1. DH206: Pharmacology Chapter 21: Diabetes Mellitus Lisa Mayo, RDH, BSDH

2. Pancreatic Hormones

3. Islets of Langerhans 1.Alpha cells: secrete glucagon 2.Beta cells: secrete insulin

4. Diabetes Mellitus ▫Read p.233-237 for review of Type I & Type II diabetes if needed Pancreatic Hormones

5. Diabetes Mellitus ▫Drugs used to manage: presented differently than book 1.Insulin 2.Sulfonylureas 3.DPP-4 Inhibitors 4.Meglitinides 5.Biguanides 6.Alpha-Glucosidase Inhibitors 7.Thiazolidinediones 8.Combination drugs 9.Parental Adjuncts Pancreatic Hormones Need to know drugs in ppt in ea category! Drugs work on pancreas

6. 1.Insulin o Sub-Q o Used for Type I, some Type II o Drugs vary in onset action & duration o Adverse effect = Hypoglycemia Pancreatic Hormones ONSET & DURATION DRUG Short-ActingInsulin apart(Novolog) Insulin lispro(Humalog) Intermediate-ActingInsulin NPH(Humulin, Novolin) Long-ActingInsulin detemir(Levemir) Insulin glargine(Lantus) BOOK CORRECTION ON MED LIST & ONSET/DURATION USE THIS LIST, NOT BOOK

7. Pancreatic Hormones 1.Insulin  Indicated for Type I & II (when cannot be controlled by other means)  Administration o Subcutaneous injection o IV/IM for medical emergencies (ketoacidosis, diabetic coma) o NOT given orally  Insulin’s differ in onset and duration of action but have similar metabolic effects p.237

8. Injectable Insulin receptor is target tissue

12. Pancreatic Hormones 1.Insulin Adverse Reactions 1)Hypoglycemia is the most common adverse reaction to insulin (Administer glucagon: cake frosting) 2)Lipodystrophy at site of injection: disappearance of subcutaneous fat at site of injection

13. Diabetes Mellitus ▫Drugs used to manage: presented differently than book 1.Insulin 2.Sulfonylureas 3.DPP-4 Inhibitors 4.Meglitinides 5.Biguanides 6.Alpha-Glucosidase Inhibitors 7.Thiazolidinediones 8.Combination drugs 9.Parental Adjuncts Pancreatic Hormones Drugs work on pancreas Side Effects: Weight gain Hypoglycemia

14. 2.Sulfonylureas / Secretagogue o First oral agents used in diabetes management o 1 st & 2 nd generation drugs (2 nd most common = less side effects, more potent so smaller doses used and less toxicity chance) o Mechanism of action  Stimulate release insulin from beta cell of pancreas (see next slide) Pancreatic Hormones Sulfonylureas/Secretalgogues Glimepiride(Amaryl) Glipizide(Glucotrol) Glyburide(DiaBeta, Glynase) p.238

15. ↑ Insulin secretion Sulfonylureas

16. 3.DPP-4 Inhibitors Physiology Review ▫Incretin GLP-1 (gut hormone that is glucose- dependent) ↓ ▫Cause release of insulin in response to glucose in the gut (diabetics have less secretion of GLP-1) ▫Drugs in this category inhibit DPP-4 so GLP-1 has more time to stimulate insulin secretion ▫Remember: insulin moves glucose out of the blood Pancreatic Hormones p.240 DPP-4 INHIBITOR Sitagliptin(Januvia) DPP-4 breaks down GLP-1

17. DPP-4 Inhibitors ↑ Insulin secretion

18. 4.Meglitinides  Newest class of oral drugs  Increase insulin secretion from pancreas but at a different site than sulfonylureas drugs  Taken before meals – miss meal do NOT take drug  Weight gain, hypoglycemia common Pancreatic Hormones Meglitinides Repaglinide(Prandin) nateglinide(Starlix) p.238

19. Meglitinides ↑ Insulin secretion Different receptors on pancreas than sulfonylureas

20. Diabetes Mellitus ▫Drugs used to manage 1.Insulin 2.Sulfonylureas 3.DPP-4 Inhibitors 4.Meglitinides 5.Biguanides 6.Alpha-Glucosidase Inhibitors 7.Thiazolidinediones 8.Combination drugs 9.Parental Adjuncts Pancreatic Hormones Side Effects: LDL chol. Cardiac Respiratory Renal NO weight gain or hypoglycemia

21. 5.Biguanides  Action Decrease glucose production Stimulate glucose uptake into tissues  No weight gain, hypoglycemia like sulfonylureas & meglitinides DOES NOT affect insulin production/secretion – why does not cause hypoglycemia or weight gain Pancreatic Hormones Biguanides Metformin(Glucophage) p.238

23. Diabetes Mellitus ▫Drugs used to manage: presented differently than book 1.Insulin 2.Sulfonylureas 3.DPP-4 Inhibitors 4.Meglitinides 5.Biguanides 6.Alpha-Glucosidase Inhibitors 7.Thiazolidinediones 8.Combination drugs 9.Parents Adjuncts Pancreatic Hormones NO weight gain, hypoglycemia Side Effect: GI

24. 6.α -Glucosidase Inhibitors ACTION Interfere with CHO digestion through enzyme blocking in stomach ↓ Delays glucose absorption ↓ Prevents blood glucose levels after meals (postprandial) from immediately peaking Pancreatic Hormones α -Glucosidase Inhibitors Acrabose(Precose) Miglitol(Glyset) p.240

25. Stomach α -Glucosidase Inhibitors

26. Diabetes Mellitus ▫Drugs used to manage: presented differently than book 1.Insulin 2.Sulfonylureas 3.DPP-4 Inhibitors 4.Meglitinides 5.Biguanides 6.Alpha-Glucosidase Inhibitors 7.Thiazolidinediones 8.Combination drugs 9.Parental Adjuncts Pancreatic Hormones Side Effects: Weight gain Fluid retention Liver damage Thiazolidinediones & Combo missing from your text Very important drugs in diabetes management – in board books

27. 6.Thiazolidinedione's ▫Newer drugs, 2 nd line therapy, usually used in combo with other drugs ▫Referred to as “insulin sensitizers” ▫Action  Enhance insulin response in fat & liver cells = glucose utilized more efficiently  Causes the removal of glucose from blood into cells Pancreatic Hormones Thiazolidinediones Rosaglitazone(Avandia) Prolitazone(Actos)

28. Thiazolidinediones (fat & liver) “Insulin sensitizer”

29. Diabetes Mellitus ▫Drugs used to manage: presented differently than book 1.Insulin 2.Sulfonylureas 3.DPP-4 Inhibitors 4.Meglitinides 5.Biguanides 6.Alpha-Glucosidase Inhibitors 7.Thiazolidinediones 8.Combination drugs 9.Parental Adjuncts Pancreatic Hormones Thiazolidinediones & Combo missing from your text Very important drugs in diabetes management – in board books

30. 8.Combination drugs Pancreatic Hormones Combination Drugs: Metformin + Classification Glipizide(Metagrip)Sulfonylureas Glyburide(Glucovance)Sulfonylureas Rosiglitazone(Avandamet)Thiazolidinedione

31. Diabetes Mellitus ▫Drugs used to manage: presented differently than book 1.Insulin 2.Sulfonylureas 3.DPP-4 Inhibitors 4.Meglitinides 5.Biguanides 6.Alpha-Glucosidase Inhibitors 7.Thiazolidinediones 8.Combination drugs 9.Parental Adjuncts Pancreatic Hormones

32. DRUGNOTATIONS Exenatide(Byretta)Injectable non-insulin GLP-1 agonist Pramlintide(Symlin)Injectable non-insulin used at mealtimes Amylin Analog (amylin slows gastric emptying & is deficient in diabetics) Helps increase satiety MANY BLACK BOX WARNINGS p.240 9. Parental Adjuncts: not to be used as stand-alone tx These agents are NOT in Mosby’s DH Board Review Book