Insulin 2 - Insulins Flashcards
(28 cards)
How do insulin formulations differ from eachother?
Differ in time to onset of activity, duration of action, and solubility characteristics
Pharmacokinetic profile of insulin formulations are altered by….
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)
Origin of insulin?
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
What are the ultra short acting insulins?
Lispro
Aspart
Glulisine
What are the short acting insulins?
Regular insulin
What are the intermediate acting insulins?
NPH (protamine)
What are the ultra long acting insulins?
Glargine
Detemir
How is insulin glulisine modified?
Lys for ASN at B3 and Glu for Lys at B29
How is insulin detemir modified?
14 fatty acid chain (myristic acid) is added to lysine at position 29 and Thr at position 30 is missing
How is insulin lispro modified?
Lys and Pro at 28 and 29 are flipped (Pro at 29, Lys at 28)
How is Insulin aspart modified?
Asp at position 28 instead of pro
How is insulin glargine modified?
Addition of Arg and Arg at positions 31 and 32 of beta chain
Substitution at position 21, put Glycine instead of Asn
How is porcine insulin modified?
Ala at position 30 instead of Thr
How is bovine insulin modified?
Ala at position 30 instead of Thr
What is the onset, peak, and duration of the ultra short acting insulins?
(Lispro, aspart, glulisine - all solutions)
Onset 0.25 hours (15 mins)
Peak 1-2 hours
Duration 4 hours
What is the onset, peak, and duration of the Short acting insulins?
(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
What is the onset, peak, and duration of the intermediate insulins?
NPH (Humulin N, Novolin N - all suspensions)
Onset: 1-3 hours
Peak: 6-14 hours
Duration of action: 18-24 hours
What is the onset, peak, and duration of the long acting insulins?
(Glargine, Detemir)
Onset: G 2-4, D 5-6
Peak: None
Duration: G 24, D 22-23
What is Afreeza?
Inhaled human insulin powder
Launched Feb 2015
Short acting insulin
How is Afreeza administered?
Inhaled powder
Take directly before meals
Used for both T1 and T2
Requires use with a long acting insulin
Cautions with Afreeza?
Contraindicated in respiratory disease and smoking
Requires FEV1 test before use
How do we dose insulin to mimic normal insulin activity in the body?
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
Indications for insulin?
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)
What drugs will decrease hypoglycemic effect of insulin?
Oral contraceptives Corticosteroids Dobutamine, epinephrine (stimulate breakdown of glycogen to glucose) Niacin Smoking Thiazides Thyroid hormones
All of these will elevate glucose levels
