Die Struktur von Tadalafil erlaubt eine selektive Bindung an die Bindungsstelle der PDE5 und minimiert gleichzeitig die Interaktion mit PDE6, was visuelle Nebenwirkungen einschränkt. Seine Verteilung im Organismus erfolgt breit, wobei das Verteilungsvolumen etwa 63 Liter beträgt. Über 90 % des Wirkstoffs sind an Plasmaproteine gebunden. Die Wirkung bleibt unabhängig von der Nahrungsaufnahme konstant. Der Abbauweg über CYP3A4 kann durch Hemmer wie Ritonavir oder Ketoconazol verlangsamt werden, was die Plasmakonzentrationen deutlich erhöht. In diesem Kontext wird cialis 20mg preis häufig in Bezug auf pharmakokinetische Wechselwirkungen erwähnt.

Microsoft powerpoint - scottfreeland

UPDATES IN CARDIOLOGY
DECEMBER 4, 2009
Drug-Drug Interactions
Drug Interactions
ƒ Pharmacodynamics (PD):
„ What the drug does to the body ƒ Pharmacokinetics (PK):
„ What the body does to the drug ƒ Primary source for drug interactions
CYP-450 Enzymes
CYP-2E1 CYP-1A2
Deficient in 7% of caucasions
Adapted from Pharmacotherapy 15:848-998, 1995
Clopidogrel and Proton
Pump Inhibitors (PPI’s)
ƒ > 100 million combined prescriptions /yr
„ 2008 ACC/AHA/ACG Clinical Expert Consensus Document„ 2007 ACC/AHA Unstable Angina/NESTMI Guidelines Clopidogrel – “Prodrug”
ƒ Converted to its active form by metabolic enzymes (CYP450- ƒ PPI’s
„ Inhibits the activity of CYP-450 (2C19) enzyme
„ Reduced activity/efficacy of clopidogrel
‡ Platelet Inhibition Reactivity (PRI) – lab assay „ Higher platelet activity compared with „ Higher observed rates of MACE (AMI; Stent Clopidogrel + PPI’s
„ COGENT trial – No difference in clinical events Clopidogrel + PPI’s
‡ Omeprazole ~ esomeprazole >>> pantoprazole > „ PPI: Pantoprazole / Lansoprazole / Rabeprazole Prasugrel (Effiant®) and PPI’s
CYP (3A4 / 2B6) >>>> CYP(2C9) and CYP (2C19)
Conclusions: not affected by concurrent PPI’s Ticagrelor (Investigational) – Not affected DRONEDARONE (Multaq®)
Added methane sulfonyl
group shortened T½ and
Dronedarone
reduce accumulations
Amiodarone
Dronedarone (Multaq®)
„ Dronedarone increases digoxin exposure by 2.5 fold „ Follow similar dosing guidelines as amiodarone when Warfarin
„ Dronedarone increased S-warfarin isomer by 1.2 fold „ No observed excess risk of bleeding when dronedarone „ No dosage adjustment of warfarin required
Simvastatin
„ Dronedarone ↑ simvastatin exposure by 4 fold „ Recommend following same guidelines as amiodarone Not a Class Effect
Lipophilic
Hydrophlic
Higher rate of Drug
Lower rate of Drug Interactions
Interactions
Use if potential drug
interactions due to CYP-450
metabolism
ED drugs and Nitrates
Concurrent Drug
Findings
RECOMMENDAITON
Nitrates + PDE
Combination -
contraindicated
The length of time required
Nitrates
between discontinuation of
nitroglycerin therapy and
safe administration of
Nitroprusside
sildenafil, etc. is not
Alpha Blocker
Recommendations:
(Cardura, Hytrin)
Sildanafil (T½ 4hr) > 24hrs
Tacalafil (T½ 17hr) > 24 hrs
Vardenafil (T½ 4hr) > 24 ?
CYP- 450(3A4)
(INHIBITORS)
ƒErythromycin
ƒAntifungal

Source: http://www.cardiofoundation.org/educational_series/presentations/09_richter_lecture/Scott%20Freeland%20DrugInt.pdf