Endothelin receptor antagonists are mainstays in PAH treatment, with drug selection currently driven by safety profiles and pharmacokinetic interactions rather than receptor selectivity.
When selecting an endothelin receptor antagonist for PAH, safety profiles and drug interactions are currently more clinically relevant than the drug's receptor selectivity.
The endothelin (ET) system, especially ET-1 and the ET(A) and ET(B) receptors, has been implicated in the pathogenesis of pulmonary arterial hypertension (PAH). Together with prostanoids and phosphodiesterase 5 inhibitors, ET receptor antagonists have become mainstays in the current treatment of PAH. Three substances are currently available for the treatment of PAH. One of these substances, bosentan, blocks both ET(A) and ET(B) receptors, whereas the two other compounds, sitaxsentan and ambrisentan, are more selective blockers of the ET(A) receptor. There is ongoing debate as to whether selective or nonselective ET receptor blockade is advantageous in the setting of PAH, although there is no clear evidence that receptor selectivity is relevant with regard to the clinical effects of these drugs. For the time being, other features, such as safety profiles and the potential for pharmacokinetic interactions with other drugs used in the treatment of PAH, may be more important than selectivity or nonselectivity when selecting treatments for individual patients.
Dupuis et al. (Thu,) conducted a review in Pulmonary arterial hypertension. Endothelin receptor antagonists (bosentan, sitaxsentan, ambrisentan) was evaluated. Endothelin receptor antagonists are mainstays in PAH treatment, with drug selection currently driven by safety profiles and pharmacokinetic interactions rather than receptor selectivity.