Meglitinides & TZDs

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Author:
jdonaldson
ID:
102217
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Meglitinides & TZDs
Updated:
2011-09-17 16:38:53
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james James donaldson Donaldson usp USP meglitinides Meglitinides diabetes Diabetes
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Neo, ba na na na na, sporin, ba na na na na na na, be nee nee nee
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  1. True or False?
    The meglitinides are more effective than the sulfonylureas?
    • False.
    • Use SUs when pts are > 1% above A1C goal.
  2. Whet medications are classified as meglitinides?
    • 1. nateglinide (Starlix)
    • 2. repaglinide (Prandin)
  3. True or False?
    Unlike the SUs, meglitinides do not cause hypoglycemia or weight gain.
    • False.
    • Their MOA is very similar to the SUs and therefore have a similar side effect profile.
  4. True or False?
    A synergistic relationship exists between the sulfonylureas and meglitinides.
    • False.
    • Their MOA is too similar.
  5. What drug is absolutely contraindicated with repaglinide? Why?
    • Gemfibrozil.
    • The half-life of repaglinide is increased.
    • (Trimethoprim also increases serum levels of repaglinide)
  6. Dosing for nateglinide -
    • 120 mg TID (1-30 mins ac meals), does not require titration.
    • 60 mg ac meals if A1C is close to goal.
  7. Dosing for repaglinide -
    • - A1C < 8% --> 0.5 mg po ac meals
    • - A1C ≥ 8% --> 1-2 mg po ac meals
    • (max 4 mg po ac meals [16 mg/day total])

    • *Administer 15 - 30 mins before meals
    • * If meal is skipped dose does not have to be taken
  8. True or False?
    Meglitinides should not be used in patients with renal insufficiency?
    • False.
    • They are a good option in patients with renal insufficiency.
  9. True or False?
    Meglitinides have a greater lowering effect on A1C compared to SUs.
    False
  10. True or False?
    Meglitinides have a lower risk of causing hypoglycemia compared to SUs.
    • True.
    • They are a good option for pts who develop hypoglycemia on low doses of SUs.
  11. What drugs are classified as TZDs?
    • 1. pioglitazone (Actos)
    • 2. rosiglitazone (Avandia)
  12. MOA of TZDs?
    Bind to PPAR-gamma, altering gene expression and indirectly increasing insulin sensitivity in the body.
  13. Major adverse effect of TZDs?
    Edema (especially when combined with insulin).
  14. What are the contraindications to TZDs?
    • NYHA class III/IV heart failure at initiation of therapy.
    • *Caution used with classes I and II (monitor closely).
    • *Use with this condition may lead to pulmonary edema and/or worsened HF.
  15. Dosing for pioglitazone -
    • Initiate at 15 - 30 mg once daily
    • Titrate to 45 mg daily max
  16. Dosing for rosiglitazone -
    • Initiate at 2 - 4 mg once daily
    • Titrate to 8 mg once daily or 4 mg BID
    • *(4 mg BID gives an additional 0.2 - 0.3 % lowering in A1C)
  17. What is the clinical implication of the TZDs MOA?
    As a nuclear ligand for PPAR-gamma, dose adjustments must be made every 4 - 6 weeks with max effect taking up to 12 weeks.
  18. Which TZD is rarely prescribed any longer due to a study published in the NEJM?
    • Rosiglitazone
    • (clinically neutral raise in TGs)
    • (10-15% raise in LDL)
    • (HR 1.43 for rate of MI vs other agents)
    • See table of notes pg. 25
  19. Monitoring of AST/ALT with TZDs is recommended at baseline and periodically thereafter. TZDs should not be initiated if AST/ALT is ≥ _____ UNL. If pt is already on a TZD, discontinue drug if AST/ALT is ≥ _______ UNL.
    • ≥ 2.5 x UNL
    • ≥ 3 x UNL
  20. Why should weight be checked at every medical visit for pts on TZDs if these drugs do not cause the release of insulin?
    Because an adverse effect of the TZDs is edema (which may cause or exacerbate CHF).
  21. True or False?
    Hemoglobin levels may decrease in a pt on a TZD.
    • True.
    • Dilutional anemia.
  22. True or False?
    TZDs as monotherapy may cause hypoglycemia.
    • False.
    • TZDs do not directly cause secretion of insulin. As monotherapy, they do not cause hypoglycemia.
  23. Women with PCOS or who are anovulatory may have an increased chance of becoming pregnant if on __________ or __________.
    • - TZDs
    • - Metformin
    • *Hence the TZDs are pregnancy category C
  24. True or False?
    Despite the contraindication for TZDs in pts with class III & IV CHF, many of these pts will receive them anyway.
    • True.
    • Monitor very frequently.
  25. While on a TZD a pt with CHF experiences worsening of the condition. What should be done?
    • - Stop the medication or reduce the dose
    • - If edema is present, give a diuretic (spironolactone has worked)
  26. TZDs increase the risk of __________ in women who are post-__________. This does not exclude them from taking these drugs, but they should be assessed for risk factors and monitored more frequently.
    • - fracture
    • - post-menopausal
  27. The duration of action of TZDs is _________.
    > 24 hours

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