Pulmonary Arterial Hypertension (PAH): Types of Medicines

Key Facts:

• Pulmonary arterial hypertension (PAH) is an uncommon and progressive condition that typically worsens over time, often with no identifiable cause.
• The disorder predominantly affects women aged 30 to 60, making them the most at-risk demographic.
• Treatments of PAH are available to control symptoms and improve quality of life (QoL).
• PAH is classified as Group 1 pulmonary hypertension within the five main categories of this disease, distinguishing it from other types based on its specific characteristics.

The exact cause of pulmonary arterial hypertension (PAH) remains unclear. Unlike other types of pulmonary hypertension, where high blood pressure in the lungs is secondary to heart or lung conditions, PAH develops as a distinct blood vessel disease. Researchers suspect that it begins with damage to the cells lining the lung’s blood vessels, leading to progressive narrowing and remodeling of these vessels. When the underlying cause of this cellular damage is unknown, it is classified as idiopathic PAH. If a genetic mutation is identified as the cause, it is referred to as heritable PAH, which accounts for 15-20% of cases.
Certain conditions and factors have been linked to the development of PAH, including connective tissue diseases like lupus and scleroderma, exposure to drugs and toxins such as methamphetamine and cocaine, infections like HIV and schistosomiasis, liver cirrhosis, and congenital heart defects.

Who Is at Risk?

Pulmonary arterial hypertension (PAH) occurs more commonly in women aged 30 to 60, with African American and Hispanic women being disproportionately affected. Additionally, the presence of an inherited form of PAH means that having a family history of the condition may increase your risk.

Symptoms of Pulmonary Arterial Hypertension:

In the early stages of pulmonary arterial hypertension (PAH), symptoms may be subtle or entirely absent. As the condition advances, signs become more noticeable, often mimicking those of other lung diseases. Common symptoms include:

• Shortness of breath, particularly during physical activity
• Persistent fatigue
• Swelling in the feet, legs, abdomen, or neck (edema)
• Episodes of dizziness or fainting
• Chest discomfort or pain
• Racing or pounding heartbeats (palpitations)
• Bluish discoloration of lips and fingers (cyanosis)
• A persistent cough
• A hoarse voice
• These symptoms highlight the importance of early detection and management of PAH.

How Pulmonary Arterial Hypertension Is Diagnosed?
Diagnosing pulmonary arterial hypertension (PAH) is challenging due to its similarity to other lung diseases. It requires ruling out other conditions through several tests conducted by pulmonologists and cardiologists, including:

• Blood Tests: Check for conditions like autoimmune diseases, liver issues, and thyroid problems.
• Electrocardiogram (ECG): Identifies heart abnormalities or strain on the right side of the heart.
• Lung Function Tests: Screens for diseases such as asthma or COPD.
• 6-Minute Walk Test: Measures exercise capacity and oxygen levels.
• Echocardiogram: Assesses heart structure and pulmonary artery pressure.
• Right Heart Catheterization: An invasive procedure to measure lung blood pressure, done if other tests are inconclusive.

Diagnosing Heritable PAH (HPAH):
Diagnosis involves ruling out other potential causes, identifying mutations in genes linked to HPAH, and confirming the presence of PAH in one or more family members.

Delayed Diagnosis:
Pulmonary arterial hypertension (PAH) is often challenging to diagnose, leading to delays of two years or more in many cases. Several factors contribute to this delay:

• Non-Specific Early Symptoms: The initial signs of PAH are typically mild and lack specificity, making them easy to overlook.
• Misdiagnosis: As symptoms worsen, they can resemble those of more common conditions like asthma or congestive heart failure, leading to incorrect diagnoses.
• Patient Profile: Younger individuals and those with pre-existing respiratory conditions are particularly prone to delayed recognition of the disease.

Treatment and Management of PAH:
Medications and treatments for pulmonary arterial hypertension (PAH) can slow disease progression and improve quality of life. Early diagnosis is linked to better outcomes, enabling timely treatment. PAH therapies include oral, inhaled, and injectable options that help improve blood flow, support heart and lung function, and target imbalances in nitric oxide, endothelin, or prostacyclin pathways. While no test identifies specific imbalances, these treatments work to slow disease progression. Collaborate with your healthcare provider to determine the best treatment plan for your needs.

Nitric Oxides: Nitric oxides play a crucial role in maintaining healthy blood flow by relaxing and dilating blood vessels, ensuring proper circulation throughout the body.
Phosphodiesterase Inhibitors (PDE5 Inhibitors):

Common Medications: Tadalafil, Sildenafil

• How It Works: These medications relax the lungs and widen blood vessels, reducing the strain on the heart and improving blood circulation. This mechanism helps the heart pump blood more efficiently.
• Side Effects: Users may experience headaches, flushing, dizziness, nausea, nasal congestion, muscle pain, or back discomfort.
• Administration: Available as oral tablets or subcutaneous injections (short-term use only).
  Benefits: These inhibitors slow disease progression, enhance physical activity tolerance, and improve overall quality of life.

Soluble Guanylate Cyclase Stimulators (SGCS):
Medication Names: Adempas, Riociguat

• What It Does: It works by relaxing the blood vessels in the lungs, improving blood flow and helping the heart pump blood more efficiently.
• Common Side Effects: Some people may experience headaches, indigestion, gastritis, dizziness, low blood pressure, anemia, GERD, constipation, or bleeding.
• Delivery Method: It is taken orally.
• Additional Information: Adempas helps slow the progression of the disease and enhances physical activity levels, allowing individuals to engage in more daily activities.

Endothelin Receptor Antagonists (ERAs): ERAs prevent blood vessels from narrowing
Endothelin Receptor Antagonists (ERAs):

• Medications Included: Bosentan, Ambrisentan, Macitentan
• How It Works: ERAs help lower pulmonary blood pressure, making it easier for the heart to pump blood, and improving overall heart function.
• Common Side Effects: These medications may cause headaches, joint pain, low blood pressure, dizziness, flushing, irregular heart rhythms, and cold-like symptoms.
• Administration: Taken orally in pill form.
• Key Benefits: ERAs can enhance exercise tolerance, slow the progression of diseases like pulmonary hypertension, and relieve symptoms associated with poor blood flow.

Prostaglandins / Prostacyclins: It helps blood vessels stay open
Prostacyclin Analogue:

• Medication Names: Epoprostenol, Flolan, Veletri, Treprostinil, Treprostinil Inhaled, Iloprost, Orenitram, Remodulin, Tyvaso, Ventavis
• What It Does: These medications help blood vessels in the lungs relax, improving circulation and reducing shortness of breath, especially during physical activity.
• Common Side Effects: Patients may experience flushing, headache, muscle pain, coughing, diarrhea, nausea, vomiting, indigestion, sore throat, flu-like symptoms, or a rash.
• Delivery Method: Prostacyclin analogs can be delivered orally, inhaled, or via intravenous (IV) or subcutaneous injection, depending on the specific treatment.
• Additional Information: Inhaled treatments, in particular, can improve exercise tolerance and overall physical performance by reducing breathlessness.

Selective IP Receptor Agonist:

• Medication Name: Selexipag
• Function: Helps relax blood vessels in the lungs to improve blood flow.
• Typical Side Effects: Headache, joint pain, jaw discomfort, muscle aches, flushing, skin rash, anemia, nausea, and injection site reactions (if administered subcutaneously).
• Administration: Available as oral tablets or via subcutaneous injection.
• Additional Note: Helps slow the progression of the disease.

Prostacyclin Mimetics:

• Medication Name: Tyvaso DPI (Inhaled)
• Function: Works to widen constricted blood vessels in the lungs, promoting better circulation.
• Typical Side Effects: Cough, nausea, headaches, throat irritation, flushing, and dizziness.
• Administration: Delivered through inhalation.
• Additional Note: Enhances the ability to perform physical activities and delays symptom progression.

Biologics: biologics helps keep the walls of the blood vessels from thickening
Sotatercept-(csrk) (Winrevair):

• Medication Names: Sotatercept-csrk (Winrevair)
• What It Does: This medicinal product works to correct imbalances that impact the structure of your blood vessels
  Common Side Effects: Headache, rash, nosebleed, tiny blood vessels that look pink or red on the skin, dizziness, diarrhea, redness
• Delivery Method: Subcutaneous (SC)
• Additional Information: It improves the capability to do physical activity, and reduces the risk of physical condition and symptoms worsening. Those who are looking to buy Sotatercept-csrk (Winrevair) in India can Call/WhatsApp: +91 9310090915.

Combination Medications: Combination therapies support blood vessels in remaining open.
Macitentan and Tadalafil:

• Medication Name: Opsynvi
• How It Works: These drugs prevent arterial wall thickening and organ damage, encouraging muscle relaxation and dilation of blood vessels.
• Potential Side Effects: Fluid retention, headaches or migraines, and anemia.
• Administration: Oral
• Additional Benefits: Slows disease progression, lowers hospitalization risk, and enhances physical activity.

Supportive Treatments: A healthcare provider (HCP) may suggest supportive treatments to manage PAH, which can include:

• Medications: Several types of medicines might be prescribed:
• Blood thinners to reduce the risk of blood clots.
• Digoxin to regulate the heartbeat.
• Diuretics (water pills) to remove excess fluid from the body.
• Oxygen therapy to ensure adequate oxygen levels.

Surgical Options: In some cases, surgical procedures might be necessary:

• Atrial septostomy creates an opening between the heart’s upper chambers to reduce pressure on the right side.
• Lung or heart-lung transplants may be an option for advanced cases.

Lifestyle Adjustments: PAH can impact daily living, but lifestyle changes can significantly improve your health and quality of life (QoL):

• Stay physically active within your limits.
• Stop smoking completely.
• Focus on a nutritious diet.
• Discuss pregnancy risks with your doctor.
• Prioritize mental health and emotional well-being.
• Avoid activities that strain your lungs or heart.