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Therapeutics 2 Exam 2 -Diabetes > Insulins > Flashcards

Insulins Flashcards

1
Q

What is the main source of insulin?

A

Recombinant human insulin

-Plasmid is expressed in either E.coli or Transformed yeast (depending on company making it)

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2
Q

What are the advantages of using recombinant human insulin?

A

-No longer come from animal sources
-Pure (homogenous)
-Can control amino acid sequences (can make it rapid acting or slowly absorbed)
-Companies can produce large quantities of insulin

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3
Q

Is insulin absorbed well orally?

A

NO
-currently all forms of insulin available are injectable

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4
Q

Which forms of insulin have a VERY RAPID ONSET with a VERY SHORT ACTION?

A

-Lispro (Humalog)
-Aspart (Novolog)
-Glulisine (Apidra)

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5
Q

Which form of insulin has a RAPID ONSET with a SHORT ACTION?

A

Regular (R)

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6
Q

Which form of insulin has an INTERMEDIATE ONSET/ACTION

A

NPH (N)

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7
Q

Which forms of insulin have a SLOW ONSET with a LONG ACTION?

A

-Glargine (Lantus)
-Detemir (Levemir)
-Degludec (Tresiba)

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8
Q

How do the “lente” insulins work?

A

The insulin forms complexes with zinc to slow down its absorption
-the monomer is absorbed

Semilente: small particles, non-crystalline

Lente (L)- small particles, large crystalline complexes

Ultralente (U)- Only large crystalline complexes

(the bigger the complex, the slower the absorption and longer acting it is)

**NO LONGER USED THERAPEUTICALLY

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9
Q

What is the structure of the Insulin Hexamer Nucleated by Zinc?

A

Trimer of Dimers

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10
Q

Which of the insulins is NOT genetically modified?

A

NPH insulin

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11
Q

What is the structure of NPH insulin and how does this affect its absorption/duration of action?

A

-The insulin is bound to a protamine
- When it reaches the tissue, it must be released by proteases to form free insulin

*This insulin has:
–Slow Absorption
–Long Duration of Action

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12
Q

What is the structure of Lispro Insulin (Humalog) and how does this affect its absorption/duration of action?

A

-The positions of P28 (proline) and K29 (lysine) on the insulin beta chain are switched
-This prevents the dimer and hexamer formation typically seen in normal insulin

*This insulin has:
–Very Rapid Absorption
–Very Short Duration of Action

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13
Q

Which insulins should be injected immediately before meals?

A

-Lispro insulin (Humalog)
-Insulin Aspart (Novolog)
-Insulin Glulisine (Apidra)

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14
Q

When you want fast-acting insulin, what form should it be in?

A

The monomer form

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15
Q

When we want to interrupt dimerization of insulin, what part of the insulin structure do we target?

A

The beta chain

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16
Q

Which part of the insulin beta chain structure is important for complexing with zinc?

A

Histamine

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17
Q

What is the structure of Insulin Aspart (Novolog) and how does this affect its absorption/duration of action?

A

Proline 28 in the beta chain is changed to aspartate
-This disrupts dimerization of the insulin molecule

*This insulin has:
–Very Rapid Absorption
–Very Short Duration of Action

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18
Q

What is the structure of Insulin Glulisine (Apidra) and how does this affect its absorption/duration of action?

A

Asn 3 (asparagine) and Lys 29 (lysine) in the beta chain are switched to Lys (lysine) and Glu (Glutamic Acid)
-This disrupts dimerization of the insulin molecule

*This insulin has:
–Very Rapid Absorption
–Very Short Duration of Action

19
Q

What is the structure of Insulin Glargine (Lantus) and how does this affect its absorption/duration of action?

A

–Asn 21 (asparagine) in the ALPHA chain is changed to Gly (Glycine)
–2 Arg (arginine) residues are added to the end of the BETA chain

-When injected, the pH is around 7.2-7.3
–Glargine is not soluble at this pH (Solution at pH of about 4)
–Therefore, glargine is slowly released from the injection site

*This insulin has:
–Slow Absorption
–Long Duration of Action

20
Q

How long does it take for Glargine insulin (Lantus) to be absorbed?

A

24 hours
(Daily injection)

21
Q

What is a benefit to using Insulin Glargine (Lantus) vs NPH insulin when it comes to glucose utilization?

A

NPH insulin shows a pronounced peak in glucose utilization right after the medication is injected

Insulin Glargine (Lantus) does not have a pronounced a peak in glucose utilization and, instead, shows steady usage over time

*We do not want a peak!

22
Q

What is the structure of Insulin Detemir (Levemir) and how does it affect its absorption/duration of action?

A

Thr 30 (Threonine) is deleted in the beta chain and Lys 29 (Lysine) is myristylated (a fatty acid chain is attached)

-The fatty acid chain binds to serum albumin extensively

-The insulin is then slowly released from albumin over time

*This insulin has:
–Slow Absorption
–Long Duration of Action

23
Q

How often does Insulin Detemir (Levemir) need to be injected?

A

Once or Twice daily

24
Q

What is the structure of Insulin Degludec (Tresiba) and how does this affect its absorption/duration of action?

A

Thr (threonine) 30 in the beta chain is replaced by y-Glu/C16 fatty acid

–This fatty acid binds extensively to serum albumin

-The insulin is then slowly released from albumin over time

*This insulin has:
–Slow Absorption
–Long Duration of Action

25
Q

How often should Insulin Degludec (Tresiba) be injected?

A

Once daily

26
Q

What are the common multi-dose insulin regimens?

A

-A fast onset, short acting insulin taken before meals

WITH

-A long or intermediate acting insulin taken at bedtime OR taken at bedtime + after breakfast

27
Q

How do mixture products work?

A

-Combine a long-acting with a short-acting insulin into ONE injection

28
Q

What is Afrezza?

A

Regular human insulin in a dry powder that is INHALED

29
Q

What is the absorption and duration of action of Afrezza?

A

Rapid absorption/onset

Shorter duration of action than subcutaneous forms

30
Q

When should inhaled insulin be used?

A

Before a meal

31
Q

When is Afrezza (inhaled insulin) contraindicated?

A

In patients with asthma and COPD

**May reduce lung function (decreased FEV)

32
Q

Which insulins are administered using an infusion pump?

A

-Buffered Regular insulin
-Rapid Acting insulin (Lispro, Aspart, Glulisine)

33
Q

Which insulin is administered through IV?

A

Regular

34
Q

When would insulin be administered through an IV?

A

Severe hyperglycemia or ketoacidosis

35
Q

What does insulin do in diabetic patients?

A
  1. decreases liver glucose output
  2. increases fat storage
  3. increases glucose uptake
36
Q

What are the possible adverse reactions someone can have to insulin?

A

-Hypoglycemia
-Lipodystrophy
-Lipoatrophy
–Lipohypertrophy

37
Q

What is hypoglycemia and how is it treated?

A

Blood glucose < 60mg/dl
–caused by too much insulin or not enough food

-Treated with glucose OR glucagon

38
Q

Why is there increased sympathetic output when hypoglycemia occurs?

A

-Neural cells depend on blood glucose concentrations since they have constant glucose needs
-The brain tries to bring blood glucose levels back up by mobilizing glucose from the liver

39
Q

What is lipodystrophy?

A

A lump of fat that forms when an insulin injection site is over used

40
Q

What is lipoatrophy?

A

Concavities that form in subcutaneous tissue
(typically result from allergic reactions to insulin)

41
Q

What is lipohypertrophy?

A

The accumulation of fat in subcutaneous tissue

42
Q

What effect can ethanol have on blood glucose levels?

A

Brings blood glucose levels down
–Can increase the risk of hypoglycemia!

43
Q

What affect do beta blockers have on insulin patients who are hypoglycemic?

A

-Beta blockers can mask the side effects of hypoglycemia which may lead patients to not realize they are hypoglycemic until it gets really bad

Therapeutics 2 Exam 2 -Diabetes (4 decks)

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