Diabetes

Question 1

What are the 2 traditional insulin preparations?

Answer 1

Regular insulin and Isophane insulin

Question 2

PK of regular insulin (onset, duration, prep, admin)

Answer 2

Rapid onset.
Short acting - good mealtime insulin
Prepared with zinc to be readily soluble and absorbed.
Can be given IV

Question 3

PK of Isophane insulin (NPH)

Onset, duration, prep, admin

Answer 3

Slower than RI
Longer action than RI - baseline insulin (not mealtime insulin)
Insulin complex with protein protamine at neutral pH
Cloudy suspension - not to be given IV

Question 4

When should regular insulin be administered?

Answer 4

Injected prior to meal (~30min)

Question 5

Use of Isophane insulin and regular insulin

Answer 5

Usually taken in combination with regular insulin, to maintain a baseline levels of insulin.
Dosing regimens would depend on patient needs.

Question 6

What are the rapid and short biosynthetic insulin analogs?

Answer 6

Insulin lispro, insulin aspart, Insulin glulisine

Question 7

What are the slow and long biosynthetic insulins?

Answer 7

Insulin glargine

Insulin detemir

Question 8

Properties of Insulin lispro

Answer 8

Injected immediately before meals.
Levels available immediately, and insulin levels fall rapidly to decrease risk of post-prandial hypoglycemia.
All rapid insulins approved for IV use.

Question 9

Properties of Insulin aspart

Answer 9

Same as lispro

Question 10

Properties of Insulin glulisine

Answer 10

Same as aspart and lispro. Can be injected immediately before or after meals.

Question 11

Uses for the Isophane formulations of rapid insulin analogs?

Answer 11

Formulated to slow their action and longer duration for between-meal effects.

Question 12

Properties of insulin glargine

Answer 12

Formulated with zinc

Very slowly absorbed, for long, low, constant action.

Question 13

Properties of insulin detemir

Answer 13

Myristic acid attached, binds to albumin, prolongs action.
Better and less variable absorption than glargine.
Somewhat shorter action than glargine.

Question 14

How to use the long and short acting insulins?

Answer 14

Do not mix in syringe (will affect rapid insulins).

Both given at bedtime.

Rapid and ultra-long insulins usually used in combination.
“Basal plus bolus”

Lispro/aspart/gluisine>regular>isophane (and NP analogs)>glargine/detemir

Question 15

How do all of the insulins compare in terms of efficacy?

Answer 15

All are equally efficacious, pure insulin agonists.

Question 16

Uses/MOA/administrations of Glucagon

Answer 16

Acts to increase blood glucose in cases of hypoglycemia. Can be administered IV, IM, or inhalation.

Question 17

Properties of Pramlintide

Answer 17

Decreases post-prandial glucose therefore decreases short-acting insulin needs. Also inhibits glucagon.

Question 18

Uses of Pramlintide

Answer 18

Used to Type I and II already on insulin but not controlled by insulin alone.
Basal + bolus + pramlintide

Question 19

Possible side effects of Pramlintide

Answer 19

Increased risk of hypoglycemia.
Avoid in patients with renal disease.
Lack of weight gain is a plus!

Question 20

Uses of oral anti-diabetic agents.

Answer 20

For patients who don’t need more insulin, just need it to be more efficacious.
Can be used with insulin treatment.
Used in Type II only.

Question 21

Mechanism of Sulfonylureas (Glimepiride)

Answer 21

Enhance secretion of insulin by beta cells by blocking ATP-sensitive K+ channel.
Decreased glucagon.
Increase cell sensitivity to insuiln.

Question 22

Contraindications of Glimepiride (sulfonylurea)

Answer 22

Patients with liver or kidney disease.

Question 23

Mechanisms of Meglitinides (Repaglinide)

Answer 23

Similar to SUs, just structurally different.

Faster than SUs, shorter duration.

Question 24

When to take Repaglinide

Answer 24

Taken 30 minutes before each meal.

Question 25

Mechansims of Biguanides (metformin)

Answer 25

Targets AMP kinase (liver enzyme)

Decreases glucose production, increases glucose uptake, increasing insulin effectiveness.

Question 26

Uses of metformin

Answer 26

Important drug for obese patients with insulin resistance.
Can be used with SUs (diff mech).
Can be used with insulin (makes insulin more effective).

Question 27

Contraindications of metformin

Answer 27

Patients with kidney disease.

Question 28

Side effects of metformin

Answer 28

No weight gain.
No hypoglycemia.
Inhibits lactate metabolism - could be serious even in mild renal disease.
Upset GI

Question 29

Mechanism and uses for Acarbose

Answer 29

“Distracts” enzymes in the gut, therefore decreases glucose uptake in gut.
Taken 30 min before meals.
Used in mild disease or in adjunct with other meds.

Question 30

Side effects of Acarbose.

Answer 30

No hypoglycemia on its own, but possible with other meds being taken.
Don’t take with metformin because also causes GI upset.

Question 31

Mechanism of Thiazolidinediones (Pioglitazone, Rosiglitazone)

Answer 31

Activates PPAR-gamma to enhance transcription of insulin genes (makes insulin work better)
Decreases gluconeogenesis
Increases glucose uptake (insulin sensitizer)
Decreases fatty acid production in adipocytes

Question 32

Can Thiazolidinediones (Pioglitazone, Rosiglitazone) be used in patients with renal disease?

Answer 32

Yes, they’re metabolized by the liver.

Question 33

Side effects of Thiazolidinediones (Pioglitazone, Rosiglitazone)

Answer 33

Heptotoxicity and fatal liver disease.
May increase bladder CA risk.
Can increase fracture risk (contraindicated in osteoporosis)

Question 34

Mechanisms and effects of Exenatide and Liraglutide

Answer 34

Analogs of GLP-1.
Potentiate insulin secretion, slow gastric emptying, and increase satiety.
Reduces fasting and post-prandial glucose levels.
Do not cause weight gain, can cause weight loss.

Question 35

Uses of Exenatide and Liraglutide

Answer 35

Can be used alone or with insulin or other oral agents.
Injected.
Liraglutide is approved for weight loss.

Question 36

Side effects of Exenatide and Liraglutide

Answer 36

Hypoglycemia risk.
Renal failure risk.
Possible thyroid tumors and pancreatitis.