**7.1. Aspirin**

Pharmacogenetic studies of aspirin response to date have found associations with a few genes. It was reported that PLA2 (Leu59Pro) carriers, the variant in platelet glycoprotein IIIa, have impaired aspirin responses. After seven days of aspirin therapy in healthy volun‐ teers, plasma prothrombin fragment concentrations in bleeding-time wounds were reduced in 23 of 25 PLA1 homozygotes, compared with 9 of 15 PLA2 carriers [136]. A meta-analysis [137] of 50 polymorphisms in 11 genes reported in 31 studies with a combined sample size of 2834 subjects suggested that the common PLA1/2 polymorphism does confer aspirin re‐ sistance (odds ratio in healthy subjects=2.36; P=0.009); however, when combining both healthy subjects and those with cardiovascular disease, the odds ratio was 1.14 (P=0.40). The PLA2 allele occurs with a frequency of approximately 15% in humans and has been associat‐ ed with increased platelet activation and aggregation in vitro [138].

**8. Conclusion**

in drug metabolism.

laboratories (Table 1).

combinations.

escalate the cost for healthcare.

Adverse drug reactions (ADRs) have been reported to be the cause for drug withdrawal af‐ ter marketing, hospital admissions, death in hospitalised patients and to be the fourth lead‐ ing cause of death in developed countries. The costs associated with ADRs may radically

Drug Interactions, Pharmacogenomics and Cardiovascular Complication

http://dx.doi.org/10.5772/48423

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There is an increasing use of multiple medications to treat patients with chronic illnesses. Drug-drug interactions are common and growing in frequency due to increasing numbers of medications available and the number of patients on multiple medications. The knowledge of the pharmacodynamics and pharmacokinetics of the drugs helps to avoid unintended and problematic drug interactions. Several web sites, books, and cards are available for the clinician. The web sites are updated on a regular basis and are useful tools for prescribers.

The necessity to understand drug combination pharmacokinetics and pharmacodinamics in drug interactions is illustrated by the following example: a patient who is taking a drug equally cleared by CYP2D6 and CYP3A. That patient may not be at substantial risk for toxicity when treated with either a CYP2D6 or CYP3A inhibitor alone, but may be if treat‐ ed with both inhibitors at the same time [151]. Pharmacodynamic or pharmacokinetic drug interaction is a complex process and includes understanding of individual variations

Pharmacogenetics has a potential role in reducing ADRs at the pre-marketing and post-mar‐ keting stages of drug development and in clinical care. A priori identification of individuals at risk of developing ADRs for a given drug will help develop strategies to reduce the risk for ADRs in these patients. It can also be used to identify individuals at risk of developing serious ADRs and to treat these individuals with alternative therapy, thus converting ADRs

Although pharmacogenetics is a highly complex and ever-evolving science, it has amassed knowledge that can readily be used to provide efficient care to patients. It has been shown that gene variants that play a role in drug metabolism pathways can alter a patient's re‐ sponse or increase toxicity at normal dosage range, especially in combinational drug treat‐ ments. Pharmacogenetics seeks to understand the nature of variable drug responses. Several pharmacogenetics tests are already available for cardiovascular medications in biomedical

Pharmacogenetic findings may help to explain ethnic differences in drug response. The ac‐ cumulated facts of ethnic differences in cardiovascular drug responses and the fact that many genetic polymorphisms differ in frequency on the basis of ethnicity (example in the Western Sydney population, Fig. 1) will undoubtedly support future development of phar‐

It is possible that use of genetic and other patient-specific information, including envi‐ ronmental factors will help guide drug therapy decisions for certain drugs and drug

that are traditionally considered unavoidable to avoidable ADRs.

macogenetics in patient care and in drug interaction interpretation.

Associations between the PLA polymorphisms and subacute thrombosis after coronary in‐ tervention have been described in some reports [139-141] and it was shown that an in‐ creased risk of subacute thrombosis is associated with the PLA2 allele. In one study, the risk of subacute thrombosis after coronary angioplasty and stent placement was five times great‐ er in coronary artery disease patients with the PLA2 polymorphism than in patients homo‐ zygous for the PLA1 allele, despite similar antiplatelet therapy and similar clinical, angiographic and procedural characteristics [139].
