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Valsafors
First Russian make of Valsatran, which is effective in blood pressure reduction, extension of life expectancy and improvement of life quality of the patients with arterial hypertension.
 Valsatran is an effective and safe antihypertensive product which has been used in clinical practice for a good few years. The only thing that impedes a wider use of Angiotensin II blockers is their higher price compared to other antihypertensive products. Russian medical staff got a chance of wider indications of this promising drug product since pharmacies began selling high quality Valsatran of domestic make (Valsaforce ®), which is much more affordable than the original product.
S.V. Moiseev, Professor of the therapeutic and professional diseases division of I.M. Sechenov Medical Academy, M.V. Lomonosov Moscow State University.
Mechanism of action
 The crucial role in the progress of an arterial hypertensia (AH) belongs to the activation of renin-angiotensin-aldosteron system (RAAS) (see Figure).
Renin is an enzyme that originates in kidneys; it affects hypertensinogen, resulting in formation of angiotensin I. By itself, Angiotensin I can only initiate insignificant angiospasms. However activation of angiotensin I through angiotensin-converting enzyme (ACE) leads to formation of angiotensin II, a potent vasoconstrictor. Besides, Angiotensin II increases secretion of Aldosterone, which also supports a rise in arterial pressure as it detains sodium and water in the body. RAAS activity can be reduced by inhibition of ACE, blocking formation of Angiotensin II from Angiotensin I. Mechanism of action and pharmacological effects of АТ1-angiotensive receptors blockers.
Antihypertensive action and other pharmacological effects of АТ1- angiotensive receptors blockers are based on direct and indirect mechanisms. The direct mechanism refers to direct attenuation of Angiotensin II effects as a result of АТ1-receptors block. The indirect mechanism is determined by additional stimulation of АТ2-receptors which enhances their protective action on kidneys, heart, and vessels.
АТ1-Angiotensin Receptors Blockers
A new approach to suppression of excessive RAAS activity in bloodstream and tissues of patients presenting with hypertension is related to the use of a different class of ACE inhibitors, a class of cardiovascular preparations that is known as Angiotensin II antagonists, or АТ1-angiotensin receptors blockers.
Similarly to the ACE inhibitors, АТ1-angiotensin receptors blockers cause peripheral vasodilatation and suppress excessive activation RAAS in bloodstream and tissues of those with arterial hypertension and chronic cardiac insufficiency.
АТ1-angiotensin receptors blockers have certain virtues compared to ACE inhibitors:
1. They are more effective in suppressing cardiovascular effects of RAAS activation.
2. They have better specificity of action.
3. They are more tolerable.
Cardioprotective Action
Similar to other antihypertensive preparations, АТ1-angiotensin receptors blockers induce regression of the left ventricle hypertrophy and by doing so they can improve life expectancy of hypertension patients. Effects of АТ1-blockers on left ventricle hypertrophy are comparable to that of ACE inhibitors.
Regression of the left ventricle hypertrophy through treatment is determined not only by a decrease in system arterial pressure, but also by a direct antiproliferative action of the blockers.
Vasoprotective Action
The mechanisms of AT1-angiotensin receptors blockers vasoprotective effects are related to their antihypertensive, antifibrotic, antithrombotic, antioxidative and anti-inflammatory action.
Renoprotective Action
Kidneys play an important role in arterial tension increase in those suffering from hypertension, diabetes mellitus and not-diabetic kidney disorders. Arterial hypertension, in turn, is one of the major factors that contribute to a progression of renal disorders in hypertension patients and in particular in those affected by diabetic nephropathy and other renal disorders.
Many, if not all, of Angiotensin’s II adverse effects on the structure and function of kidneys are mediated by АТ1-angiotensin receptors. This gives reasons to assume that АТ1-angiotensin receptors blockers, as well as ACE inhibitors, have a renoprotective effect. The difference in mechanisms of nephritic effects of АТ1-blockers and ACE inhibitors is that the former do not have any direct influence on bradykinin metabolism, and indirectly stimulate АТ2- angiotensin receptors, which mediate a dilation of renal arterioles.
Valsartan
The difference between Valsartan and Lozartan and other АТ1-angiotensin receptors blockers is that in its chemical structure it is not a heterocyclic compound.
Valsartan is a high-selective АТ1-angiotensin receptors blocker. It is more selective, than Lozartan: while with Lozartan its affinity to AT1-receptor is 3000 times higher than that to АТ2-receptors, with Valsartan this indicator is still 10 times higher. Valsartan acts as a noncompetitive antagonist of Angiotensin II for АТ1-angiotensin receptors. Unlike Lozartan, an overage of Angiotensin II cannot displace Valsartan from its bond with the AT1-receptor.
Valsartan as such shows a pharmacological activity; unlike Lozartan it does not have active metabolites.
Valsartan’s half life in plasma is on the average about 9 hours, which is longer than that of Lozartan. Valsartan is primarily eliminated from the body with bile and faeces (70-86%) mostly unchanged. Only 14-30% of Valsartan is eliminated through kidneys, which makes its administration to patients presenting with renal insufficiency safe.
Valsatran does not influence pharmacokinetics and pharmacodynamics of digoxin, hydrochlorothiazide, furosemide, amlodipine, warfarin, glibenclamide, and indomethacin. Valsartan’s metabolism does not involve cytochrome P-450 isoenzymes, therefore neither inhibitors, nor inductors of these isoenzymes influence its pharmacokinetics.
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