Endothelin receptor antagonists

Endothelin receptor antagonists

Bosentan (Tracleer®), sitaxentan (Thelin®) and ambrisentan (Volibris®) are all competitive endothelin receptor antagonists. By blocking the ET receptor, increased levels of endothelin-1 cannot have their vasoconstricting effects.

The nonselective endothelin receptor antagonist bosentanimproves symptoms and exercise tolerance. Sitaxentan and ambrisentan are ETA selective endothelin receptor antagonists, which should in theory produce less adverse effects.

The most common adverse effects

of these antagonists are headache, nasopharyngitis, flushing, hypotension and peripheral edema in the legs. Because of the high frequency of abnormal hepatic function tests associated with drug use, primarily an increase in transaminases, it is recommended that liver function be monitored monthly throughout the duration of use. This phenomenon is dose dependent.

It is important to note, that both sitaxentan and bosentan are CYP P450 inducers and enhance the effect of several drugs including anticoagulants.

EPARs of bosentan, sitaxentan and ambrisentan.