REVIEW QUESTIONS FOR DIABETES LECTURES
1.
Required Reading: Katzung, 12th ed., Chapter Chapter 41, p. 743-768
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?
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…… —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. sodium glucose co-transporter 2 inhibitors. Canagliflozin. Adverse effects? Mechanism of action?
28. According to the information on the article published in the Lancet (Vol 382 September 14, 2013) and entitled, “SGLT2 inhibitors for diabetes: turning symptoms into therapy,” which was authored by Drs. Michaela Diamant and Linde M Morsink, why was Dapagliflozin not approved in the US by the FDA? What other SGLT2 inhibitors have passed through Clinical Trials and are now going through the approval process in various places, including Europe, the US and Japan?
REVIEW QUESTIONS FOR THYROID
Required Reading: Katzung, 12th ed., Chapter Chapter 38, p. 681-696
1. What is the chemical name for the three hormones secreted by the thyroid gland? Can you draw the structures of T3? T4? Where do the ‘iodides’ come from? Are they synthesized by the body? Are they derived from the diet? What is the RDA of iodide in the diet?
2. Describe the biosynthesis of thyroid hormones. Make sure to use terms like iodide trapping, thyroidal peroxidase, tyrosine, MIT, DIT, thyroglobulin, proteolysis of thyroglobulin. What is the ratio of T4 to T3 on thyroglobulin? Which of these is released to a higher degree from the thyroid gland? Which of the two is the more active hormone? How is T4 converted to T3 in the periphery?
3. What are the two chemical activities of thyroidal peroxidase? Compared to T4 and T3, what is the biological activity of rT3? What is the half life of T4? T3? Describe the possible metabolic fates of T4 after it is released from the thyroid gland. Describe the relationship among the thyroid gland, the hypothalamus, and the pituitary gland.
4. What are the relevant ADME pharmacokinetic parameters of T3 and T4? For example, which is better absorbed? Are there factors that can affect absorption? Which has the longer half-life?
5. What is the net effect of an ‘activating’ mutation of the TSH receptor? Provide an example of an abnormal thyroid stimulating agent.
6. What happens to T4 when it enters the cell? What is 5’deiodinase? What kind of receptors are thyroid hormone receptors? For example, are they transmembrane spanning receptors? What other types of receptors are related to thyroid receptors? Can T4 bind to T3 receptors?
7. What are the normal physiological effects of thyroid hormones? What happens to these effects in the hyperthyroid state? Remember to detail the effects of the hyperthyroid state on skin, eyes, cardiovascular system, respiratory, GI, CNS, musculoskeletal, renal, and hematopoietic systems as well as on metabolism. (See also Table 38-4 in your text for help).
8. What are ‘antithyroid agents?’ What are ‘goitrogens?’ How do the thioamides work to reduce the production of thyroid hormones by the thyroid gland? Can you describe three different thioamides that do this? Be sure to include relevant PK differences in your answer. Aside from inhibiting thyroidal peroxidase, what other enzyme is blocked by these agents (hint: it’s in the periphery). Discuss the pertinent pharmacokinetic properties of these thioamides. Do these agents have a fast or a slow onset of pharmacologic effect? What is the most common adverse reaction caused by these agents? What are some of the rare but serious adverse effects associated with these agents? Carbimazole is a prodrug? How does it work as an anti-thyroid agent? What are its most significant adverse effects? Based on its PK, would you recommend carbimazole over propylthiouracil in pregnancy? Why or why not?
9. What is Grave’s Disease? Is Grave’s Disease frequently associated with exophthalmus and swelling of the periorbital tissues?
10. What is ipodate? What is it’s mechanism of action? What are its most significant adverse effects?
11. What is the antithyroid mechanism of action of I-131 (radioactive iodine)? What is its half-life? Should it be used in pregnant patients? Why or why not?
12. What is the antithyroid mechanism of action of propranolol?
13. List three anion inhibitors of the Na+/I- transporter? Why do such agents have antithyroid activity?
14. How do iodides work to block thyroid function? What is the proposed mechanism of iodide’s antithyroid actions? Why might iodides be helpful in preoperative preparation for surgery?
15. How does guanethidine work as a potential anti-thyroid agent? Does it have direct effects on the thyroid gland?
16. What are some of the clinical manifestations of hypothyroidism? What is Hashimoto’s thyroiditis? What is ‘cretinism?’ What is ‘myxedema?’
17. Describe the types of synthetic and animal-derived thyroid hormones available for replacement therapy. What is the preparation of choice for thyroid replacement therapy?
18. How might drugs like lithium or amiodarone affect levels of T4 in the body (Hint: see Table 38-3).
19. What is ‘thyroid storm?’ What is the presenting syndrome? Which pharmacological agents can be used to treat thyroid storm? What is the rationale behind using each of those reagents?
20. Describe the functional domains of the thyroid hormone receptor? What is the mechanism of thyroid hormone action? Can genes be both activated or inhibited by thyroid hormone?
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