PubMed · 13671997
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H WALTER. 1959-06-20. [Possible labor acceleration with spasmolytics].. https://pubmed.ncbi.nlm.nih.gov/13671997/
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Personalized medicine is based on a better knowledge of biological variability, considering the important part due to genetics. When trying to identify involved genes and their products in differential cardiovascular drug responses, a five-step strategy is to be followed: 1) Pharmacokinetic-related genes and phenotypes (2) Pharmacodynamic targets, genes and products (3) Cardiovascular diseases and risks depending on specific or large metabolic cycles (4) Physiological variations of previously identified genes and proteins (5) Environment influences on them. After summarizing the most well-known genes involved in drug metabolism, we will take as example of drugs, the statins, considered as very important drugs from a Public-Health standpoint, but also for economical reasons. These drugs respond differently in human depending on multiple polymorphisms. We will give examples with common ApoE polymorphisms influencing the hypolipemic effects of statins. These drugs also have pleiotropic effects and decrease inflammatory markers. This illustrates the need to separate clinical diseases phenotypes in specific metabolic pathways, which could propose other classifications, of diseases and related genes. Hypertension is also a good example of clinical phenotype which should be followed after various therapeutic approaches by genes polymorphisms and proteins markers. Gene products are under clear environmental expression variations such as age, body mass index and obesity, alcohol, tobacco and dietary interventions which are the first therapeutical actions taken in cardiovascular diseases. But at each of the five steps, within a pharmacoproteomic strategy, we also need to use available information from peptides, proteins and metabolites, which usually are the gene products. A profiling approach, i.e., dealing with genomics, but now also with proteomics, is to be used. In conclusion, the profiling, as well as the large amount of data, will more than before render necessary an organized interpretation of DNA, RNA as well as proteins variations, both at individual and population level.
Cardiovascular disease (CVD) is the major cause of death in developed countries and is rapidly becoming the major cause of death in the developing world. The increasing rates of obesity and type 2 diabetes, however, may slow the current favorable trends for deaths attributable to CVD in many developed countries. To improve control of risk factors for CVD, Wald and Law proposed a "polypill," containing a statin, a diuretic, a beta-blocker, an angiotensin-converting enzyme inhibitor, aspirin, and folic acid. This combination pharmacotherapy (CP) could be made widely available without treating specific risk factors or individuals. A workshop sponsored by the Centers for Disease Control and Prevention reviewed the concept of CP for both primary and secondary prevention. Combination pharmacotherapy may prove to be efficacious but may also have side effects and poor adherence, which may be greater than or less than that of other preventive approaches. Randomized trials are needed to study these issues, although the design for such trials is uncertain. The ability of CP to prevent CVD in a cost-effective manner must be demonstrated. Minority groups and people with low socioeconomic status in the United States have an increased risk for CVD, and the effectiveness of such pharmacotherapy must be considered for these populations. Combination pharmacotherapy may prove especially effective in the developing world, where studies of CP may precede those done in wealthier countries. Combination pharmacotherapy may have tremendous potential, but additional study and detailed evaluation are necessary.
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