aliskiren and Hypotension

Angiotensin (Ang) II plays important roles in the development of hypertension and cardiovascular and renal injury. Pharmaceutical approaches to block its activity led to the development of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. Numerous trials have documented their efficacy in controlling blood pressure, minimising left ventricular remodelling, preventing progression to heart failure, ameliorating proteinuria and retarding renal disease progression. Although they are considered safe in general, there remain concerns about the potential for adverse events in certain target populations. Recently, several novel, low molecular weight renin inhibitors without the extended peptide-like backbone of previous renin inhibitors were developed with favourable pharmacokinetic properties. They have been shown to successfully reduce Ang II levels in normal volunteers and to lower blood pressure in patients with mild-to-moderate hypertension. In this review, the authors summarise current knowledge about these renin inhibitors.

Topics: Abnormalities, Drug-Induced; Amides; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Clinical Trials as Topic; Fumarates; Humans; Hyperkalemia; Hypertension; Hypotension; Inappropriate ADH Syndrome; Male; Mice; Renin

Hypotension and syncopal attacks have been reported in association with drugs which block the renin-angiotensin-aldosterone system (RAAS). It has been proposed that the underlying mechanism is due to sensitisation of the Bezold-Jarisch reflex leading to withdrawal of sympathetic tone, profound and prolonged bradycardia, and hypotension. Sensitisation of this reflex occurs in the presence of blockade of the RAAS. In the ALTITUDE trial the use of the direct renin inhibitor, aliskiren, was associated with hypotensive episodes and an excess of ischaemic stroke. It is hypothesised that this is best explained by activation of the Bezold-Jarisch reflex, which may be particularly important in circumstances where there is dual blockade of the RAAS.

Topics: Amides; Brain Ischemia; Clinical Trials as Topic; Fumarates; Humans; Hypotension; Reflex; Renin-Angiotensin System; Risk Factors; Stroke

Topics: Amides; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Consumer Advocacy; Drug Labeling; Drug Therapy, Combination; Fumarates; Humans; Hypertension; Hypotension; Kidney; Randomized Controlled Trials as Topic; Renin; United States; United States Food and Drug Administration

Topics: Amides; Antihypertensive Agents; Blood Pressure; Child; Follow-Up Studies; Fumarates; Humans; Hypotension; Male; Medication Errors; Time Factors