What is MICARDIS^®?

MICARDIS^® is an angiotensin II receptor blocker, also known as an ARB. These drugs interrupt the renin–angiotensin system (RAS) cascade, but unlike the angiotensin converting enzyme (ACE) inhibitors, they act on a more specific step in the cascade and prevent angiotensin II from binding to its receptors.

Angiotensin II is a vasopressor interacting with one of two angiotensin II receptors: angiotensin II Type 1 (AT₁) and Type 2 (AT₂). AT₁ mediates all the known actions of angiotensin II on blood pressure control.¹ MICARDIS^® provides site-specific blockade of the AT₁ receptor² and complete blockade of the harmful AT₁ receptor-mediated angiotensin II effects.

Harmful effects of AT₁ stimulation blocked by MICARDIS^®

• Vasoconstriction
• Sodium retention
• Sympathetic nervous system activation
• Inflammation
• Growth-promoting effects
• Increase in aldosterone
• Apoptosis

MICARDIS^® provides selective, long-term AT₁ receptor blockade

The receptor binding profile of an ARB has important clinical implications. MICARDIS^® has a very high binding affinity for the AT₁ receptor and its slow dissociation from the receptor contributes to the long-lasting, 24-hour effect of MICARDIS^®.³

Importantly, MICARDIS^® displays no binding affinity to the AT₂ receptor, which is thought to have beneficial effects in the cardiovascular system.⁴

MICARDIS^® shows insurmountable, but reversible receptor blockade

MICARDIS^® provides specific AT₁ blockade that is also said to be insurmountable.⁵ An ARB is said to show insurmountable blockade if increasingly higher concentrations of angiotensin II are unable to overcome the receptor blockade.^6,7 The insurmountable nature of MICARDIS^® binding is likely to result from the slow dissociation from the AT₁ receptor shown in animal studies.⁵

ARBs have a distinct mechanism of action from ACE inhibitors

ACE inhibitors block the RAS at the enzymatic level, while ARBs, such as MICARDIS^®, specifically inhibit the RAS at the receptor site. This difference has important implications in the treatment of hypertension, as specifically targeting the AT₁ receptor has no effect on bradykinin metabolism or other receptor systems.²

In contrast to ARBs, ACE inhibitors are non-specific in their effects. By blocking the action of ACE, they not only stop production of angiotensin II from angiotensin I, but also the catabolism of other biologically important peptides, including bradykinin and substance P. Elevations in these peptides are probably responsible for the occurrence of dry, persistent cough, a troublesome side-effect associated with ACE inhibitor therapy.^8,9

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