Renin inhibitors - Australian Prescriber

2. Zeitz CJ, Campbell DJ, Horowitz JD. Myocardial uptake andbiochemical and hemodynamic effects of ACE inhibitors inhumans. Hypertension 2003;41:482-7.3. Campbell DJ, Krum H, Esler MD. Losartan increasesbradykinin levels in hypertensive humans. Circulation2005;111:315-20.4. Wood JM, Maibaum J, Rahuel J, Grutter MG, Cohen NC,Rasetti V, et al. Structure-based design of aliskiren, a novelorally effective renin inhibitor. Biochem Biophys ResCommun 2003;308:698-705.5. Campbell DJ. Interpretation of plasma renin concentrationin patients receiving aliskiren therapy. Hypertension2008;51:15-8.6. Nussberger J, Wuerzner G, Jensen C, Brunner HR.Angiotensin II suppression in humans by the orally activerenin inhibitor aliskiren (SPP100): comparison with enalapril.Hypertension 2002;39:E1-8.7. Waldmeier F, Glaenzel U, Wirz B, Oberer L, Schmid D,Seiberling M, et al. Absorption, distribution, metabolism,and elimination of the direct renin inhibitor aliskiren inhealthy volunteers. Drug Metab Dispos 2007;35:1418-28.Dr Campbell holds a Senior Research Fellowship from theNational Health and Medical Research Council (NHMRC), andhas received research grants from the NHMRC and the NationalHeart Foundation. He has had research contracts with Solvay andNovartis and has been on an advisory board for Novartis.Self-test questionsThe following statements are either true or false(answers on page 143)5. Renin inhibitors act at angiotensin II receptors.6. Renin inhibitors increase the plasma concentrationof renin.Experimental and clinical pharmacologyClinical implications of renin inhibitorsKaren Duggan, Chair, National Blood Pressure and Vascular Disease Advisory Committee, andformerly Director, Hypertension Service, Sydney South West Area Health ServiceSummaryDirect renin inhibition lowers blood pressure byan effective blockade of the renin-angiotensinsystem. Aliskiren is the first renin inhibitor to bemarketed for the treatment of hypertension. Atcurrently available doses it lowers blood pressureto a similar degree as other antihypertensive drugs.Used in combination with thiazides, angiotensinconverting enzyme inhibitors, angiotensin receptorantagonists or calcium channel blockers, aliskirenhas improved blood pressure control with noappreciable increase in adverse events. Aliskirenhas an adverse effect profile comparable toplacebo, but its long-term effects are unknown.Key words: aliskiren, antihypertensives, hypertension.(Aust Prescr 2009;32:135–8)IntroductionHypertension is one of the commonest reasons for generalpractitioner attendances. Less than 25% of those who arediagnosed attain their recommended blood pressure targets,while some studies place this figure as low as 7%. Althoughmuch of this failure to control blood pressure can be attributedto therapeutic inertia, the adverse effects of antihypertensivedrugs also contribute. These adverse effects often limit the dosesat which antihypertensive drugs can be used. This problem hasprompted the ongoing search for more efficacious drugs withfewer adverse effects. One such group of drugs is the directrenin inhibitors which are currently undergoing clinical trials.The first of the drugs to be marketed is aliskiren.Prorenin and the renin receptorThe discovery of the renin receptor provided a new rolefor renin, that of a profibrotic agent in its own right. It wassubsequently found that the renin receptor also bindswww.australianprescriber.com| Volume 32 | NUMBER 5 | OCTOBER 2009 135