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Pharm Exam 3 > Insulin > Flashcards

Insulin Flashcards

1
Q
  • Insulin nearly absent
  • Autoimmune destruction of pancreatic B cells
  • Plasma glucagon elevated
  • Occurs mainly in adolescents
A

Type I diabetes

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2
Q

Exogenous insulin given to type I diabetes patients for what?

A
  1. Prevent ketosis
  2. Reduce hyperglucagonemia
  3. Reverse catabolic state
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3
Q
  • Abnormal insulin secretion and resistance to insulin action at tissues
  • Associated with obesity and metabolic syndrome
  • Deficiency in pancreatic B cell response to glucose, worsened by hyperglycemia
A

Type II diabetes

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4
Q

How do you treat Type II diabetes in the early and late stages?

A

Early: Noninsulin anti diabetic drugs

Late: Drug regimen with addition of insulin

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5
Q

Type _____ diabetes is caused by elevated blood glucose due to other reasons such as pancreatectomy, pancreatitis, non pancreatic disease, drug therapy, etc.

A

3

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6
Q
  • Gestational diabetes
  • Abnormality in glucose levels beginning during pregnancy (7%)
  • Placenta/placental hormones creaste insulin resistance (most prominent in last trimester)
A

Type 4 diabetes

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7
Q

HbA1c tests for what?

A
  • A1c measures the “glycosylated” hemoglobin
  • A1c is correlated with mean blood glucose

Pt at goal: test 2xs a year
Pt not at goal: test 4xs a year

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8
Q

What is the stepped care approach for type 2 diabetes?

A
  1. Lifestyle changes: diet, exercise, smoking, lipids
  2. Single oral agent
  3. Combination oral therapy
  4. Oral therapy plus insulin
  5. Insulin
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9
Q

How is insulin formed?

A

Proinsulin produced by pancreatic B cells are packaged into granules where its hydrolyzed into insulin and C peptide. Insulin is stored in crystals with a ratio of 2 atoms of zinc with 6 atoms of insulin

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10
Q

Insulin high secretion rate is released in response to what 4 factors?

A
  1. Glucose
  2. Other sugars (ex: Mannose)
  3. Certain amino acids (ex: Leucine, arginine)
  4. Vagal nerve activity
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11
Q

Give MOA of Insulin.

A
  1. Hyperglycemia
  2. Increased intracellular ATP
  3. Higher intracellular ATP closes ATP-dependent K+ channels
  4. Decrease in outward K+ movement causes depolarization which opens calcium channels
  5. Increase in intracellular calcium
  6. Intracellular 2nd messengers modulate release of cyclic AMP (cAMP), inositol triposphate (IP3), and diacylglycerol (DAG).
  7. Release of Insulin
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12
Q

What organ/organs clears insulin from the body?

A
  • Liver: 60% of insulin released from pancreas
  • Kidney: 35-40% of endogenous insulin (in insulin-treated diabetics - subcutaneous injections - the kidney may clear as much as 60%)
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13
Q

How is insulin degraded?

A

Cleavage of sulfide linkage between A and B chains space and then further degraded by proteolysis

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14
Q

What is the composition of insulin?

A

Two heterodimers that contain an alpha subunit (extracellular: recognition site) and a beta subunit that spans the membrane and contains a tyrosine kinase..

The subunits combine to form either homodimers or heterodimers, resulting in the disulfide-linked transmembrane insulin receptor.

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15
Q

Insulin binds to ___ subunit.

A

Alpha

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16
Q

___ subunit increases tyrosine kin as activity, resulting in auto-phosphorylation.

A

Beta

-Phosphorylated beta subunit promotes aggregation of heterodimers and stabilizes the receptor kinase activated state

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17
Q

What causes a change in the affinity of insulin receptors?

A
  • Decreased affinity: caused by some hormonal agents (hydrocortisone)
  • Increased affinity: caused by growth hormone
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18
Q

What glucose transporter is most important in lowering blood glucose and where does it act?

A

GLUT4 - found in muscle and adipose cell membranes and is inserted from storage vesicles.

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19
Q

Where are GLUT2 glucose transporters found?

A

Pancreatic B cells and liver

-Abnormalities in these transporters may contribute to reduced insulin secretion in type 2 diabetes

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20
Q

Endogenous insulin reaches the liver first. What does it do in the liver?

A

Increases glucose storage as glycogen through the insertion of additional GLUT2 glucose transport molecules in cell plasma membrane

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21
Q

Insulin resets liver to “fed” stat which influences what factors?

A
  1. Glycogenolysis
  2. Ketogenesis
  3. Gluconeogenesis

Also causes decreased protein catabolism.

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22
Q

What are the actions insulin has on muscle cells?

A
  1. Protein synthesis

2. Glycogen synthesis (Glucose transport into muscle cells facilitates GLUT 4 transporters into plasma membrane)

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23
Q

What are the actions of insulin on adipose cells?

A

Reduces free fatty acids in circulation by promoting triglyceride storage via these 3 mechanisms:

  1. Lipoprotein Lipase induction
  2. Enhance glucose transport (GLUT4 transporters)
  3. Reduces intracellular lipolysis of stored triglyceride
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24
Q

Goal in treating insulin is to control both basal and postprandial (after meal) glucose levels, minimizing _____________.

A

Hypoglycemia

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25
Q

What are the rapid-acting insulins?

A
  • Insulin lispo
  • Insulin aspart
  • Insulin glulisine
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26
Q

When are Insulin lispro peak serum values?

A

Within 1 hr - much more rapid than hexametric human insulin.

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27
Q

New, monomeric insulin analog, recombinant technology, interchange of two amino acids near the B chain terminal, rapid acting

A

Insulin Lispro

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28
Q

When should Insulin Lispro be given?

A
  • Injected immediately before a meal (Postprandial glucose control)
  • Preferred for infusion devices
  • Duration of action is no more than 3-4 hours
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29
Q

What is a short-actin insulin drug?

A

Regular insulin (Novolin R)

30
Q

Short-acting, soluble crystalline, zinc insulin with onset of 1 hour and duration of 5-6 hours

A

Regular insulin

31
Q

What is Regular insulin used for?

A
  1. IV treatment for diabetic ketoacidosis
  2. Administered subcutaneously alone or mixed with intermediate or long-acting preparations for management for rapidly changing insulin requirements (post surgery, acute infection)
32
Q

What are the intermediate and long-acting insulins?

A
  • NPH (neutral protamine Hagedorn) insulin
  • Insulin glargine
  • Insulin detemir
  • NPL (neutral protamine lispro)
  • NPA (neutral protamine aspart)
  • Human insulins
33
Q

________ is a highly basic protein that is used to reverse the action of unfractionated heparin.

A

Protamine

34
Q

The onset of _____ can be delayed by combining correct amounts of regular insulin and protamine such that neither is uncomplexed.

A

NPH

  • Onset and peak action delayed
  • Usually mixed with regular and rapid-acting insulin for twice daily administration
  • Variable action and absorption decrease its clinical use
35
Q

This drug has modifications that allow for a low, continuous level of circulating insulin that can last 11-24 hours.

A

Insulin glargine

36
Q

This drug is the most recently developed drug that has modifications to prolong the availability of the injected analog by increasing self-aggregation and albumin binding. It has the most reproducible effect of the intermediate/long acting insulins.

A

Insulin detemir

37
Q

__________ produces less hypoglycemia than NPH and is given twice daily to obtain constant basal insulin levels

A

Insulin detemir

38
Q

_____ and ____ are mixtures of 50/50 rapid with intermediate acting insulin. Need sustained insulin control but the addition of the rapid insulin gives post prandial control.

A

NPL & NPA

39
Q

What are the advantages of human insulin?

A

Less immunogenic than beef-pork insulin

40
Q

What types of insulin drugs are now recombinant DNA human insulins?

A

Regular, NPH, lente, or ultralente form

41
Q

What are CSII or insulin pumps?

A

Continuous subcutaneous insulin infusion devices used to control blood glucose. Basal rates are preprogramed and posprandial control can be programmed from algorithms based on carbohydrates consumed.

42
Q

What percentage of diabetics (type I and II) can use insulin as a treatment option?

A
  • Type I = 9%

- Type II = 20%

43
Q

What is diabetic ketoacidosis?

A

Life-threatening emergency caused by inadequate or absent insulin replacement. When insulin isn’t there to intake glucose, the body starts using fatty acids for energy causing ketone body formation.

Treatment: Aggressive IV hydration and insulin therapy

44
Q

What is hyperosmolar hyperglycemic syndrome?

A

Can occur in patients with type 2 diabetes if the insulin given is sufficient to prevent ketosis but not enough to control hyperglycemia.

Results from sustained hyperglycemia diuresis if the patient cannot drink enough water to keep up with the urinary fluid loss.

Treatment: Aggressive rehydration and restoration of glucose homeostasis.

45
Q

What is the most common complication of insulin treatment and what is it caused by?

A

Most common complication is hypoglycemia

Caused by: delay in eating, unusual physical exertion, and inappropriately high insulin dosage for the immediate need

46
Q

What are some of the manifestations of hypoglycemia?

A

Tachycardia, palpitations, sweating, tremor, nausea, hunger

Autonomic hyperactivity

47
Q

Indications of hypoglycemia are less frequently perceived by elderly patients because…?

A

They may exhibit impaired CNS function

48
Q

How do you treat hypoglycemia?

A

Glucose administration - orange juice, glucose, sugar containing beverage and food

49
Q

How do you treat a hypoglycemic person who is unconscious?

A
  • IV infusion (50% glucose solution over a 2-3 minute interval)
  • In absence of IV infusion, 1 mg of glucagon (subcutaneous of IM administration) should restore consciousness within 15 mins (then allow food consumption)
50
Q

If theres a hypertrophy of subcutaneous fatty tissue due to insulin being injected repeatedly at the same site is there anyway to correct this?

A

Yes, Liposuction can correct it - (injection site lipodystrophy)

51
Q

What are the 4 major oral hyperglycemics?

A
  1. Secretagogues
  2. Biguanides
  3. Alpha-glucosidase inhibitors
  4. Thiazolidinediones
52
Q

What are sulfonylureas and what are the mechanism of actions?

A

They are insulin secretagogues

  • Primary MOA: Promotion of insulin release for B cells (bind to pancreatic B cell K+ channel receptor causing K+ blockage and cell depolarization)
  • Secondary MOA: Reduction of serum glucagon concentration
53
Q

What are the first generation sulfonylureas?

A
  • Tolbutamide
  • Chlorpropamide
  • Tolazamide
54
Q

What is the safest sulfonylurea used in the elderly?

A

Tolbutamide

55
Q

When treating a patient with tolbutamide there have been rare cases of prolonged hypoglycemia usually due to drug interactions with which drugs?

A

Dicumerol, phenylbutazone, or some sulfonamides

56
Q

Which sulfonylurea is generally not recommended because of the vast side effects?

A

Chlorpropamide

Hypoglycemic risk results in this drug typically being an unacceptable choice for elderly patients and those with mild to moderate hepatic and ranal dysfunction.

57
Q

This drug causes dilution hyponatremia - results from enhanced vasopressin secretion and potentiation of its effects at the renal tubule.

A

Chlorpropamide

58
Q

This drug is comparable to chlorpropamide in potency but wit a shorter duration of action. It is slowly absorbed and has delayed effects on blood glucose.

A

Tolzamide

59
Q

What are some second generation sulfonylureas?

A
  • Glyburide
  • Glipizide
  • Glimepiride
60
Q

Why are second generation sulfonylureas more commonly prescribed?

A

Fewer adverse effects.

61
Q

This drug is metabolized in the liver, short plasma half-life but prolonged biological effect, does not cause water retention and is a second gen.

A

Glyburide

62
Q

When is glyburide contraindicated?

A
  1. Hepatic impairment

2. Renal insufficiency

63
Q

What drug has the shortest half life, has extended release formation (24 hr action), and is less likely than glyburide to produce serious hypoglycemia?

A

Glipizide

Contraindicated in patients with hepatic dysfunction and renal insufficiency

64
Q

Of the Sulfonylureas which is the most potent and therefore is given as the lowest dose once a day (monotherapy)?

A

Glimepiride

Has a long duration of action. Half life = 5 hours

65
Q

What are Glitinides?

A

Insulin secretagogues very similar to sulfonylureas with overlap in binding sites, closed K-ATP channels.

66
Q

What are 2 drugs in the Glitinide class?

A
  • Repaglinid

- Nateglinide

67
Q

_______________ is a meglitinide insulin secretagogue that has a fast onset of action with a duration of 4-7 hours and is approved as a mono therapy or in combo with biguanides.

A

Repaglinide

68
Q

When given this drug the incidence of hypoglycemia may be the lowest of all secretagogues and is safe in those with severely reduced renal function but it only treats postprandial hyperglycemia with minimal fasting glucose level control.

A

Nateglinide

69
Q

What drug is used as a first choice in overweight patients with type 2 diabetes and why?

A

Metformin

-Used bc it does not cause hypoglycemia and does not cause increased weight gain.

70
Q

This drug is also used to restore fertility in anovulatory women with polysystic ovary disease.

A

Metformin

71
Q

Metformin causes decreased ____ absorption. (vitamin)

A

Vitamin B12

Vitamin B12 supplementation should be used

Pharm Exam 3 (4 decks)

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