Drugs for Diabetes Mellitus 1

Question 1

Insulin preparations - MoA

Answer 1

Binds to insulin receptors (mainly skeletal muscles, liver and adipose tissue) activating tyrosine kinase –> phosphorylation of insulin receptor substrate proteins (ISP). Alters enzymes for metabolism. Also increased glucose transporter molecules in membranes (GLUT4) (muscle & fat tissue)

Question 2

Insulin preparations - Clinical use

Answer 2

Used for ALL patients with DM1, and 1/3 of DM2

Gestational diabetes

Question 3

Insulin preparations - Administration

Answer 3

Adm subcut (injection or infusion), inhalation

Question 4

Insulin preparations - Adverse effects

Answer 4

Lipodystrophy at injection site

Question 5

Rapid-acting insulin - Clinical use

Answer 5

Postprandial glycemia

Question 6

Rapid-acting insulin - Special considerations

Answer 6

Onset: 10-20 min, peak at 1h. Duration: <3h

Question 7

Rapid-acting insulins/ human insulin analogues

Answer 7

Insulin lispro
Insulin aspart
Insulin glulisine

Question 8

Short-acting insulin

Answer 8

Regular insulin

Question 9

Regular insulin - MoA

Answer 9

Consists of insulin hexamers crystallized around a zinc molecule.

Question 10

Regular insulin - Clinical use

Answer 10

Diabetic ketoacidosis (IV)

Question 11

Regular insulin - Special considerations

Answer 11

Onset: 30-60 min after injection.
Duration: 5-8h
NOT suitable for postprandial glycemia.

Question 12

Intermediate-acting insulin

Answer 12

Isophane insulin aka neutral protamine Hagedorn (NPH)

Question 13

Isophane insulin aka neutral protamine Hagedorn (NPH) - MoA

Answer 13

Consists of particles of insulin combined with zinc and protamine

Question 14

Isophane insulin aka neutral protamine Hagedorn (NPH) - Clinical use

Answer 14

DM2

Question 15

Isophane insulin aka neutral protamine Hagedorn (NPH) - Special considerations

Answer 15

More prone to erratic absorption and intrapatient variations than long-acting insulins
Low-cost alternative

Question 16

Long-acting insulins

Answer 16

Insulin glargine
Insulin detemir
Insulin degludec

Question 17

Long-acting insulin - MoA

Answer 17

Provide basal levels of insulin and facilitate control of glycemia throughout the day.

Question 18

Long-acting insulin - Special considerations

Answer 18

Slow release of insulin – basal level

Diabetic pt started on lower dose.

Question 19

Insulin glargine - MoA

Answer 19

Amino acid substitutions in the A and B chains –> released slowly

Question 20

Insulin glargine - Clinical use

Answer 20

DM1 & DM2

Question 21

Insulin glargine - Special considerations

Answer 21

No peak effect. Often in combo with rapid-acting insulin

Adm 1-2 x daily

Question 22

Insulin detemir - MoA

Answer 22

Reversibly binds to albumin in ECF & plasma

Question 23

Ultralong-acting insuilin

Answer 23

Insulin degludec

Question 24

Inhaled insulin - Clinical use

Answer 24

Postprandial glycemia DM1

Question 25

Inhaled insulin - Special considerations

Answer 25

Alternative to short- or rapid-acting insulin esp if injection site reactions, needle aversion, difficulty injecting.
Also effective when injected

Question 26

Hypoglycemic drugs - MoA and Clinical use

Answer 26

Increases insulin secretion

DM2

Question 27

Hypoglycemic drugs - groups

Answer 27

Sulfonylurea drugs and Meglitinide drugs

Question 28

Sulfonylurea drugs - MoA

Answer 28

1) Inh ATP-sensitive potassium channels, preventing K+-efflux and causing Ca2+-influx and activation of pulsatile insulin secretion. No effect on basal insulin secretion.
2) Decreasing glucagon secretion by increasing insulin and increasing pancreatic somatostatin secretion.
3) Increase insulin sensitivity in DM2

Question 29

Sulfonylurea drugs - Clinical use

Answer 29

DM2 (without other drugs or dietary restrictions, exercise, weight reduction).
Combo therapy with metformin

Question 30

Sulfonylurea drugs - Special considerations

Answer 30

1st generation of these drugs are no longer used!
Advise pt to limit alcohol to 60 ml daily.
Therapy starts with low doses

Adm orally

Question 31

Sulfonylurea drugs - Adverse effects

Answer 31

Weight gain
Hypoglycemia (skipped meals, inadequate carbohydrate intake, excessive doses, renal/hepatic diseases), skin rashes,
nausea, vomiting,
cholestasis,
hematologic reactions (leukopenia, thrombocytopenia, hemolytic anemia)

Question 32

Sulfonylurea drugs - Interactions

Answer 32

Decreased effectiveness when given with: Thiazide diuretics, corticosteroids, estrogens, thyroid hormones, and phenytoin

Increases hypoglycemic effect when given with:
Angiotensin-converting enzyme inhibitors, sulfonamides, salicylates, NSAIDs, gemfibrozil, alcohol

Alcohol: disulfiram-like reaction

Question 33

Sulfonylurea drugs

Answer 33

Tolbutamide - not used
Glimepiride
Glipizide
Glyburide (glibenclamide)

Question 34

Glipizide - Special considerations

Answer 34

Absorption is decreased by food. Given 30 min before breakfast.

Question 35

Meglitinide drugs

Answer 35

Repaglinide

Nateglinide

Question 36

Meglitinide drugs - MoA

Answer 36

Inh ATP-sensitive potassium channels, preventing K+-efflux and causing Ca2+-influx and activation of pulsatile insulin secretion. No effect on basal insulin secretion.

Question 37

Meglitinide drugs - Clinical use

Answer 37

Postprandial glycemia (short duration of action)
DM2 (1st line)
Comb with metformin

Question 38

Meglitinide drugs - Special considerations

Answer 38

Should not be used with other oral antidiabetic drugs or insulin. Can be used with metformin.
Taken before meals

Question 39

Meglitinide drugs - Adverse effects

Answer 39

Hypoglycemia

Question 40

Contraindication for DIA 1 patients

Answer 40

Beta blockers: mask hypoglycemic symptoms