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Aliskiren volume of distribution
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What is Aliskiren
Aliskiren is the first in a class of drugs called direct renin inhibitors. Its current licensed indication is essential (primary) hypertension. While used for high blood pressure, other better studied medications are typically recommended due to concerns of higher side effects and less evidence of benefit. In December 2011, Novartis halted a clinical trial of the drug after discovering increased incidence of nonfatal stroke, kidney complications, high blood potassium, and low blood pressure in people with diabetes and kidney impairment.
Aliskiren mechanism of action
Renin is secreted by the kidney in response to decreases in blood volume and renal perfusion. Renin cleaves angiotensinogen to form the inactive decapeptide angiotensin I (Ang I). Ang I is converted to the active octapeptide angiotensin II (Ang II) by 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 renin release, thus providing a negative feedback to the system. This cycle, from renin through angiotensin to aldosterone and its associated negative feedback loop, is known as the renin angiotensin aldosterone system (RAAS). Aliskiren is a direct renin inhibitor, decreasing plasma renin activity (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 renin inhibitors, suppress the negative feedback loop, leading to a compensatory rise in plasma renin concentration. When this rise occurs during treatment with ACEIs and ARBs, the result is increased levels of PRA. During treatment with aliskiren, however, the effect of increased renin levels 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.
Dosage forms of Aliskiren
Novartis Pharmaceuticals Corporation
Humans and other mammals
Indication of Aliskiren
For the treatment of hypertension, to lower blood pressure.
Toxicity of Aliskiren
The most likely manifestation of overdosage would be hypotension.
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