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S3 Case 4 - Endocrine > Insulin Formulations > Flashcards

Insulin Formulations Flashcards

1
Q

What does it mean if it is more soluble?

A

Faster acting = shorter-acting

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2
Q

What is insulin self-association?

A

Monomers form dimers form hexamers

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3
Q

What is the most soluble?

A

Monomers = most
Dimers
Hexamers = least

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4
Q

How are subunits linked together?

A

By disulphide bridges

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5
Q

What are the interactions between?

A

Subunit B

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6
Q

What is insulin self-association linked with?

A

Equilibrium

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7
Q

What factors affect insulin self-association?

A

Relative concentration of each form
Excipients

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8
Q

What happens if there are more hexamers?

A

Equilibrium shifts so less hexamers = more monomers

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9
Q

What can modifying insulin structure cause?

A

High absorption rate = faster-acting
Lower absorption rate = lower-absorption rate

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10
Q

What is animal insulin?

A

Extracted + purified from bovine + porcine pancreas

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11
Q

What are the cons of animal insulin?

A

Some cultures NOT accepted

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12
Q

What is recombinant human insulin?

A

Structurally identical to human insulin
BUT produced in bioreactor using recombinant DNA technology

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13
Q

What is an example of recombinant human insulin?

A

Insuman

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14
Q

What is an example of animal insulin?

A

Hypurin

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15
Q

What do solutions tend to be?

A

Rapid onset, shorter-acting

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16
Q

What do suspensions tend to be?

A

Slower onset, longer-acting

17
Q

How do excipients influence duration?

A

Zinc + phenolic compounds promote self-association of insulin into hexamers

18
Q

What is NPH?

A

Neutral Protamine Hagedorn
= Isophane insulin (intermediate)

19
Q

How does NPH (isophane) insulin work?

A

Protamine complexes with insulin to form aggregates through ionic interactions = suspension
= prolongs insulin release

20
Q

What are the more soluble forms of insulin?

A

Lispro
Aspart
Glulisine

21
Q

What are the less soluble forms of insulin?

A

Degludec
Detemir
Glargine

22
Q

How does the change in Insulin Lispro make it faster-acting?

A

Destabilises dimers + hexamers
= monomers favoured
ALSO binds to zinc less avidly = doesn’t form dimers + hexamers

23
Q

How is Insulin Lispro formed?

A

Proline is swapped for lysine
Lysine is swapped for proline

24
Q

How is Insulin Aspart formed?

A

Proline swapped for aspartic acid

25
Q

How does the change in Insulin Aspart make it faster-acting?

A

Destabilisers dimers + hexamers
= monomers favoured

26
Q

How is Insulin Glulisine formed?

A

Asparagine swapped for lysine
Lysine swapped for glutamic acid

27
Q

How does the change in Insulin Glulisine make it faster-acting?

A

Decreased hexamer formation
Monomer stabilisation
Enhanced solubility

28
Q

How is Insulin Degludec formed?

A

Threonine removed
Attach hexadecandioyl through glutamic acid spacer at lysine

29
Q

What is an example of Insulin Degludec?

A

Tresiba

30
Q

How does the change in Insulin Degludec make it longer-acting?

A

Injected
As phenol from vehicle diffuses = insulin degludec hexamers link up via single side-chain contacts
= less soluble than hexamers
= long chain dissociates = releases insulin

31
Q

How is Insulin Detemir formed?

A

Remove threonine
Attach myristic acid at lysine

32
Q

How does the change in Insulin Detemir make it longer-acting?

A

Binds albumin
= makes it stay longer in blood
= prolonging t1/2

33
Q

How is Insulin Glargine formed?

A

Swap asparagine for glycine
Then add 2 arginine’s

34
Q

How does the change in Insulin Glargine make it longer-acting?

A

Changes isoelectric point to 6.7
= reduced solubility at physiological pH

35
Q

What is an example of Insulin Glargine?

A

Toujeo

36
Q

What is an example of Insulin Detemir?

A

Levemir

37
Q

What devices are there?

A

Insulin pen
Insulin pumps
Closed-loop systems
Inhaled insulin - Exubera (discontinued) + Afrezza

S3 Case 4 - Endocrine (17 decks)

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