should be exercised when aliskiren is administered with ketoconazole or other moderate P-glycoprotein inhibitors (itraconazole, clarithromycin, telithromycin, erythromycin, or amiodarone). Recommendations have been made to stop prescribing aliskiren-containing medicines to patients with diabetes (type 1 or type 2) or with moderate to severe kidney impairment who are also taking an ACE inhibitor or ARB. Such patients should consider alternative antihypertensive treatment as necessary. Mechanism of action Aliskiren is an antagonist to renin. Renin, the first enzyme in the renin–angiotensin–aldosterone system, plays a role in blood pressure control. It cleaves angiotensinogen to angiotensin I, which is in turn converted by angiotensin-converting enzyme (ACE) to angiotensin II. Angiotensin II has both direct and indirect effects on blood pressure. It directly causes arterial smooth muscle to contract, leading to vasoconstriction and increased blood pressure. Angiotensin II also stimulates the production of aldosterone from the adrenal cortex, which causes the tubules of the kidneys to increase reabsorption of sodium, with water following, thereby increasing plasma volume, and thus blood pressure. Aliskiren binds to the S3bp binding site of renin, essential for its activity. Binding to this pocket prevents the conversion of angiotensinogen to angiotensin I. Aliskiren is also available as combination therapy with hydrochlorothiazide. Chemistry The chemical name for aliskiren is (2 S,4S,5S,7S)-5-amino-N-(2-carbamoyl-2-methylpropyl)-4-hydroxy-2-isopropyl-7-[ 4-methoxy-3-(3-methoxypropoxy)benzyl]-8-methylnonanamide. Rationale for design Many drugs control blood pressure by interfering with angiotensin or aldosterone. However, when these drugs are used chronically, the body increases renin production, which drives blood pressure up again. Therefore, pharmacologists have been looking for a drug to inhibit renin directly. Aliskiren is the first drug to do so. References External links Renin inhibitors Catechol ethers Novartis brands