Drugs for Diabetes

Katzung, Chapter 41; 723-745

After reading the chapter and attending the lectures, you should be able to answer the following:

REVIEW QUESTIONS FOR DIABETES LECTURES

1. What are the differences between Type 1 and Type 2 diabetes mellitus? What are some of the complications of diabetes mellitus? What are pancreatic islets? What types of islet cells make insulin? Islet amyloid polypeptide (IAPP)? Glucagon? Note: Be very comfortable with the slide dealing with glucose homeostasis and the effects of insulin.

2. What is preproinsulin? Proinsulin? Insulin?

3. Describe the Insulin receptor and its signaling pathways… in your answer make sure to use terms such as, “signal transduction,” “phosphorylation,” “tyrosine kinase,” “IRS-1,” “Shc,” “GLUT4” etc…

4. What is ketoacidosis? Can you smell acetone on the breath of severe Type 1 diabetics? Good video describing this at: https://www.youtube.com/watch?v=jYF0Y0uBgVo I watched the video. It is accurate.

5. Describe glucose uptake into cells. Describe all GLUT transporters and comments as to where they are in the body

6. Understand the role of glucose uptake through GLUT2 in beta cells and how that affects the ATP-gated K+ channel and insulin release.

7. What happens to GLUT4 transporters when insulin levels rise? Where are they normally… where do they go? What happens to these transporters when insulin levels in blood decrease? Do GLUT4 transporters stay in the cell membrane? or do they return home.. back to the cytoplasm where they are contained in vesicles?

8. What are some of the metabolic effects of insulin on the liver? On the skeletal muscle? On fat cells?

9. What are the four major types of insulin preparations available? Is insulin administered orally? Why not? Does it have a long half-life? Which of the insulins are slowly absorbed and why?

10. Using these terms…. Hexamers… dimers… monomers…. Two amino acid change.. insulin…. Lispro…decreased hydrogen binding of insulin with itself… Explain to your study partner or a complete stranger who is willing to listen why insulin lispro, insulin aspart and insulin glulisine are rapid acting.

11. What effect(s) are caused as the result of having zinc and acetate in an insulin preparation?

12. Protamine can be combined with regular insulin to produce intermediate-acting insulin preparations. WHY does that work in slowing down absorption of regular insulin?

13. Please be very familiar with the tables listing the different types of insulin preparations. Focus on the type.. the time to peak effect.. and the duration of action.

14. Is hypoglycemia the most common side effect of insulin therapy? Are all type 1 diabetics treated with insulin replacement? Is type 1 the result of beta pancreatic cell destruction?

15. What are the clinical indications for pramlintide? What are its chief pharmacological actions? What are its most relevant ADME parameters? Is there a boxed warning associated with this drug? What’s that all about?

16. Would you use sulfonylureas in Type 1 or Type 2 patients?? Think about the role of the beta cell in the action of these drugs.

17. Where do the sulfonylureas act? (inhibit the ATP-dependent K+ channel of beta cells). Be able to identify sulfonylureas such as first generation and second generation: NOTE: These drugs can induce hypoglycemia…..nausea, diarrhea & vomiting.

The following link is interesting: http://www.mja.com.au/public/issues/180_02_190104/vei10508_fm.html
It provides some case studies and things to think about in patients using sulfonylureas.
Please read the article. It’s not required… but suggested.

18. Meglitinides cause insulin release from beta cells. Two major meglitinides- repaglinide & nateglinide. How do they work? adverse effects? Receptor binding sites? Which seems to be more efficacious in people and what is your decision based on?

19. What is lactic acidosis and is it related to metformin use, especially in patients with liver disease, renal impairment and cardiopulmonary insufficiency? Know the MOA of metformin and common adverse effects. Is B12 absorption affected?

20. Understand the relationship of rosiglitazone and the receptor for PPARgamma (peroxisome proliferator activated receptor- gamma). What are the shared adverse effects of rosiglitazone and pioglitazine? Increased risk of which cancer has been associated with pioglitazone? (Treating Type 2 Diabetes With Pioglitazone May Increase Risk of……. Go to: http://www.aafp.org/online/en/home/publications/news/news-now/health-of-the-public/20120611pioglitazone.html#.UFvpQz4HUsg.twitter … —which ends up to be something like an extra 16.9 cases per 100,000 person years.

21. How may chromium be related to diabetes? What affect does chromium deficiency have on the body?

22. Alpha-glucosidase inhibitors. HOW DO THEY WORK? Chief adverse effects? Any contraindications for this class of drugs?

23. Glucagon is the physiological antagonist to insulin made by alpha cells of the pancreatic islet. Is glucagon often elevated in patients with Type 2 diabetes? If so, why?

24. How does exenatide work? Adverse effects? Receptor binding sites? Compare and contrast exenatide with liraglutide.

25. Incretin mimetics. Adverse effects? Mechanism of action?


26. DPP-IV inhibitors. Adverse effects? Mechanism of action?

27. Describe the pharmacology of sodium glucose co-transporter 2 inhibitors in terms of mechanism of actions and adverse effects. How do these drugs differ in terms of anticipated adverse effects compared to sulfonylureas?

28. What does the following website have to say about dapagliflozin and its approval status by the FDA? http://www.drugs.com/newdrugs/fda-approves-farxiga-type-2-diabetes-4002.html