All Diabeetus

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Author:
jcu1
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236878
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All Diabeetus
Updated:
2013-09-24 20:08:31
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Endo
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Dr. Drab
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  1. Secretagogues classes
    • sulfonylureas
    • meglitinides
  2. Antihyperglycemics
    • biguanides
    • thiazolidinediones
    • alpha-glucosidase inhibitors
    • bile acid sequestrants
    • dopamine agonist
    • SGLT-2 inhibitors
  3. part secretagogues and antihyperglycemic properties
    DPP4-inhibitors
  4. incretin mimetic
    GLP-1 receptor agonist
  5. postprandial effects
    • alpha-glucosidase inhibitos
    • amylinomimetic
    • bile acid sequestrants
    • dopamine agonists
    • DPP-4 inhibitors
    • GLP-1 agonists
    • prandial insulin
  6. fasting effects
    • biguanides
    • SGLT-2 inhibitors
    • sulfonylureas
    • TZDs
    • basal insulin
  7. Classes that will cause weight gain
    • sulfonylurea
    • TZDs
    • insulin
  8. Classes that will cause weight loss/neutral
    • metformin (n/l)
    • DPP-4 inhibitor (n)
    • GLP-1 agonist (l)
  9. known to cause hypoglycemia
    • sulfonylureas
    • insulin
  10. Sulfonylureas MOA
    stimulate insulin release from beta cells on pancreas

    binds receptor closing K channel --> depolarizes cell membrane and opens Ca channel --> Ca in, insulin out
  11. first generation sulfs
    • tolbutamide
    • acetohexamide
    • tolazamide
    • chlorpropamide
  12. 1st gen sulf that has a very long half life
    chlorpropamide - 35h
  13. Metabolism and elimination of sulfonylureas
    Metabolized in liver; renally excreted
  14. second gen sulfs
    • glyburide
    • glyburide micronized
    • glipizide
    • glimepiride
  15. hypoglycemic action made worse by:
    quinolones (worse)

    • NSAIDs
    • beta blockers
    • fluoxtine
  16. sulfonylureas contraindications
    • type 1 DM
    • diabetic ketoacidosis
  17. Sulfonyureas side effects
    • hypoglycemia (big one)
    • weight gain
    • hematologic (leukopenia, thrombocytopenia, anemia)
    • dermatological (rash, puritis, purpura)
    • GI (N/V, cholestasis)
  18. chlorpropamide specific side effects
    • disulfiram-like rxn
    • hyponatremia
    • cholestatic jaundice
  19. Meglitinides/phenylalanines in combination
    repaglinide and nateglinide often used in combo with metformin and TZDs
  20. meglitinides MOA
    • stimulates insulin release from beta cells
    • insulin levels rise with postprandial glucose peak at:
    • nateglinide 45 min (DOA 3-4h)
    • repaglinide 60 min (DOA 4-6h)
  21. meglitinides target fasting or post prandial
    post prandial
  22. meglitinides insulin release glucose dependent or independent
    dependent - less hypoglycemia
  23. meglitinides compared to sulfs
    • shorter duration of action
    • more glucose dependent stimulation of insulin release --> less hypoglycemia
  24. repaglinide metabolism and elimination
    • metabolism: liver (inactive metabolites)
    • elimination: feces
  25. nateglinide metabolism and elimination
    metabolism: liver (less potent metabolites)

    elimination: urine
  26. nateglinide vs. repaglinide
    onset/DOA
    potency
    • nateglinide more rapid onset and shorter DOA
    • repaglinide more potent
  27. meglitinide contraindications
    • type 1 dm
    • diabetic ketoacidosis
    • repaglinide + gemfibrozil
  28. repaglinide has DDI with what? why?
    gemfibrozil

    • rep metabolized by CYP 2C8
    • gem is CYP 2C8 inhibitor
    • --> 8x inc in repaglinide; 3x t1/2
  29. meglitinides side effects
    • hypoglycemia (less than sulf; great with repaglinide+gemfibrozil)
    • weight gain
    • headache
    • URI
    • dizziness
    • neuromuscular (arthralgia, back pain, paresthesia)
    • GI (N/D/C, epigastric fullness, heartburn)
  30. when to take a meglitinide
    take 15 min bf a meal (can be taken up to 30 min before the meal)
  31. missing a meal with meglitinide
    • skip a dose if meal is skipped
    • add dose if extra meal eaten
  32. Alpha-glucosidease inhibitors MOA
    • inhibits action of intestinal amylase and alpha-glucosidase action
    • causes delay in breakdown of complex carbs to glucose --> glucose absorbed in distal part of SI and peak postprandial bg conc reduced
  33. alpha-glucosidase inhibitor affects fasting or post prandial?
    post pranidal (decreases bg peak)
  34. alpha-glucosidase inhibitors
    • acarbose
    • miglitol
  35. alpha-glucosidase inhibitors metabolism and elimination
    • metabolism: none
    • acarbose elim: excreted in feces
    • miglitol elim: unchanged; renally
  36. when to take alpha-glucosidase inhibitor
    • with first bite of each meal
    • want the drug mixed with food to inhibit the enzyme
  37. alpha-glucosidase inhibitor potency
    • weak compared to other agents
    • good for ppl with early disease (mildly elevated A1C -> normal FBG and high PPG)
  38. alpha-glucosidase inhibitors and simple sugars
    no effect
  39. alpha-glucosidase inhibitor contraindication
    • inflammatory bowl disease
    • colonic ulceration
    • partial intestinal obstruction
    • other chronic intestinal diseases
  40. alpha-glucosidase inhibitors side effects
    • GI (gas, ab pain, diarrhea) --> reduce in 4-8 wks or with dose reduction
    • inc in transaminases (dose related)
    • hypoglycemia when used in combo
  41. alpha-glucosidase inhibitor DDIs
    • charcoal
    • digestive enzymes
  42. Metformin MOA
    • 1. decreases hepatic glucose production
    • 2. improve insulin sensitivity and dec intestinal absorption of glucose
  43. Metformin elimination
    urinary excretion
  44. metformin starting dose elderly and non elderly
    • noneld: 500-1000mg
    • eld: 500 mg
  45. metformin and endothelial function
    • improves
    • inc Ach stimulated arterial blood flow in PVD
  46. Metformin Contraindications
    • SCr ≥1.5 (males) 
    • SCr ≥1.4 (females)
    • CrCl < 60 ml/min

    • acute or chronic metabolic acidosis
    • radiologic studies w/ iodinated contrast materials (+ 48 hrs after)--> renal dysfuntion
  47. Metformin precautions
    • ≥ 80 yrs; not max dose
    • meds that affect renal fx (cationic drugs --> amiloride, digoxin, procainamide, quinidine, ranitidine, triamterene trimethoprim)
    • conditions predisposing pt to renal insufficiency or hypoxia (CHF, COPD, shock, MI)
    • before surgical procedures
    • alcohol --> lactate metabolism pts
    • hepatic disease
  48. metformin side effects
    • GI: diarrhea (slow titration), N/V, epigastric fullness
    • Dermatologic: rash, photosensitivity, urticaria
    • dec vitamin B12 absorption: anemia
    • lactic acidosis: rare
  49. TZDs also known as:
    insulin sensitizers/insulin enhancers
  50. TZD MOA
    direct stimulation of PPAR-gamma --> inc in GLUT-4 on cell surface --> increase in insulin uptake in muscle and adipose and dec in hepatic glucose production
  51. Diff btwn TZD's and metformin
    MOAs

    • metformin: 1-dec hepatic glucose output; 2-better insulin sensitivity in muscle and adipose
    • TZD: 1-better insulin sensitivity in muscle and adipose; 2-dec hepatic glucose output
  52. rosiglitazone metabolism and elimination
    • hepatic metabolism
    • elimination in urine (more) and feces (less)
  53. pioglitazone metabolism and elimination
    • hepatic metabolism
    • eliminated in feces
  54. TZD's effects seen when?
    • dec in BG seen in 2-4 wks
    • full effects in up to 12 wks
    • perseverance of effect for 1-2 yrs
  55. effect of TZDs on lipid
    • rosiglitazone: inc cholesterol, LDL, HDL
    • pioglitazone: inc HDL, dec TGs
  56. TZD contraindication
    • Heart failure (especially rosiglitazone)
    • - fluid retention

    MI (rosiglitazone) - can only get with distribution program
  57. pioglitzone precautions
    • heart failure inc risk (lowest dose if in Class 2 HF)
    • macular edema (use with caution in pts with edema)
    • more bone fracture in women
    • resumption of ovulation in perimenopausal anovulatroy women
    • bladder cancer
  58. TZD side effects
    • no signs of hepatotoxicity
    • rosi: MI, death from CV causes
    • pio: bladder cancer
    • weight gain (dose dependent)
    • edema (dose dependent; more common with insulin)
    • dec in Hbg and Hct (bc of fluid imbalance)
    • resumption of ovulation
    • bone fracture
    • macular edema
  59. TZD monitoring
    • LFTs b4 starting
    • don't start if ALT > 2.5x upper limit
    • get LFT's at first signs of hepatic dysfuntion (fatigue, anorexia, nausea, vomiting, ab pain, dark urine, jaundice) -->if continues, d/c
  60. DPP-4 inhibitor drugs
    • sitagliptin
    • saxagliptin
    • linagliptin
    • alogliptin
  61. DPP-4 MOA
    • inhibits DPP-4 enzyme - increases and prolong ative incretin levels
    • inc insulin release and dec glucagon secretion (glucose dependent)
  62. metabolism and elimination of DPP-4 inhibitor
    all renally excreted except linagliptin (excreted unchanged by enterohepatic system)
  63. sitagliptin contraindications
    nothing significant except hypersensitivity
  64. sitagliptin warning/precautions
    • pts with renal insufficiency (dosage adjustment in mod to severe renal insufficiency and ESRD)
    • use with meds that cause hypoglycemia (sulfonylureas)
    • hypersensitivity rxn with sitagliptin
    • pancreatitis
  65. sitagliptin DDIs
    none
  66. sitagliptin AEs
    hypoglycemia when in combo with sulfonylureas

    no other significant AEs
  67. DPP-4 inhibitor body weight
    no changes
  68. saxagliptin contraindications
    hypersensitivity
  69. saxagliptin precautions
    • be careful when used with a secretagogue
    • pancreatitis
  70. saxagliptin DDIs
    • coad with strong CYP3A4/5 inhibitors (ketoconazole) --> inc saxagliptin conc.
    • don't need to make adjustments when using with moderate inhibitors and inducers
  71. saxagliptin AEs
    • URI
    • UTI
    • headache
  72. linagliptin contraindication
    hypersensitivity
  73. linagliptin precautions
    hypoclycemia with secretagogue
  74. linagliptin DDI
    coadmin with strong P-GP and CYP3A4 inducer --> reduce efficacy of linagliptin (e.g. rifampin)
  75. linagliptin AEs
    • nasopharyngitis
    • arthralgia
    • back pain
    • headache
    • hypersensitivity
    • pancreatitis
  76. alogiptin contraindication
    hypersensitivity
  77. alogliptin warnings and precautions
    • hypoglycemia when with a secretagogue
    • pancreatitis
    • hepatic effects
  78. alogliptin excretiong
    renal
  79. alogliptin DDIs
    none
  80. alogliptin AE
    • nasopharyngitis
    • headache
    • URI
  81. unique part about SGLT2 inhibitors
    • no dependent on beta cell function or insulin resistance
    • less glucose in blood also decreases amt that the pancreas has to work
  82. SGLT-2 inhibitor MOA
    • inhibitor of SGLT2
    • blocks reabsorption of filtered glucose and reduce renal threshold for glucose
  83. SGLT-2 inhibitor drug
    canagliflozin
  84. SGLT-2 inhibitors CI
    • hypersensitivity
    • severe renal impairment (GFR < 30 ml/min; ESRD; on dialysis)
  85. SGLT-2 inhibitors precautions
    • hypotension (watch out for hypovolemia in pts with renal impairment, elderly, low systolic bp, or on diuretics, ACEi or ARB)
    • impaired renal fx
    • hyperkalemia
    • hypoglycemia with other meds that cause hypoglycemia
    • genital mycotic infections
    • inc LDL
  86. SGLT-2 inhibitors DDIs
    • digoxin - inc AUC and Cmax
    • inducers of UGT 1A9 and UGT2BB (rifampin, ritonavir, phenobarbital, phenytoin)

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