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  1. Type 1 diabetes mellitus etiology
    Genetic, Autoimmune destruction of pancreatic beta cells that produce insulin
  2. Type 2 diabetes mellitus etiology
    Genetic, Metabolic abnormalities, environmental factors
  3. Type 1 diabetes onset
    childhood or early childhood before puberty
  4. Type 2 diabetes onset
    any age, usually after age 35
  5. Type 1 diabetes treatment (general)
    insulin, +/- thiazolidine dione
  6. Type 2 diabetes treatment (general categories)
    • 1. oral hypoglycemic agents
    • 2.Antihyperglycemic agents
  7. Agents that promote Insulin Release
    sulfonylurea, meglitinide, Incretin Analogues, DPP-IV inhibitors
  8. Types of Antihyperglycemic agents
    metformin, thiazolidinediones, alpha glucosidase inhibitors
  9. Actions of Insulin
    Carbohydrate metabolism, lipid metabolism, protein metabolism
  10. Adverse effects of insulin
    hypoglycemia, visual disturbances, peripheral edema, local or systemic allergic reactions
  11. Sulfonylurea action
    Promote insulin release by binding to and inhibiting K+ conductance by Kir6.2
  12. Adverse effects of sulfonylureas
    hypoglycemia, gastrointestinal disterbances, hematological disturbances, ethanol intolerance, Contraindicated in patients with hepatic renal insufficiency
  13. Meglitinide actions
    Inhibit K+ conductance by Kir 6.2 ----> result in membrane depolarization and insulin release
  14. Incretin Analog actions and route of administration
    • Increase glucose uptake results in closure of the Kir6.2
    • (mostly used as adjunct therapy)
    • SC injection
  15. Dipeptidyl Peptidase - IV inhibitor actions
    Decreases the inactivation of endogenous incretin hormones ----> Results in a glucose - dependent increase of insulin release and decrease in glucagon levels (used in adjunct therapy)
  16. Pharmacokinetic issues of Agents that promote insulin release
    • Mostly oral administration
    • Highly protein bound
  17. General function of anti hyperglycemic Agents
    Lower elevated levels of blood glucose with relatively little potential to produce hypoglycemia. They do not promote insulin release
  18. Types of Antihyperglycemic Agents
    Biguanides, Thiazolidinedione, alpha-Glucosidase inhibitor, Modified amyline peptide
  19. Biguanides (metformin) function
    • decreases the hepatic glucose output
    • Inhibits absorption of glucose from the gut
    • Increases glucose uptake by muscle and fat cells
    • Its mechanism of action appear to involve activation of cAMP dependent protein kinase
    • Activation of this kinase in skeletal muscle and adipocytes leads to increase glucose transport by promoting translocation of GLUT4 to the cell surface
  20. Adverse Effect of metformin
    Lactic acidosis and gastrointestinal problems
  21. Thiazolidinediones action
    increases insulin sensitivity by binding ligand activated transcription factor PPAR - y which then activates PPAR - y and increases the expression of mRNAs encoding enzymes and proteins required for optimal insulin sensitivity
  22. Thiazolidinediones adverse effects
    weight gain, edema, possible hepatic toxicity, cardiovascular side effects
  23. Alpha glucosidase inhibitors
    Inhibit alpha - glucosidases, enzymes in the GI tract involved in degradation of complex carbohydrates which stall the rise in blood glucose concentrations after a meal (does not enter the blood stream)
  24. Adverse effects of alpha glucosidase inhibitors
    • abdominal pain
    • diarrhea
    • flatulence
  25. Amylin Analog action and route of administration
    • acts like insulin to inhibit glucagon secretion
    • It also delays gastric emptying
    • It also has appetite suppressive properties
    • SC administration
  26. PK issues for anti hyperglycemic agents
    • Mostly oral
    • TZD are highly protein bound
  27. Dapagliflozin action
    inhibits sodium glucose cotransporter 2 and block resorption of glucose in the kidney, leading to an increase in urinary glucose excretion and lowering of both plasma glucose levels and body weight
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2014-03-03 23:12:17

chapter 43
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