomers, therefore, achieving a long-acting insulin profile.

48
Q

What is an insulin mixture called?

A

Biphasic insulins

49
Q

What are the generic names (and corresponding brand names) for biphasic insulins?

A

Biphasic insulin lispro (Humalog Mix25, Humalog Mix50)
Biphasic isophane insulin (Humulin 30/70, Mixtard, Penmix)
Biphasic insulin apart (NovoMix30)

50
Q

What is the general onset time for insulin mixtures?

A

10-30 minutes

Biphasic isophane insulin = 30 minutes

51
Q

What is the duration of action for biphasic insulins?

When do you take biphasic insulin lispro/biphasic insulin apart and biphasic isophane insulin?

A

Up to 24 hours
Biphasic insulin lispro and biphasic insulin apart: Same time each day, immediately before a meal.
Biphasic isophane insulin: 30 mins before a meal

52
Q

Premix insulin analogs mimic…..

A

Premix insulin analogs mimic physiological insulin secretion

53
Q

Mixture-insulins can vary in the … of the …

A

Mixture-insulins can vary in the fraction of the two types of insulin used

54
Q

The use of premixed pens is viewed … by patients.

However, they are … common

A

The use of premixed pens is viewed positively by patients. However, they are less common.