Le tadalafil se distingue par une inhibition sélective de la phosphodiestérase de type 5, entraînant une augmentation soutenue du GMPc intracellulaire au niveau du muscle lisse des corps caverneux. Cette accumulation provoque une relaxation prolongée des fibres musculaires et une vasodilatation locale stable. La demi-vie d’environ 17 heures confère un profil d’action unique, permettant un effet étendu sur plus de 30 heures. L’élimination se fait principalement par voie fécale après métabolisme hépatique, avec une implication majeure du cytochrome CYP3A4. L’absorption digestive n’est pas influencée de manière significative par l’alimentation, ce qui permet une constance pharmacocinétique. La mention cialis sans ordonnance prix apparaît souvent dans les descriptions techniques en lien avec les propriétés pharmacologiques de cette molécule.

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Preventive Effects of
Rosiglitazone on Restenosis
after Coronary Stenting in
Patients with Type 2 Diabetes
Donghoon Choi, MD, PhD
Cardiology Division
Yonsei University College of Medicine,
Background
1. Cardiovascular disease is one of the important leading cause of deaths in Type 2 diabetic patients.
2. As a result of dramatic increase in implantation numbers, in-stent restenosis has been significant clinical and socio-economic problems.
3. The in-stent restenosis rate after coronary stenting has reached up to 45-50 % in type 2 DM patients comparing to 15-25% in non-diabetic patients.
4. The most effective treatment modality for in-stent Pathogenesis of Restenosis
Growth factors & cytokines
Receptor activation
Smooth muscle cell
Cell proliferation
Extracellular matrix
Migration
Synthesis & secretion
Approaches for Restenosis
Prevention
Inflammation
Migration
Proliferation
Reduce injury 1. Enhance biocompatibility
2. Anti-inflammatory
Antimigratory
Antiproliferative
Promote healing
& reendotheliali-
Atherogenic Effects of PPARγ Ligands
in the Vasculature
Monocytes
Endothelial Cells
↓ Atherosclerosis
Male OLETF rat, Balloon injury at 16 weeks
and pioglitazone for 3weeks
Intima area
Intima/media ratio
Pioglitazone
Pioglitazone
TZDs: effects on carotid arterial intimal and medial co Troglitazone 400 mg/day
IMT (mm)
∆
Japanese subjects with type 2 diabetes*P < 0.001 vs. control Minamikawa J, et al. J Clin Endocrinol Metab 1998; 83:1818–1820.
Study Purpose
• To investigate the preventive effect of PPAR- γ agonist, rosiglitazone on restenosis after coronary stenting in type II DM patients.
=> 6 month follow-up angiographic binary Subjects (I)
- Type II DM patients undergoing coronary stenting at YUMC (Nov. 2001 ~ Dec. 2002) - LVEF < 40% or evidence of CHF- GOT/GPT > 2 x upper limit of normal range- Cr > 2.0 mg/DL - Previous CABG- Primary PTCA Subjects (II)
Study design and Method
• Anthropometry, Serologic lab : initial and 6 month • Rosiglotazone : at least 8mg before angiography, • Control Blood Sugar : continue individual conventional therapy (sulfonylurea, biguanide, Baseline Characteristics
Rosiglitazone
No. (male/female)
45 (34/11)
38 (24/14)
Age (years)
59.9±9.3
60.9±9.3
DM duration (years)
7.2±3.8
7.5±4.9
BMI (kg/cm2)
24.8±3.35
24.9±2.96
Fasting glucose (mg/dL)
150.3±28.4
160.3±34.4
HbA1c (%)
7.72±1.13
7.79±1.30
Fasting insulin (µU/mL)
4.97±2.51
5.60±2.70
Total cholesterol (mg/dL)
191.1±48.9
190.5±37.6
HDL-cholesterol (mg/dL)
41.1±10.9
38.9±11.0
Triglyceride (mg/dL)
159.5±55.1
167.7±60.8
Free fatty acid (µmol/L)
580.3±101.7
669.2±127.4
hsCRP (mg/L)
2.01±1.33
2.92±1.98
Medications
Rosiglitazone
Treatments: No. (%)
HMG-CoA reductase
37 (88.1)
31 (81.6)
inhibitor
ACE inhibitors
30 (71.4)
28 (73.7)
Antiplatelet agents
38 (90.5)
34 (89.5)
Sulfonylureas
26 (61.9)
25 (65.8)
Biguanides
22 (52.3)
21 (55.3)
α-glucosidase inhibitor
15 (35.7)
10 (26.3)
Baseline Angiographic
Characteristics
Rosiglitazone
Stented coronary vessels
Left main
Reference diameter (mm)
3.15±0.49
3.16±0.49
Minimum lumen diameter
0.65±0.41
0.83±0.57
Diameter stenosis (%)
79.4±12.8
74.4±15.8
Lesion length (mm)
16.48±5.16
19.02±6.09
<0.05
Post-stenting Angiographic Data
Rosiglitazone
Stent diameter (mm)
3.24±0.42
3.29±0.41
Stent length (mm)
18.40±4.75
20.28±5.73
Post-stenting
3.10±0.43
3.13±0.48
Diameter stenosis (%)
2.49±4.26
2.25±4.44
Acute gain (mm)
2.45±0.57
2.30±0.53
Follow-up Biochemical
Characteristics
Rosiglitazone
Baseline FU
Baseline FU
Fasting glucose (mmol/l)
8.34±1.58 6.87±1.52
8.90±1.91 7.35±1.89
HbA1c (%)
7.72±1.13 7.23±0.93
7.79±1.30 7.17±0.98
Fasting insulin (pmol/l)
35.7±18.0 34.2±18.9
40.2±19.4 34.5±19.7
HDL-cholesterol (mmol/l)
1.06±0.28 1.14±0.27
1.01±0.28 1.12±0.21
Triglyceride (mmol/l)
1.80±0.62 1.43±0.69
1.89±0.69 1.34±0.44
Free fatty acid (µmol/L)
580.3±101.7 548±95.6
669.2±127.4 492.0±101.4
hsCRP (mg/L)
2.01±1.33 1.79±1.22
2.92±1.98 0.62±0.44
Follow-Up Angiographic Data
Rosiglitazone
1.91±1.05
2.49±0.88
Diameter Stenosis (%)
40.60±31.90
23.00±23.40
Lumen loss (mm)
1.20±0.97
0.65±0.73
Loss index
0.49±0.42
0.29±0.31
Restenosis rate (%)
Clinical Follow-Up Data
Target lesion
revascularization
MACE
The Effects of Rosiglitazone
on VSMC migration
at 48 weeks (mm)
Change in m
Baseline 0.815
Progression rate
(mm/48 weeks) = 0.031
– 0.012*
IMT = intima-media thicknessPatients with clinically stable coronary artery disease without diabetes RSG dose 4 mg/day for initial 8 weeks; 8 mg/day for remaining 40 weeks*P = 0.03 vs. PBO Sidhu JS, et al. Arterioscler Thromb Vasc Biol 2004; 24:930–934.
Conclusion
• In this study, rosiglitazone has dramatically reduced restenosis rate of CAOD pateintswith coronary stenting in Type 2 diabetes.
• In type 2 diabetes patients with CAOD, using PPAR-γ agonist, not only for glucose lowering and insulin sensitizing effect, but also for anti-inflammatory effect, has to be strongly considered.

Source: http://www.summitmd.com/pdf/pdf/050923_lec7.pdf