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TZDs also known as:
insulin sensitizers/insulin enhancers
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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
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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
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rosiglitazone metabolism and elimination
- hepatic metabolism
- elimination in urine (more) and feces (less)
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pioglitazone metabolism and elimination
- hepatic metabolism
- eliminated in feces
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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
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effect of TZDs on lipid
- rosiglitazone: inc cholesterol, LDL, HDL
- pioglitazone: inc HDL, dec TGs
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TZD contraindication
- Heart failure (especially rosiglitazone)
- - fluid retention
MI (rosiglitazone) - can only get with distribution program
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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
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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
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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
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