How Do PAH Endothelin Antagonists Work?

PAH endothelin antagonists are medications used to treat pulmonary arterial hypertension (PAH), a condition of high blood pressure in the arteries that carry deoxygenated blood from the heart to the lungs. Endothelin antagonists reduce pulmonary hypertension by preventing constriction of the pulmonary arteries.

Endothelin-1 is a natural substance secreted by cells in the inner layer (endothelium) of blood vessels. Endothelin-1 causes vasoconstriction and induces proliferation of vascular smooth muscle cells by binding to ET-A and ET-B receptors, two types of protein molecules on vascular endothelial and smooth muscle cells.

Endothelin antagonists either selectively bind to ET-A or both ET-A and ET-B receptors and prevent endothelin-1 from activating them. Endothelin antagonists primarily dilate the pulmonary arteries and have little effect on systemic blood pressure because endothelin receptors are concentrated mainly in pulmonary blood vessels.

PAH endothelin antagonists are oral tablets prescribed for the treatment of the following conditions:

FDA-approved:

• Pulmonary arterial hypertension: To improve exercise ability and slow down the progression of disease in patients with:
  • Idiopathic PAH
  • Congenital PAH
  • PAH caused by connective tissue diseases
  • PAH associated with congenital heart disease 

Orphan designation:

• Idiopathic pulmonary fibrosis (scar tissue formation)
• Systemic sclerosis (autoimmune connective tissue disease)
• Fontan-palliated patients (Fontan palliation is a type of surgical procedure performed for a congenital heart condition)
• Chronic thromboembolic pulmonary hypertension (CTEPH)

Side effects of PAH endothelin antagonists may include the following:

• Decrease in hemoglobin (Hgb)
• Respiratory tract infection
• Peripheral edema
• Headache
• Nasopharyngitis (inflammation of nose and throat)
• Bronchitis (inflammation of bronchial passage)
• Anemia
• Flushing
• Hypotension (low blood pressure)
• Urinary tract infection
• Influenza
• Nasal congestion
• Sinusitis (inflammation of the sinuses)
• Palpitations
• Chest pain
• Syncope (fainting)
• Dyspnea (shortness of breath)
• Abnormal/elevated liver enzymes ALT and AST
• Jaundice
• Hepatotoxicity (toxicity to the liver)
• Unexplained hepatic cirrhosis
• Liver failure
• Arthralgia (joint pain)
• Constipation
• Abdominal pain
• Dizziness
• Fatigue
• Fluid retention
• Heart failure associated with fluid retention
• Symptomatic hypotension
• Nausea
• Vomiting
• Hypersensitivity reactions such as:
  • Rash
  • Pruritus (itching)
  • Angioedema (swelling in the tissue under the skin or mucous membranes)
  • Drug rash with eosinophilia and systemic symptoms (DRESS)
  • Anaphylaxis (severe allergic reaction)
• Thrombocytopenia (low platelet count in the blood)
• Neutropenia (low blood count of neutrophils)
• Leukopenia (low blood count of leukocytes)

Information contained herein is not intended to cover all possible side effects, precautions, warnings, drug interactions, allergic reactions, or adverse effects. Check with your doctor or pharmacist to make sure these drugs do not cause any harm when you take them along with other medicines. Never stop taking your medication and never change your dose or frequency without consulting your doctor.

Generic and brand names of PAH endothelin antagonist drugs include:

• ambrisentan
• bosentan
• Letairis
• macitentan
• Opsumit
• Tracleer