Pharm of Insulin and Diabetes: Cook

Question 1

Explain the glucose tolerance test and A1c number.

Answer 1

The GTT is done as follows:
75g of glu are administered to the pt orally and after two hours, blood glu is measured.
glu 140-199mg/dl is prediabetes
glu >199mg/dl is diabetes

HbA1c is a measure of glycosylated Hb and is an indicator of plasma glucose levels throughout the life of that RBC (~120 days). Normal is 4-5.6%. Prediabetes is 5.7-6.4%. Diabetes is > 6.4%.

Question 2

Describe the different formulations of insulin for therapy.

Answer 2

Short acting insulin, “regular insulin”, is administered IV in the hospital for acute attacks of ketoacidosis. Made up of small crystals. It has a short half-life. It is the only formulation that can be administered IV.

Intermediate acting insulin:
Neutral, Protamine, Hagdorn (NPH)
Longer acting b/c large crystals, longer half-life.

Question 3

Discuss insulin replacement therapy.

Answer 3

Need 4, meals a day (4th meal: high carb load).
Measure plasma glu before each meal.
Combine short-long acting insulins after breakfast and lunch AFTER glu measurement.
Long-acting after 4th meal.

Adjustments based on glu measurements before meal:
Too high before breakfast, incr. 4th meal NPH dose.
Too high before lunch, incr. breakfast regular dose.
Too high before dinner, incr. breakfast dose of NPH.
Too high before 4th meal, incr. dinner regular dose.

Decrease insulin if glu is too low to prevent hypoglycemia (emergency!)

Question 4

Describe the different types of human insulin and human insulin analogs.

Answer 4

Human insulin is produced in two ways:
::Humulin is made using recombinant DNA to make the hormone in yeast or bacteria.
::Novolin is another recombinant human insulin

Human insulin analogs:
Insulins lispro, aspart, and glulisine - don’t form hexamers in the blood like normal human insulin, therefore more soluble and have faster onset of action, and shorter half-lives.

Question 5

Describe insulin hexamer formation.

Answer 5

Normal endogenous insulin forms hexamers (less soluble) in the blood because of zinc found in the blood. Human insulin analogs such as lispro, aspart, and glulisine do not form these hexamers and are more soluble.

Question 6

Discuss the advantages of synthetic insulins that have shifted isoelectric points.

Answer 6

Insulins having an altered isoelectric point, such as glargine and detemir, rDNA human insulin analogs, will go from being soluble in their vials to precipitating crystals once neutralized in the blood. These crystals work like NPH insulin in that they take a while to dissolve and thus are long acting. Only have to be injected once a day.

Question 7

Describe the advantages and difficulties in therapeutics of inhaled insulin powders.

Answer 7

Short-acting
Easier to admin
Used in T1DM or T2DM
Replaces meal-time injections.

Expensive
Not a complete replacement for insulin therapy.
Use precluded in lung pathology.

Question 8

Describe the advantages and limitations of the insulin pump.

Answer 8

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Question 9

Distinguish between diabetic coma and hypoglycemic coma.

Answer 9

Diabetic coma (ketoacidosis):
::due to low insulin (kills you slow)
::effects of low insulin exaggerated by cortisol, GH, glucagon, catecholamines
::Increased release of FFA causes increased ketone bodies and further decreased pH
::Hyperglycemia due to hepatic gluconeogenesis
::Tx: insulin

Hypoglycemic coma:
::due to insulin OVERDOSE (kills you fast)
::So common that all comatose pts are given glucose while blood glu is being measured.
Tx: glucose- literally wakes them right up!

Question 10

Quick review of time of action of various insulin formulations:

Answer 10

Aspart, lispro, glulisine: 4-6 hrs (short acting)
Regular, endogenous or exogenous: 6-10 hrs
NPH: 12-20 hrs (intermediate acting)
Ultralente: 18-24 hrs (long acting)
Glargine: 20-28 hrs (long acting)