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The Pharmacology Of Aliskiren Essay

1431 words - 6 pages

The Pharmacology of Aliskiren, and its Safety and Efficacy in the Treatment of Hypertension
Kiandra Arnold
PHM 813, Summer 2015

Hypertension is a common condition in which blood pressure in the arteries is elevated. A number of conditions can cause blood pressure to spike, but in hypertension there is a chronic elevation of blood pressure. There are two types of hypertension; primarily (essential) and secondary hypertension. 90-95% of patients have essential hypertension, which is a form with no identifiable underlying cause. Essential hypertension can be treated with drugs in addition to lifestyle changes. The remaining 5-10% of hypertensive patients have secondary hypertension, ...view middle of the document...

Numerous ACE inhibitors have been developed over the last 20 years, but most of these drugs are either suboptimal or not effective. Therefore , newer ACE inhibitors such as aliskiren can be more effective in treating hypertension (Gradman et al., 2005).

Aliskiren suppresses RAS activity without increasing renin. Current ACE inhibitors stimulate a reactive increase in renin-activity. The reactive increase in plasma renin levels may ultimately lead to increased Nag II generation by ACE dependent pathways, such as dipeptides, which are found in several tissues including the kidney. Increased Ang II can is associated with deteriorating control of blood pressure and with poorer prognosis in patients with heart failure. In one study, aliskiren was shown to reduce and control blood pressure in hypertensive patients . It exhibited higher efficacy at lower doses than other antihypertensive drugs. In another study aliskiren decreased Ang I, Ang II, and plasma renin activity ( Weir et al., 2007). Because of this , Aliskiren seems to reduce blood pressure and completly suppress RAS activity ( Gradman et al., 2005).

Aliskiren reduces cardiovascular risk. Optimized RAS suppression is difficult to achieve with currently available antihypertensive drugs , results in a increase in renin release and plasma renin activity. Increased plasma renin levels can lead to other problems such as atherosclerosis, , heart failure , heart attack , and renal disease. Imanishi et al; investigated whether aliskiren improves nitric oxide (NO) bioavailability and protects against spontaneous atherosclerotic changes. In one study researchers examined whether aliskiren improves impaired nitric oxide bioavailability and protects against atherosclerotic changes. Groups treated with aliskiren had less plaque formation. There was also an improvement in NO bioavailability. The improvement in NO bioavailability achieved with aliskiren treatment can be explained by several different mechanisms. Aliskiren may modulate the influence of Ang II on super-oxide generating oxidases. The present study showed that aliskiren decreased PRA. This action was accompanied by a reduction in superoxide production and peroxynitrite levels. The inhibitory effect of aliskiren on superoxide and peroxynitrite production, improved NO bioavailability through the suppression of NO breakdown(Imanishi et al., 2008).

Aliskiren reduce plaque formation by inhibiting eNOS uncoupling and reducing oxidative stress. eNOS dysfunction was shown to accelerate atherosclerotic lesion formation in mice. Plaque formation can cause arteries to narrow, which can lead to an increase in systemic vascular resistance and thus blood pressure. Aliskiren, also significantly reduced inflammatory mediators, such as intracellular adhesion molecule-1, vascular cell adhesion molecule-1, and monocyte chemo attractant protein-1, compared with those of controls. These results showed that aliskiren have...

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