14. Pharm - Insulin and Oral Hypoglycemics

Question 1

What happens to insulin if it loses its disulfide bridges?

Answer 1

Loss of functional activity of insulin

Question 2

Describe the insulin receptor

Answer 2

2 alpha, 2 beta subunits

Question 3

Four things that the membrane becomes permeable to after insulin binds:

Answer 3

Glucose, amino acids, potassium, phosphate

Question 4

Where does glucagon act? What does it do?

Answer 4

Liver
GNG, Glycogenolysis

(Inc. blood glucose levels)

Question 5

Where is somatostatin secreted from? What causes its secretion?

Answer 5

Anterior pituitary and delta cells

Inc. blood glucose, amino acid, FA, GI hormones cause somatostatin release

Question 6

Effects of somatostatin, esp in relation to GH

Answer 6

Inhibit glucagon and insulin secretion
Dec GI motility
Also called Growth Hormone Inhibitory Hormone in hypothalamus –> inhibits release of GH from ant pit

Question 7

Hyperinsulinism is caused by what?

Answer 7

Insulin secreting adenoma

Question 8

What are the three sources (species) that insulin comes from?

Answer 8

Porcine = pig
bovine = cow
human

Question 9

Advantages to using human insulin

Answer 9

less antigenic, lower titers of insulin antibodies, less allergies

Question 10

Insulin is classified by the time it takes for them to act. What are these classifications

Answer 10

Long acting, intermediate acting, short (rapid) acting, very short acting, and ultra rapid acting

Question 11

What is the long acting insulin? Duration and injections per day?

Answer 11

Ultralente
Duration: 24-36hrs
Injections: 1/day

Question 12

What is the intermediate acting insulin? Peak/duration/injections?

Answer 12

Neutral protamine hagedorn (NPH)
Mixture of long acting ultralente and short acting semilente

Peak: 10hrs
Duration: 12-24 hrs
Injections: 1-2/day

Question 13

Short acting insulin? Peak/duration/injections?

Answer 13

Semilente

Peak - 4hrs
Duration - 8hrs
Injections - 2-3injections/day

Question 14

Very rapid acting insulin (SE, duration)

Answer 14

Humalog
Analog of human insulin
15-30mins before meal

SE: Hypoglycemia, hypokalemia, weight gain, injection-site-reaction (skin thiickening at injection site)

Question 15

Ultra rapid acting insulin

Answer 15

Afrezza
Inhaled
12-15mins
Not for asthmatics, COPD

Question 16

What is the current approach for taking insulin?

Answer 16

Take one long acting, take rapid acting insulin with meals

Question 17

Oral hypoglycemic agents classes (6)

Answer 17

Sulfonylureas, biguanides, thiazolidinediones, acarbose, linogliride, incretins

Question 18

Sulfonylureas drugs, MOA, SE

Answer 18

Inactive K+ channel –> depolarize cell –> Ca+2 comes into cell –> secretion of insulin

Drugs: -amides (1st gen), -ides (2nd gen)
Tolbutamide, tolazamide, acetohexamide, chlorpropamide; Glipizide, glyboride

SE: Hypoglycemia, Transiet leukopenia; GI, allergies, derm probs

Question 19

Chlorpropamide is what kind of oral hypoglycemic agent? Who do we not give this to and why?

Answer 19

Sulfonylureas

Do not give to alcoholics b/c of disulfiram reactions - makes them very ill

Question 20

What is the drug for biguanides? MOA, effects, and SE

Answer 20

METFORMIN (Most common hypoglyemic agent)
Dec hepatic glucose production (stimulate glycolysis, slow glucose absorption from GI, inc insulin binding to R)
Does not cause hypoglycemia!!
Dec. hyperlipidemia (lower LDL, VLDL, cholesterol)
SE: Metallic taste, impaired B12 absorption leading to pernicious anemia

Question 21

What drug causes pernicious anemia? Why?

Answer 21

Metformin

Impairs B12 absorption

Question 22

What do thiazolidineiones (TZD) do? Name the drugs

Answer 22

(-zones)
Pioglitazone, rosiglitzone - improve ability to utilize insulin (Improve insulin sensitivity)
Dec. insulin R in periphery, agonist at PPARg –> transcription of insulin responsive genes

Question 23

Acarbose MOA, SE

Answer 23

Inhibit digestion of complex carbs –> excretion

SE: loose stool, diarrhea

Question 24

Linogliride

Answer 24

Insulin secretogogue

Even though it’s an -ide, it’s not a sulfonylurea

Question 25

Incretins

Answer 25

GI Hormones: GIP, GLP-1
Inc. insulin secretion, Dec. Glucagon, Dec. food intake

-ides: Exenatide, liraglutide

Inactivated by DPP4 enzyme; inhibit this to increase incretins