Oral renin inhibitors

@article{Staessen2006OralRI,
  title={Oral renin inhibitors},
  author={Jan A. Staessen and Yan Li and Tom Richart},
  journal={The Lancet},
  year={2006},
  volume={368},
  pages={1449-1456}
}
Use of drugs that inhibit the renin-angiotensin system is an effective way to intervene in the pathogenesis of cardiovascular and renal disorders. The idea of blocking the renin system at its origin by inhibition of renin has existed for more than 30 years. Renin inhibition suppresses the generation of the active peptide angiotensin II. The first generation of orally active renin inhibitors were never used clinically because of low bioavailability and weak blood-pressure-lowering activity. At… Expand

Paper Mentions

Interventional Clinical Trial
The proportion of hypertensive patients achieving adequate blood pressure control meeting guideline targets remains low. Of those patients on blood pressure lowering drugs, only 50… Expand
ConditionsHypertension
InterventionDevice
Interventional Clinical Trial
Antihypertensive drug treatment is effective in only about 50% of patients. One mechanism responsible for treatment failure is a drug related stimulation of the renin… Expand
ConditionsHypertension
InterventionDrug
Renin inhibitor in hypertension treatment: from pharmacological point of view
TLDR
Aliskiren becomes the first renin inhibitor with indications for the treatment of hypertension in Indonesia, a compounds with improved oral bioavailability, specificity and efficacy, with a focus on aliskiren. Expand
Aliskiren – an orally active renin inhibitor. Review of pharmacology, pharmacodynamics, kinetics, and clinical potential in the treatment of hypertension
TLDR
Aliskiren is the first in a new class of orally active, non-peptide, low molecular weight renin inhibitors, and so far the only renin inhibitor that has progressed to phase III clinical trials. Expand
Direct Inhibition of Renin as a Cardiovascular Pharmacotherapy: Focus on Aliskiren
TLDR
Studies in marmosets and rats demonstrated that aliskiren reduced blood pressure in a dose-dependent manner and is highly efficacious in blocking plasma renin activity with parallel reductions in the levels of the other downstream constituents of the renin-angiotensin system. Expand
Renin inhibition: A new modality for hypertension management
  • H. Siragy
  • Medicine
  • Current hypertension reports
  • 2007
TLDR
Using RAS inhibitors does not totally prevent Ang II formation, which could continue to contribute to development of end-organ damage, and studies are in progress to evaluate the potential role for renin inhibition in management of kidney and cardiac diseases. Expand
Aliskiren: A novel, orally active renin inhibitor
TLDR
The present review mainly focuses on the pharmacodynamics and pharmacokinetics and clinical aspects of aliskiren, the first member of the new class of orally active direct renin inhibitors recently approved by the US Food and Drug Administration for the treatment of hypertension. Expand
Renin inhibition in hypertension.
TLDR
Aliskiren is a potent, low-molecular-weight, nonpeptide, direct renin inhibitor with sufficient bioavailability to produce sustained suppression of plasma renin activity after oral administration, and when given with an angiotensin receptor blocker, aliskiren produces significant additional BP reduction indicative of complimentary pharmacology and more complete renin-angiotens in system blockade. Expand
Novel Drugs Targeting Hypertension: Renin Inhibitors
  • A. Danser
  • Medicine
  • Journal of cardiovascular pharmacology
  • 2007
TLDR
The potential differences between renin inhibitors and the currently existing blockers of the renin-angiotensin system (RAS) are summarized, taking also into consideration the recently discovered (pro)renin receptor. Expand
Aliskiren, the future of renin–angiotensin system blockade?
TLDR
Aliskiren has been recently shown to be efficacious in hypertensive patients at once-daily oral dosing with favorable pharmacokinetics and the potential to improve end-organ protection. Expand
Aliskiren, the first in a new class of direct renin inhibitors for hypertension: present and future perspectives
  • B. Oh
  • Medicine
  • Expert opinion on pharmacotherapy
  • 2007
TLDR
The role of aliskiren in the therapeutic management of hypertension is defined and possible synergistic potential when combined with a thiazide diuretic, ACE inhibitor, angiotensin receptor blocker and calcium channel blocker both in terms of efficacy and tolerability is defined. Expand
Oral direct renin inhibition: premise, promise, and potential limitations of a new antihypertensive drug.
TLDR
The premise, promise, and potential limitations of this new class of renin-angiotensin system inhibitor, aliskiren, recently received approval for the treatment of hypertension are addressed. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 80 REFERENCES
Clinical Pharmacokinetics and Efficacy of Renin Inhibitors
TLDR
After 1 week of oral treatment with the renin inhibitor remikiren, the antihypertensive effect was reduced in salt-repleted hypertensive patients and subsequent intravenous administration of the drug did not further affect blood pressure, indicating that it was not the first pass effect that was limiting the efficacy of Remikiren. Expand
Pharmacology of renin inhibitors and their application to the treatment of hypertension.
TLDR
Studies in animal models and preliminary studies in humans indicate that renin inhibitors have the same therapeutic potential as angiotensin-converting enzyme inhibitors, but inhibitors with better oral bioavailability and a long duration of action are needed to assess their full therapeutic potential. Expand
Renin inhibitors as novel treatments for cardiovascular disease
The renin–angiotensin system (RAS) plays an important role in the development of cardiovascular diseases such as hypertension and heart failure. Inhibitors of renin (EC 3.4.99.19) block the RAS atExpand
Structure-based design of aliskiren, a novel orally effective renin inhibitor.
TLDR
Aliskiren is the first in a novel class of renin inhibitors with the potential for treatment of hypertension and related cardiovascular diseases and employs a combination of molecular modelling and crystallographic structure analysis to design renin inhibitor lacking the extended peptide-like backbone of earlier inhibitors. Expand
Renal vascular responses to renin inhibition with zankiren in men
TLDR
Renin inhibition exerts a remarkable renal vasodilator action, perhaps reflecting the lipophilicity of the agents developed to date, an action that may have clinical implications for the prevention of renal injury in patients at risk. Expand
Angiotensin II Suppression in Humans by the Orally Active Renin Inhibitor Aliskiren (SPP100): Comparison With Enalapril
TLDR
Aliskiren has the potential to become the first orally active renin inhibitor that provides a true alternative to ACE-inhibitors and Ang II receptor antagonists in therapy for hypertension and other cardiovascular and renal diseases. Expand
Renin inhibitors: An antihypertensive strategy on the verge of reality
TLDR
It is likely that the first renin inhibitors will be available within the next 3 years and many of the obstacles associated with the development of early renin inhibitor have been overcome. Expand
Blood Pressure Lowering in Essential Hypertension With an Oral Renin Inhibitor, Aliskiren
TLDR
It is demonstrated that aliskiren, through inhibition of renin, is an effective and safe orally active BP-lowering agent and well tolerated at all doses studied. Expand
Design of specific inhibitors of angiotensin-converting enzyme: new class of orally active antihypertensive agents.
TLDR
A hypothetical model of the active site of angiotensin-converting enzyme, based on known chemical and kinetic properties of the enzyme, has enabled a new class of potent and specific inhibitors, carboxyalkanoyl and mercaptoalkanoysl derivatives of proline, to be designed. Expand
Nonparallel effects of renin inhibitor treatment on plasma renin activity and angiotensins I and II in hypertensive subjects. An assay-related artifact.
TLDR
This study addresses the possibility that renin inhibitors may show a high degree of plasma protein binding in vivo and that displacement of protein-bound inhibitor during the assay of PRA in vitro may lead to overestimation of renin inhibition. Expand
...
1
2
3
4
5
...