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Endocrine System > Insulin Preparations for Diabetes Mellitus Therapy > Flashcards

Insulin Preparations for Diabetes Mellitus Therapy Flashcards

1
Q

What do alpha cells secrete?

A

Glucagon

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2
Q

What is the function of Glucagon?

A

Increase blood glucose

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3
Q

What do beta cells secrete?

A

Insulin and amylin

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4
Q

What is the function of Insulin?

A

Decrease blood glucose

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5
Q

What is the function of amylin?

A

Suppress glucagon release; delay gastric emptying and decrease food intake

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6
Q

What do delta cells secrete?

A

Somatostatin

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7
Q

What is the function of somatostatin?

A

Inhibit insulin & glucagon secretion

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8
Q

What do F cells secrete?

A

Pancreatic polypeptide

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9
Q

What is the function of pancreatic polypetide?

A

Unknown

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10
Q

What is C-peptide used as?

A

used as marker for insulin secretion (can help distinguish between different types of diabetes)

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11
Q

What is the main factor that controls the synthesis and secretion of insulin?

A

Blood glucose concentration

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12
Q

What are the nutrient stimulants of insulin synthesis and secretion?

A

Glucose, amino acids, and fatty acids

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13
Q

What are the nutrient inhibitors of insulin synthesis and secretion?

A

Chronic elevations in glucose and fatty acids

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14
Q

what are hormone stimulants of insulin synthesis and secretion?

A

Glucagon-like polypeptide (GLP-1) and Glucose-dependent insulinotropic polypeptide (GIP)

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15
Q

What are the hormone inhibitors of insulin synthesis and secretion?

A

Somatostatin

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16
Q

What are the neural stimulants of insulin synthesis and secretion?

A

Parasympathetic (Vagal) activation

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17
Q

What are the neural inhibitors of insulin synthesis and secretion?

A

Sympathetic (alpha-2 receptor) activation

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18
Q

What are then drugs stimulants of insulin synthesis and secretion?

A

Sulfonylureas, meglitinide, nateglinide

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19
Q

What are the drug inhibitors of insulin synthesis and secretion?

A

Diaxozide

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20
Q

What is the insulin release like from beta cells (in low concentration of glucose) ?

A
  1. Low glucose
  2. Low ATP
  3. The ATP-sensitive K+ channels open when low concentrations of ATP
  4. The K+ leaves the cell, and it reaches the resting membrane potential
  5. The Ca2+ channels stay closed, and no calcium enters the cell
  6. No exocytosis is triggered and the insulin remains in the vesicles
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21
Q

Where is GLUT 5 found?

A

Gut and kidney

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22
Q

What is the function of GLUT5?

A

Absorption of fructose

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23
Q

What is insulin?

A

Anabolic hormone –> required for normal growth and protein synthesis

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24
Q

When is insulin secreted?

A

In response to increased blood glucose levels

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25
Q

How does insulin lower blood glucose levels?

A
  1. Increase in GLUT 4 mediated glucose uptake & utilization in skeletal muscle and adipose tissue
  2. Inhibition of liver gluconeogenesis and glycogenolysis and prevention of glucose release from the liver into the blood
  3. Stimulation of glycogen production, protein synthesis and triglyceride formation in target organs
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26
Q

What are the effects of insulin on the liver? (7)

A

Increase glycolysis
Increase glycogenesis
Decrease gluconeogenesis
Decrease glycogenolysis
Increase lipogenesis
Decrease lipolysis
Decrease protein breakdown

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27
Q

What are the effects of insulin on the adipose tissues? (5)

A

Increase glucose uptake
Increase glycerol synthesis
Increase triglyceride synthesis
Increase fatty acid synthesis
Decrease lipolysis

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28
Q

What are the effects of insulin on the skeletal muscle? (5)

A

Increase glucose uptake
Increase glycolysis
Increase glycogenesis
Increase amino acid uptake
Increase protein synthesis

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29
Q

Where is insulin secreted from?

A

Beta cells of Langerhans

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30
Q

What is insulin synthesized from?

A

Two precursors (preproinsulin and proinsulin)

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31
Q

What is insulin stored as?

A

Hexamers in secretory vesicles

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32
Q

How does insulin circulate?

A

As a free monomer with a half-life of about 5 minutes

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33
Q

Where does the degredation of insulin occur?

A

In the liver (60%) by Thiol metalloproteinase
In the kidney (40%) in the renal tubulses

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34
Q

Why is exogenous insulin usually administered parenterally?

A

Usually given as an SC injection because insulin is a protein that is rapidly degraded ORALLY

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35
Q

How can we measure insulin levels in blood when its half-life is only 5 minutes?

A

C-peptide has relatively longer half-life and it is used as a marker for insulin secretion

36
Q

What is the half-life of C-peptide?

A

About 30 minutes

37
Q

What insulin formulations were previously used clinically in humans?

A

Porcine and bovine but now “human” insulin made by recombinant technology is used instead

38
Q

How is recombinant technology used for insulin formulations?

A

Amino acid sequence of insulin is being altered to produce analogues of insulin, which differ in their rate of absorption from the site of inection

39
Q

How can the duration of action of short-acting, unmodified insulin be extended?

A

It can be extended by the addition of protamine and zinc at neutral pH or excess zinc ions

40
Q

What is the appearance of the modified “depot” insulins?

A

It goes from a clear solution to cloudy preparations

41
Q

What are the classifications of insulin preparations? (5)

A
  1. Rapid-acting (very fast onset & short duration)
  2. Short-acting (rapid onset of action)
  3. Intermediate-acting (intermediate onset & duration)
  4. Long-acting (slow onset and long duration)
  5. Pre-0mixed Insulins (Intermediate and rapid/short-acting insulin)
42
Q

What are examples of rapid-acting insulins?

A

Insulin lispro
Insulin aspart
Insulin glulisine

43
Q

What are examples of short-acting insulins?

A

Regular soluble insulin

44
Q

What are examples of intermediate-acting insulins?

A

Neutral Protamine Hagedorn or Isophane (NPH) insulin

45
Q

What are examples of long-acting insulins?

A

Insulin glargine
Insulin detemir
Degludec (Ultra-long acting)

46
Q

What are examples of the Pre-mixed insulins?

A

70 NPH/30 Regular
70 NPA/30 Aspart
75 NPL/25 Lispro

47
Q

What are the properties of rapid-acting insulins?

A

Amino acids are modified to favor dissociation and aid absorption from the injected site

48
Q

What are the properties of short-acting insulins?

A

Contains small amounts of zinc to improve stability and shelf-life

49
Q

What are the properties of intermediate-acting insulins?

A

Complexed with protamine to delay absorption from injected site

50
Q

What are the properties of long-acting insulins?

A

Amino acids are modified to delay absorption from injected site

51
Q

What is the administration of rapid-acting insulins like?

A

Insulin is administered as a monomer, and it can go into the bloodstream straight away and thus act rapidly

Mimics beta cell release of insulin in response to a meal

52
Q

At what pH is Insulin Glargine formulated?

A

pH 4

53
Q

What is the administration of Insulin Glargine like?

A

It forms micro-precipitates at the physiological pH of SC tissue, which delays its absorption from the injection site

To provide a constant low-level of insulin

54
Q

Which type of insulins can be administered before meal?

A

Prandial:
1. Regular (30 minutes before)
2. Lispro (Just before meal)
3. Aspart (Just before meal)
4. Glulisine (ust before meal)

55
Q

When are Basal Insulins given?

A

Once or twice daily

56
Q

Which is the insulin choice in pregnancy?

A

NPH

57
Q

Which basal insulins have low risk of nocturnal hypoglycemia compared to NPH?

A

Glargine
Detemir

58
Q

When is Degludec given?

A

Once daily or thrice weekly

59
Q

What are the clinical uses of insulin?

A

For the treatment of both Types 1 and 2
Short-acting (regular) insulin –> for the management of diabetic ketoacidosis

60
Q

What are the adverse effects of insulin ?

A

Hypoglycemia
Weight gain
Lipodystrophy (atrophy of subcutaneous fat at the site of inaction)
Hypersensitivity (with local urticaria; rarely, anaphylaxis might occur)

61
Q

What are the signs and symptoms of hypoglycemia?

A

Tachycardia
Palpitations
Sweating
Nausea
Hunger
May progress to convulsion and coma

62
Q

What are the insulin regimens like?

A

–> The majority of patients will require more than one daily injection, however, a once a day intermediate injection may be effective
–> Twice-daily mixtures of short and intermediate-acting insulin are commonly used

63
Q

What regimen is often given in the morning and what is it followed by?

A

Short and intermediate-acting insulin in the morning
Followed by further doses of short-acting given before lunch and dinner and an evening dose of intermediate-acting insulin given at bedtime

64
Q

What is the action of long-acting basal-analogues of insulin like?

A

Onset: 2 hours
Peak: none
Duration: 18 to 24 hrs

65
Q

What is the action of rapid-acting insulin-analogues like?

A

Onset: 0 to 15 minutes
Peak: 1 to 2 hours
Duration: 3 to 5 hours

66
Q

What is the action of intermediate human isophane insulin like?

A

Onset: -
Peak: 4 to 8 hours
Duration: 14 to 16 hours

67
Q

When are rapid-acting insulins taken?

A

Just before a meal or to lower blood glucose levels

68
Q

When are short-acting insulins taken?

A

30 minutes before a meal or to lower blood glucose levels

69
Q

When are intermediate-acting insulins taken?

A

Bedtime, or twice a day (morning and night)

70
Q

When are extended long-acting analogues taken?

A

Usually once or twice daily

71
Q

When are premixed analogues taken?

A

Depends on the combination

72
Q

What is the self-care of diabetes like?

A

Patients should be educated to practice self-care:
1. Blood-glucose monitoring
2. Body weight monitoring
3. Foot-care
4. Personal hygiene
5. Healthy lifestyle
6. Identify targets for conrol
7. Smoking cessation

73
Q

What is inhalable insulin?

A

Afrezza
Human insulin product that is rapidly absorbed upon inhalation

74
Q

Who is inhalable insulin for?

A

For patients searching for non-parenteral insulin to take just before meals

75
Q

What is the Pk of inhalable insulin like?

A

More closely resembles ultra-short-acting insulin

76
Q

What may inhalable insulin cause?

A

Bronchospasms or cough (contraindicated in asthma and COPD)

77
Q

How is inhalable insulin used in patients with Type 1 diabetes?

A

Must be used in combination with long-acting insulin

78
Q

How is inhalable insulin used in patients with Type 2 diabetes?

A

COmbination with other anti-diabetes drugs

79
Q

What are the different stages of Type 1 diabetes?

A

Stage 1
Stage 2
Stage 3

80
Q

What is stage 1 of type 1 diabetes like?

A

An asymptomatic period defined by seroconversion with the presence of at least two diabetes-related autoantibodies but preserved normoglycemia

81
Q

What is stage 2 of type 1 diabetes like?

A

Characterized by asymptomatic progression to dysglycemia

82
Q

What is stage 3 of type 1 diabetes like?

A

Onset of clinical disease and is defined by glycemic criteria

83
Q

What is Teplizumab therapy like?

A

Humanized, anti-CD3 monoclonal antibody, which is the only therapy with regulatory approval in the US for delaying the onset of clinical type 1 diabetes in individuals with the PRECLINICAL disease

84
Q

What is Teplizumab therapy approved for?

A

For individuals aged 8 years or older who have stage 2 diabetes and in administered as a single 14-day course of daily IV infusions

85
Q

What is the MOA of Teplizumab?

A

A monoclonal antibody that improves beta cell function via binding to the CD molecules on the surface of CD4+ and CD8+ T cells, both of which are involved in the destruction of pancreatic beta cells

86
Q

What are the adverse effects of Teplizumab?

A

Transient lymphopenia,
Rash,
Anemia,
Fever

87
Q
A

Endocrine System (25 decks)

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