**2. Hypertensive drugs**

Hypertension is a common condition associated with increased risk of stroke, heart failure, ischemic heart disease, and chronic renal failure. Thiazide diuretics, β-blockers, ACE inhibi‐ tors, angiotensin receptor blockers (ARBs) and calcium channel blockers (CCBs) are a com‐ mon first line treatment for hypertension [8].

Patients with the D allele may derive greater benefits from pharmacologic interventions with Beta-blocker treatment, probably through the decrease of sympathetic nervous sys‐

Drug Interactions, Pharmacogenomics and Cardiovascular Complication

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

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The effects of the CYP450 enzyme systems has been studied intensively during the last years and its role in the metabolism of drugs and other endogenous and exogenous chemicals is well defined. Numerous publications confirm the association of these enzymes with drugdrug, drug-toxins and drug-food interactions. Polymorphisms in the gene coding for the CYP2D6 isoenzyme, which catalyses the metabolism of β-blockers such as metoprolol, car‐ vedilol, timolol, and propranolol, may also affect blocker response. It has been demonstrat‐ ed that the clearance of the R(+) enantiomer of carvedilol was 66% lower and the area under the concentration-versus-time curve 156% higher among poor metabolizers than extensive

Some studies showed association with other genes. Genes involved in calcium signalling - CACNA1C, CACNB2, and KCNMB1- were found to be associated with myocardial infarc‐ tion or stroke with β-blockers versus calcium channel blockers [23-25]. Variable stroke risk by genotype was described for an MMP3 promoter polymorphism in patients treated with lisinopril [26] and different treatment-related outcomes with thiazides and β-blockers, but not diltiazem, by NEDD4L (protein reduce renal tubular expression of epithelial Na+ chan‐

Finally, the two studies by Schelleman et al reported no β-blocker interactions (for outcomes

Diuretics may act at a number of sites, including the proximal tubule, the Loop of Henle, and the distal and collecting tubules. Diuretics are thought to indirectly activate the reninangiotensin-aldosterone system and block sensitivity of blood vessels to catecholamines. Thiazide diuretics are the drug of choice for initial therapy, but genes responsible for renal

Antihypertensive response in black African Americans is found to be associated with locus at chromosome12q15 [30, 31] where the FRS2 gene is located, which is involved in fibroblast

Genome-wide association (GWA) studies are aimed at identifying common genetic variants modulating disease susceptibility, physiological traits and variable drug responses. These studies also provide further evidence for the large effects that single gene variants may exert for some drugs. GWA has explained relatively large proportions of variability compared to studies of traits such as disease susceptibility or physiological measurements. GWAS dem‐ onstrated that SNPs in lysozyme and Yeats domain-containing protein 4 (YEATS4 ) were as‐

Lynch et al. found that C carriers of the NPPA T2238C variant, which codes for the precur‐ sor of atrial natriuretic polypeptide, had more favourable clinical outcomes when treated

growth factor signalling. FRS2 plays a role in vascular smooth muscle cell regulation.

MI or stroke) variants of angiotensin receptor II type 1 (AGTR1) and ACE [28, 29].

sodium reabsorption can affect the patient's responsiveness to diuretic therapy.

tem activity [18].

metabolizers [19-22].

nel) genotype [27].

**2.2. Diuretics**

sociated with response to diuretic [30].

Despite availability of many effective agents, only about 40 percent [9] of treated hyperten‐ sive patients have their blood pressure controlled, mostly due to the unpredictable individu‐ al responses to treatment. Blood pressure responses to monotherapy vary widely within ethnic and gender subgroups [10].

Numerous studies have tried to establish associations between genetic polymorphisms and response to antihypertensive drugs. New developments in pharmacogenetics and pharma‐ cogenomics already offer in pharmacogenetics and pharmacogenomics already offers the opportunity to provide individualised drug therapy on the basis of a person's genetic make‐ up for some drugs, despite varied approaches in study designs and methodology. These tests are provided by several laboratories and available at some hospitals; pharmacogenetic methods will not only help to achieve treatment goals and limit adverse effects, but also avoid drug interactions.
