DM Drugs


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DM Drugs

  1. 1. Drugs forDiabetesMellitus<br />Internal Medicine<br />2010<br />
  2. 2. Islets of Langerhans<br /><ul><li>cells – glucagon
  3. 3. cells – insulin
  4. 4. cells – Somatostatin</li></ul>PP cells – pancreatic polypeptide<br />
  5. 5. Drugs used in Diabetes Mellitus<br />Insulin<br />per orem<br />Rapid Short-Acting<br />Insulin Secretagogue<br />Biguanides<br />Intermediate Acting<br />Insulin Synthesizer<br />Slow, long acting<br /> Glucosidase inhibitor<br />
  6. 6. Insulin<br />duplicate normal physiologic secretion of insulin<br />type 2 DM<br />use during times of illness or stress to maintain glycemic control<br />patients who are unable to maintain adequate control<br />exact time course of each insulin will depend on each particular preparation and site of injection<br />
  7. 7. Effects of Insulin<br />Liver<br />Increases storage of glucose as glycogen in liver<br />Decrease protein catabolism<br />Muscle<br />Stimulates glycogen synthesis and protein synthesis<br />Adipose Tissue<br />Facilitates triglyceride storage by: <br />activating plasma lipoprotein lipase<br />Increasing glucose transport into cells via GLUT 4 transporters<br />Reducing intracellular lipolysis<br />
  8. 8. Normal Plasma Glucose and Insulin Profile<br />
  9. 9. Human Insulin<br />1982: "recombinant DNA" into lab-cultivated bacteria or yeast<br />very short half life <br />insulin preparations are formulated to release insulin slowly into circulation<br />recombinant human insulin has replaced animal-derived insulin, such as pork and beef insulin<br />insulin analogs<br />structure differs slightly from human insulin to change onset and peak of action<br />
  10. 10. Insulin and Insulin Analogs<br />
  11. 11. Short and Rapid-Acting Insulin<br />act as mealtime insulin<br />administer before meals to mimic physiologic increases of insulin which occurs after meals<br />ASPART, GLULISINE, LISPRO<br />more rapid onset of action and shorter duration of action than regular insulin<br />premeal control before the next meal may be difficult due to short duration of action if used alone<br />
  12. 12. Crystalline zinc (Regular) Insulin<br />as a mealtime insulin, its use may be limited because onset is not so rapid to meet the quick, unpredictable increase in postprandial blood glucose<br />considered basal insulin<br />can be given IV or SQ<br />given 30 to 45 minutes ac<br />
  13. 13. Intermediate and Long-Acting Insulins<br />given SQ only<br />intend to mimic normal physiologic basal insulin secretion<br />usually given 1-2 times/day<br />LENTE<br />Intermediate-Acting Insuline<br />ULTRALENTE, DETEMIR, GLARGINE<br />Basal/ Long-Acting Insulins<br />
  14. 14. Combinations<br />short- and long-acting combinations are available commercially or may be combined in a single syringe by the patient<br />30% R/ 70% NPH<br />50/50<br />20/80<br />
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  19. 19. Different Insulin Regimen<br />2 daily injections<br />Multiple Daily Insulin Injection<br />Continuous Subcutaneous Insulin Infusion<br />Adverse Reactions<br />Hypersensitivity reactions<br />Hypoglycemia<br />Lipoatrophy or lipohyperthrophy<br />
  20. 20. Oral Antidiabetic Agents<br />sensitizers<br />Biguanides: Metformin<br />TZDs (PPAR): Pioglitazone, Rivoglitazone, Rosiglitazone<br />Dual PPAR agonist: Muraglitazar<br />
  21. 21. Oral Antidiabetic Agents<br />secretagogues<br />K+ ATP<br />sulfonylureas<br />1st gen: Gliclazide<br />2nd gen: Glibenclamide, Glipizide<br />3rd gen: Glimepiride<br />meglitinides: nateglinide, repaglinide<br />GLP-1 analogs: exenatide<br />DPP-4 inhibitors: saxagliptin, sitaglipitin<br />
  22. 22. Oral Antidiabetic Agents<br />α –glucosidase inhibitors<br />acarbose, voglibose, miglitol<br />amylin<br />pramlintide<br />SLGT2 inhibitors<br />dapaglifozine<br />others<br />benfluorex, tolrestat<br />
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  24. 24. Sulfonylureas<br />Mechanism of Action<br />Stimulate insulin release from pancreatic β cells<br />Decrease hepatic clearance of insulin<br />Primarily act by binding to the SUR subunit of the ATP-sensitive potassium (KATP) channel and inducing channel closure<br />
  25. 25. Sulfonylureas<br />Absorption, Fate, and Excretion<br />absorbed from git<br />decreased absorption with food and hyperglycemia<br />90 to 99% protein bound in plasma<br />metabolize in liver<br />metabolites excreted in kidney<br />2nd gen half life<br />short (3 to 5h)<br />long duration of action (12 to 24h)<br />
  26. 26. Sulfonylureas<br />1st GENERATION<br />Chlorpropamide/ Tolazamide/ Tolbutamide: once daily dosing, administer with breakfast<br />2nd GENERATION<br />Glibenclamide/ Gliclazide/ Glimepiride: once daily, administer with breakfast<br />Glipizide: 15-30 min before breakfast<br />
  27. 27. Sulfonylureas<br />Adverse Reactions: hypoglycemia, allergic reactions. GI upset<br />use with caution in patients with hepatic or renal failure<br />should not be used in DKA, major surgery, severe infections. stress or trauma, sulfa allergy<br />disulfiram reaction may occur with chlorpropamide and alcohol<br />
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  29. 29. Meglitinides<br />REPAGLINIDE<br />initial dose: 0.5 mg PO prior to meals; max: 16mg/day<br />MOA: derivative of benzoic acid; stimulate insulin release by closing ATP-dependent K channels in pancreatic β cells<br />absorbed rapidly from GIT; peak blood levels within 1 hour<br />Metabolize<br />90% in liver<br />10% in kidney<br />
  30. 30. Meglitinides<br />NATEGLINIDE<br />120mg PO 1-30min prior to main meals<br />MOA: from D-phenylalanine; stimulate insulin release by closing ATP-dependent K channels in pancreatic β cells<br />Reduce postprandial hypoglycemia<br />Metabolize:<br />84% IN LIVER<br />16% IN KIDNEY<br />
  31. 31. Biguanides<br />METFORMIN<br />absorbed mainly in small intestine<br />stable but does not bind with protein<br />excreted unchanged in urine<br />half life – 2 hours<br />MOA:<br />decrease hepatic glucose production -  gluconeogenesis<br />increase insulin action in muscle and fat<br />
  32. 32. Biguanides<br />METFORMIN<br />CONTRAINDICATIONS: renal impairment, hepatic disease, past history of lactic acidosis, cardiac failure, chronic hypoxic lung disease<br />Withheld for 48 hours after giving contrast media – to insure N kidney<br />ADVERSE REACTIONS: lactic acidosis, diarrhea, GI discomfort, nausea, metallic taste, anorexia<br />uptitrate slowly<br />
  33. 33. Thiazolidinediones (TZDs)<br />selective agonist for nuclear peroxisomeproliferator-activated receptor-gamma (PPAR)<br />requires insulin<br /> insulin resistance in peripheral tissue<br />
  34. 34. Thiazolidinediones (TZDs)<br />ROSIGLITAZONE AND PIOGLITAZONE<br />OD dose<br />Absorbed within 2 hours<br />Max effect observed in 6 to 12 weeks<br />Metabolized in Liver<br />Cytochrome P450 enzymes<br />Monitor liver enzymes regularly<br />May be given to patients with renal insufficiency<br />AE: anemia, weight gain, edema<br />C/I: Heart Failure<br />
  35. 35.  Glucosidase Inhibitor<br /> GI absorption of starch, dextrin, disaccharide by inhibiting the action of intestinal brush border ( glucosidase)<br />slow carbohydrate absorption<br />
  36. 36. Thank you!!!<br />