Aliskiren
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sheng Shi, M.D. [2]
For patient information about Aliskiren, click here. Synonyms / Brand Names: TEKTURNA®
Overview
Aliskiren (INN) is a first in class renin inhibitor co-developed by the Swiss pharmaceutical companies Novartis and Speedel.[1][2] It was approved by the U.S. Food and Drug Administration in 2007 for the treatment of hypertension.[3] The trade name for aliskiren is Tekturna in the USA, and Rasilez in the UK.
Category
Renin inhibitors;Phenol ethers;Cardiovascular Drugs
FDA Package Insert
TEKTURNA (aliskiren hemifumarate) tablet, film coated
Indications and Usage | Dosage and Administration | Dosage Forms and Strengths | Contraindications | Warnings and Precautions | Adverse Reactions | Drug Interactions | Use in Specific Populations | Overdosage | Description | Clinical Pharmacology | Nonclinical Toxicology | Clinical Studies | How Supplied/Storage and Handling | Patient Counseling Information | Labels and Packages
Mechanism of Action
Reninis secreted by the kidney in response to decreases in blood volume and renal perfusion. Renincleaves angiotensinogen to form the inactive decapeptide angiotensin I (Ang I). Ang I is converted to the active octapeptide angiotensin II (Ang II) by angiotensin-converting enzyme (ACE) and non-ACE pathways. Ang II is a powerful vasoconstrictor and leads to the release of catecholamines from the adrenal medulla and prejunctional nerve endings. It also promotes aldosterone secretion and sodium reabsorption. Together, these effects increase blood pressure. Ang II also inhibits Reninrelease, thus providing a negative feedback to the system. This cycle, from Reninthrough angiotensin to aldosterone and its associated negative feedback loop, is known as the renin-angiotensin-aldosterone system (RAAS). Aliskiren is a direct Renininhibitor, decreasing plasma Reninactivity (PRA) and inhibiting the conversion of angiotensinogen to Ang I. Whether aliskiren affects other RAAS components, e.g., ACE or non-ACE pathways, is not known.
All agents that inhibit the RAAS, including Renininhibitors, suppress the negative feedback loop, leading to a compensatory rise in plasma Reninconcentration. When this rise occurs during treatment with ACE inhibitors and ARBs, the result is increased levels of PRA. During treatment with aliskiren, however, the effect of increased Reninlevels is blocked so that PRA, Ang I and Ang II are all reduced, whether aliskiren is used as monotherapy or in combination with other antihypertensive agents.
References
- ↑ Gradman A, Schmieder R, Lins R, Nussberger J, Chiang Y, Bedigian M (2005). "Aliskiren, a novel orally effective renin inhibitor, provides dose-dependent antihypertensive efficacy and placebo-like tolerability in hypertensive patients". Circulation. 111 (8): 1012–8. PMID 15723979.
- ↑ Straessen JA, Li Y, and Richart T (2006). "Oral Renin Inhibitors". Lancet. 368 (9545): 1449–56. PMID 17055947.
- ↑ "First Hypertension Drug to Inhibit Kidney Enzyme Approved". CBC. March 6, 2007.