Insulin 2 - Insulins

Question 1

How do insulin formulations differ from eachother?

Answer 1

Differ in time to onset of activity, duration of action, and solubility characteristics

Question 2

Pharmacokinetic profile of insulin formulations are altered by….

Answer 2

Varying zinc concentration (no longer available...? idk what he means by this)
Adding protamine (NPH, NPL)
Insulin analogs: Lispro, aspart, glulisine (shorter duration) or glargine, detemir (long duration)

Question 3

Origin of insulin?

Answer 3

Older insulins use beef, pork, or beef/pork mixture
Beef no longer available bc it was antigenic, pork only available by special order

Now we use human insulin, recombinant in E coli or yeast
E coli = humulin
Yeast = novolin

Question 4

What are the ultra short acting insulins?

Answer 4

Lispro
Aspart
Glulisine

Question 5

What are the short acting insulins?

Answer 5

Regular insulin

Question 6

What are the intermediate acting insulins?

Answer 6

NPH (protamine)

Question 7

What are the ultra long acting insulins?

Answer 7

Glargine

Detemir

Question 8

How is insulin glulisine modified?

Answer 8

Lys for ASN at B3 and Glu for Lys at B29

Question 9

How is insulin detemir modified?

Answer 9

14 fatty acid chain (myristic acid) is added to lysine at position 29 and Thr at position 30 is missing

Question 10

How is insulin lispro modified?

Answer 10

Lys and Pro at 28 and 29 are flipped (Pro at 29, Lys at 28)

Question 11

How is Insulin aspart modified?

Answer 11

Asp at position 28 instead of pro

Question 12

How is insulin glargine modified?

Answer 12

Addition of Arg and Arg at positions 31 and 32 of beta chain
Substitution at position 21, put Glycine instead of Asn

Question 13

How is porcine insulin modified?

Answer 13

Ala at position 30 instead of Thr

Question 14

How is bovine insulin modified?

Answer 14

Ala at position 30 instead of Thr

Question 15

What is the onset, peak, and duration of the ultra short acting insulins?

Answer 15

(Lispro, aspart, glulisine - all solutions)

Onset 0.25 hours (15 mins)
Peak 1-2 hours
Duration 4 hours

Question 16

What is the onset, peak, and duration of the Short acting insulins?

Answer 16

(Regular insulin - humulin R, Novolin R, Velolusin BR, Exubra (d/c 2007))

Onset 30 mins to 1 hour
Peak 2-4 hours
Duration 5-7 hours

Note exubra is a dry powder that was d/c in 2007
Velolusin is an insulin pump

Question 17

What is the onset, peak, and duration of the intermediate insulins?

Answer 17

NPH (Humulin N, Novolin N - all suspensions)

Onset: 1-3 hours
Peak: 6-14 hours
Duration of action: 18-24 hours

Question 18

What is the onset, peak, and duration of the long acting insulins?

Answer 18

(Glargine, Detemir)

Onset: G 2-4, D 5-6
Peak: None
Duration: G 24, D 22-23

Question 19

What is Afreeza?

Answer 19

Inhaled human insulin powder
Launched Feb 2015
Short acting insulin

Question 20

How is Afreeza administered?

Answer 20

Inhaled powder
Take directly before meals
Used for both T1 and T2
Requires use with a long acting insulin

Question 21

Cautions with Afreeza?

Answer 21

Contraindicated in respiratory disease and smoking

Requires FEV1 test before use

Question 22

How do we dose insulin to mimic normal insulin activity in the body?

Answer 22

Usually use a short acting insulin before meals, and use a long acting insulin twice daily (to mimic basal insulin secretion)

Note: Normal insulin is usually a biphasic response, can’t really get that with the injections

Question 23

Indications for insulin?

Answer 23

All newly diagnosed T1 DM patients
Pregnant women with T2DM or women who develop gestational DM
Type 2 DM not controlled by diet, exercise, PO meds
Diabetic ketoacidosis
Hyperglycemic hyperosmolar nonketotic coma (HHNC)
Hyperkalemia (shifts potassium into the cell)

Question 24

What drugs will decrease hypoglycemic effect of insulin?

Answer 24

Oral contraceptives
Corticosteroids
Dobutamine, epinephrine (stimulate breakdown of glycogen to glucose)
Niacin
Smoking
Thiazides
Thyroid hormones

All of these will elevate glucose levels

Question 25

What drugs will potentiate hypoglycemic effect of insulin?

Answer 25

Alcohol
Alpha-blockers
Anabolic steroids
Beta blockers
MAO inhibitors

Question 26

Complications of insulin use?

Answer 26

Hypoglycemia
Weight gain
Immunopathology (insulin allergy, IgE mediated or immune insulin resistance, IgG mediated)
Lipodystrophy at injection sites

Question 27

Goals of therapy with insulin?

Answer 27

Maintain blood glucose in acceptable range to prevent hyperglycemia
Prevent long term microvascular complications
Minimize incidence of hypoglycemia

Question 28

Goal fasting plasma glucose?
Goal postprandial glucose?
Goal glycosylated hemoglobin (a1c)?

Answer 28

Fasting: 80-120
Postprandial: 100-140
A1C: Less than 6.5%