People for whom certain genetic variations hinder the metabolism of a certain drug, thus making that drug either ineffective or toxic, should simply not be prescribed that specific drug. However, the real picture

is slightly more complicated. There are four criteria for judging the clinical usefulness of pharmacogenomics. Firstly, the strength of association with the clinical problem is essential. Clearly, if the strength of association is low, so is the use of pharmacogenomics. Secondly, we need to evaluate the clinical importance of the specific clinical problem to justify the use of pharmacogenomics. Trivial medical Inhibitors,research,lifescience,medical problems do not warrant the use of pharmacogenomics. Thirdly, we need to factor in the predictiveness of pharmacogenomics for the individual patient, and lastly, other available treatment options must be considered. Inhibitors,research,lifescience,medical These four factors must be taken into account when bringing pharmacogenomics into the practice of medicine. CARDIOVASCULAR DISEASE, LATE STENT THROMBOSIS, AND PHARMACOGENOMICS Heart disease fits the criterion of clinical importance.

Inhibitors,research,lifescience,medical More than 2,200 Americans die of cardiovascular disease (CVD) each day,2 and there are many pharmacogenomic implications for CVD.3–5 If a life-saving drug was shown to be less effective for people who carry a certain genetic marker, and, even more pertinent, if as a result of this genetic predisposition they were at risk if given a certain drug, it is clearly medically relevant. One common procedure performed on patients with acute CVD is stenting. Over 1 Inhibitors,research,lifescience,medical million stent procedures are first annually performed in the United States.6 Although drug-eluting stents have been very successful in preventing re-narrowing, or restenosis Inhibitors,research,lifescience,medical of the coronary arteries, these stents carry a slight increase in risk for late stent thrombosis (Figure 1). The occurrence of late stent thrombosis

is the result of several factors such as incomplete stent apposition. The frequency of late stent thrombosis occurrence is low, but the risk continues over time. Despite the low frequency, the clinical implication of stent thrombosis is dire since the chance of death or myocardial infarction from stent thrombosis Entinostat is 40%–60%. Therefore, patients with drug-eluting stents are treated with dual selleck chemical antiplatelet therapy (aspirin plus clopidogrel, ticagrelor, or prasugrel) for the recommended duration. Figure 1 Stent thrombosis. ANTIPLATELET THERAPY AND CLOPIDOGREL The antiplatelet therapy drug, clopidogrel (Plavix®) is a prodrug which is activated in the liver in a two-step process by cytochrome P450 enzymes (Figure 2). The bioavailability of clopidogrel is determined by the genetic make-up of these enzymes and other enzymes in addition to intestinal absorption. Clopidogrel acts upon an ADP receptor that is found on platelet cell membranes.