Pharmacy & Therapeutics - February 2008 - (Page 92)

DRUG FORECAST Aliskiren (Tekturna), A Novel Antihypertensive Approach to Inhibition of the Renin– Angiotensin–Aldosterone System Julie Cromer, PharmD, and Simona Peker, BS, MS/MLS, MSA, PharmD INTRODUCTION Hypertension is defined as a systolic blood pressure (BP) of 140 mm Hg or higher, a diastolic BP of 90 mm Hg or higher, or the need to take an antihypertensive drug.1 The prevalence of hypertension in America has reached epidemic proportions; almost 72 million adults (nearly one in three) have hypertension.2 The implications of this prevalence are devastating. Hypertension is strongly associated with ischemic heart disease and stroke, and the risk of mortality from these conditions is doubled with every increase of 20 mm Hg in systolic BP or of 10 mm Hg in diastolic BP. Even small increases in BP (values up to 130–139/ 85–89 mm Hg), when compared to normotensive levels (120/80 mm Hg or below), result in a doubling of the relative risk of cardiovascular disease.1 PATHOPHYSIOLOGY OF HYPERTENSION The key components contributing to BP are (1) cardiac output, as determined by heart rate and the volume contained in the intravascular space, and (2) the degree of constriction, or resistance in the vascular walls. Most patients with elevated BP are considered to have “essential” hyper tension, whereas a small percentage have secondary hypertension resulting from underlying renal or adrenal insufficiencies. For patients with essential hypertension, increased BP typically results from increased peripheral resistance, whereas cardiac output remains normal. Increased peripheral resistance is a result of contraction of the smooth muscle in the small arterioles; prolonged contraction, in turn, results in a thickening of the vascular walls, yielding an irreversibly increased resistance. The pathophysiology of hypertension varies among age groups (Figure 1). Younger, healthier patients with elevated BP are more likely to have a normalvolume, high-cardiac-output form of hypertension. These patients usually benefit from medications that decrease cardiac output by decreasing heart rate and decrease peripheral resistance by causing vasodilation. As people age, cardiac output naturally declines, as does kidney function, leading to low-cardiacoutput, high-volume hypertension. These CLASSIFICATION OF HYPERTENSION As a result of the Seventh Report of the Joint National Committee in 2004, hypertension is now stratified into four classes: normal, pre-hypertension, stage 1, and stage 2 (Table 1). The addition of a prehypertension class resulted from evidence that patients with BP in the range of 130–139/80–89 mm Hg had twice the likelihood of later developing hypertension than patients with lower BP values.3 Disclosure: The authors have no commercial or industrial relationships to disclose in regard to this article. Dr. Cromer is a Pharmacy Practice Resident, and Dr. Peker is Pharmacy Residency Director, both at the Veterans Affairs Medical Center at the New York Harbor Healthcare System in New York, New York. Drug Forecast is a regular department coordinated by Alan Caspi, PhD, PharmD, MBA, President of Caspi & Associates in New York. patients obtain little benefit from drugs that lower heart rate, because they already have a reduced cardiac output. Medications that reduce volume are usually more effective. All current antihypertensive therapies decrease BP by modifying one or more of the aforementioned components. Older treatments, such as beta blockers, alpha blockers and agonists, direct vasodilators, and calcium-channel blockers, were aimed primarily at reducing the heart rate and peripheral vascular resistance. Diuretics are used to reduce volume directly. Unfor tunately, mono therapy with any of these agents is seldom sufficient, and patients typically require two or more antihypertensive medications from different classes before their BP can be considered controlled. Most recent on the antihypertensive forefront are drugs targeted at the reninangiotensin-aldosterone system (RAAS). These drugs are classified as angio tensin-converting enzyme (ACE)–inhibitors and angiotensin-receptor blockers (ARBs). The Renin–Angiotensin– Aldosterone System The importance of the RAAS is well established; the RAAS affects cardiovascular, cerebrovascular, and renal function. Drugs that inhibit the RAAS have proven ability to reduce BP, to prevent Table 1 Classification of Hypertension Systolic Blood Pressure (mm Hg) Normal Pre-hypertension Stage 1 hypertension Stage 2 hypertension Below 120 120–139 140–159 160 or higher Diastolic Blood Pressure (mm Hg) and below 80 or 80–89 or 90–99 100 or higher Data from Chobanian AV, Bakris GL, Black HR, et al. JAMA 2003;289(19):2560–2572.1 92 P&T® • February 2008 • Vol. 33 No. 2

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Pharmacy & Therapeutics - February 2008 Contents Editorial Medication Errors Prescription: Washington The Language of (Forgive Us) Change, As P&T Enters the Digital Age New Drugs/Drug News/New Medical Devices Drug Forecast Use and Outcomes of Antifibrinolytic Therapy in Patients Undergoing Cardiothoracic Surgery at 20 Academic Medical Centers in the United States Evaluation of the Management of Acute Venous Thromboembolism and Its Outcomes: One Institution's Experience American Society of Hematology, 49th Annual Meeting Pharmaceutical Approval Update

Pharmacy & Therapeutics - February 2008

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