thera DM

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thera DM
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2013-10-30 00:48:58
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thera DM
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  1. metformin MOA
    • decrease hepatic glucose production
    • decrease intestinal glucose absorption
    • increase insulin actoin
  2. advantages of metformin
    • decrease A1c 1-1.5
    • weight loss or neutral
    • decrease cardiovascular events
    • increase insulin sensitivity in obese pts
    • low cost
  3. adverse effects of metformin
    • GI disturbances
    • metallic taste
    • B 12 deficiency
    • rash
    • lactic acidosis (rare)
  4. what is the root of lactic acidosis for metformin
    decreased glucose production -> increase pyruvate -> increased lactic acid
  5. CI/cautions for metformin
    • renal insufficiency
    •   scr > 1.5 male,  >1.4 female
    • severe hepatic insufficiency
    • severe/acute CHF
    • acute MI
    • radiographic dyes
  6. drug interactions for metformin
    • alcohol increases risk for lactic acidosis
    • cephalexin, cimetidine increase metformin levels
    • contrast dye increase toxic effects
  7. typical patient candidate for metformin
    • TIIDM with
    •   obesity and/or
    •   insulin resistance
    • "pre-diabetes"
    • PCOS
  8. Glucophage dosing
    • begin with 500 mg QD/BID
    • titrate to a max of 2550 mg/day
    • take with food
  9. glucovance dosing
    • starting does 1.25mg/250mg QD/BID
    • max dose 20mg/2000mg
  10. what is glucovance and its strengths
    • glyburide and metformin
    • 1.25/250 mg
    • 2.5/500 mg
    • 5/500 mg
  11. doses of metformin
    • 500
    • 850
    • 1000
  12. sulfonylureas MOA
    stimulate endogenous insulin release from pancreas
  13. advantages of sulfonylureas
    • decrease A1c 1-1.5
    • well tolerated
    • decrease CV events
    • low cost
  14. disadvantages of sulfonylureas
    • hypoglycemia
    •   vigorous exercise
    •   skip meals
    • weight gain
  15. avoid/caution for sulfonylureas
    • renal impairment
    • hepatic impairment
    • G6PD deficiency = anemia's
    • elderly
    • malnutritioned
  16. major adverse effect with sulfonylureas
    • anemias
    • hepatitis
    • jaundice
    • hyponatremia
  17. sulfonylureas drugs
    • glipizide - glucotrol
    • glimepride - amaryl
    • glyburide - diabeta, micronase, glynase (micronized)
  18. glipizide dosing
    • max 40 mg QD, XL 20mg/day
    • doses > 15 mg/day - divide them
    • give 30 minutes before meal
    • adjustments
    •   renal - CrCl < 50, decrease by 50%
    •   hepatic - start at 2.5 mg QD
  19. glyburide dosing
    • micronized (glyset)
    • hepatic - avoid in severe
    • renal - CrCl < 50 not recommended

    1.25 - 20 mg QD/BID
  20. glipizide strengths
    • regular - 5,10
    • XL - 2.5,5,10,20
  21. glyburide strengths
    • regular - 1.5,2.5,5
    • micronized - 1.5,3,6
  22. glimepride dosing
    • max 8mg/day
    • give w/first main meal
    • renal impairment - start 1 mg QD titrate & monitor
    • hepatic - same as renal
  23. meglinitides
    • repaglinide - prandin
    • nateglinide - starlix
  24. meglinitide MOA
    • increase insulin secretion (rapid) - glucose dependent
    • like a short acting sulfonylurea
  25. meglinitides advantages
    • decrease A1c .5-1
    • better postprandial glucose lowering - increased physiologic insulin release after a meal
    • but can lower fasting as well
  26. meglinitide disadvantages
    • hypoglycemia
    • weight gain
    • dosing frequency - TID/QID
  27. meglinitides CI's
    • hypersensitivity
    • children
    • pregnancy
  28. repaglinide (prandin) dosing
    • 4mg/meal or 16 mg/day
    • if meal is skipped, skip dose
    • renal - CrCl 20-40, start at 0.5 mg titrate carefully
    •           CrCl < 20 don't do
    • hepatic not defined
  29. nateglinide dosing
    • 120 mg TID
    • renal - no adjustments
    • hepatic - mod-severe impairment, caution advised
  30. meglinitides adverse effects
    • HA
    • upper respiratory tract infections
    • hypoglycemia, but less than OSA
    • cardiovascular, but less than metformin
  31. meglinitide considerations
    • role in therapy - post-prandial hyperglycemia
    • poor response if same for OSAs
    • don't combine with OSAs
    • give 0-30 minutes before meal
    • cost medium
  32. thieazolidinediones (glitazones)
    • actos - pioglitazone
    • Avandia - rosiglitazone
  33. TZD MOA
    • PPAR-y
    • increases peripheral insulin sensitivity
    • decreased hepatic glucose production
  34. adverse effects of TZD's
    • edema
    • wt gain
    • bone fractures
    • bladder cancer
    • HF risks
  35. TZD renal & hepatic considerations
    • renal - none
    • hepatic don't start if ALT is > 2.5 ULN
  36. TZD advantages
    • decrease A1c .5-1.5
    • possible - increases HDL
    •                decrease triglycerides
  37. roles in therapy of TZD's
    • help with insulin resistance
    • PCOS - induce ovulation
  38. actos - pioglitazone dosing
    • 15-45 mg/day as a single dose
    • may be taken with or without food
  39. alpha-glucosidase inhibitors MOA
    inhibition of alpha glucosidase slows intestinal carbohydrate digestion and absorption
  40. alpha glucosidase inhibitors advantages
    • decrease A1c .5-1%
    • non-systemic
    • reduces post prandial glucose
  41. alpha glucosidase inhibitors adverse effects
    • GI - flatulence, possible liver enzyme elevations, abdominal pain, diarrhea
    • multiple dosing
    • medium cost
  42. alpha glucosidase inhibitors
    • acarbose - precose
    • miglitol - glyset
  43. alpha glucosidase inhibitors dosing
    • 25 mg TID, may start lower
    • maintenance 50 mg TID with meals
  44. GLP-1 agonists
    • exenatide - byetta (injectable)
    • exenatide - bydureon (extended release)
    • liraglutide - victoza (injectable)
  45. DPP-4 inhibitors
    • sitagliptin - januvia
    • linagliptin - tradjenta
    • saxagliptin - onglyza
  46. GLP-1 agonist MOA
    • increases insulin secretion
    • decrease glucagon secretion
    • slows gastric emptying
    • increases satiety
  47. GLP-1 advantages
    • weight reduction
    • decrease A1c 1-1.5%
    • potential for B cell mass/function
  48. GLP-1 disadvantages
    • GI - acute pancreatitis, N/V, diarrhea, HA
    • hypoglycemia - reduce OSA dose
    • thyroid cell cancer (rodents) - victoza
    • long term safety unknown
    • high cost
  49. byetta CI
    CrCl < 30
  50. byetta - exenatide dosing
    • 5 mcg BID
    • titrate to 10 mcg BID
  51. victoza - liraglutide dosing
    • 0.6 mg SC QD
    • max 1.8 mcg/day
    • independent of meals
  52. DPP-4 inhibitors MOA
    • increase GLP-1 concentration
    • increase insulin secretion
    • decreases glucagon secretion
  53. DPP-4 I advantages
    • decrease A1c .5-1
    • improves both fasting and postprandial levels
    • weight neutral
  54. DPP-4 I adverse effects
    • pancreatitis
    • itching, urticatia
    • increased URI incidences
    • dizziness
    • diarrhea
    • diaphoresis
  55. sitagliptin - Januvia dosing
    • 50 - 100 mg daily
    • 50 mg if CrCl <30-50ml/min
    • 25 mg if CrCl < 30ml/min
  56. saxagliptin - onglyza dosing
    • 2.5 - 5 mg daily
    • 2.5 mg daily if CrCl < 50ml/min
  57. lingaliptin - tradjenta dosing
    • 5 mg QD
    • no renal or hepatic dosing
  58. bile acid sequestrant
    colesevelam
  59. dopamine - 2 agonist
    bromocriptine
  60. bile acid sequestrants adverse effects
    • increases TG
    • interferes with medication absorption
    • constipation
  61. DA 2 agonist adverse effects
    • rhinitis
    • fatigue
    • dizziness
  62. DA 2 agonist MOA
    increases insulin sensitivity
  63. 5 factors contributing to metabolic syndrome
    • central obesity
    • high blood pressure
    • high triglycerides
    • low HDL
    • insulin resistance

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