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Nitric Oxide for Pulmonary Hypertension: Uses, Drug Interactions, and Blood Thinners

Medically reviewed by Vedran Radonić, M.D., Ph.D.
Written by Emily Wagner, M.S.
Updated on October 18, 2024

Pulmonary hypertension (PH) is a chronic condition affecting the lungs, leading to symptoms such as chest pain and shortness of breath. Fortunately, several medications can help manage PH, including a class called vasodilators. Vasodilators work by dilating (widening) blood vessels to help blood flow. One specific type of vasodilator, inhaled nitric oxide, is used for newborns, children, and adults with various types of PH to help reduce high blood pressure in the lungs.

In this article, we’ll discuss all things nitric oxide therapy, including what medications to avoid while you’re on it.

What Is Nitric Oxide?

Nitric oxide is a naturally occurring gas that relaxes and dilates blood vessels, playing an important role in maintaining normal blood pressure levels. When used as a therapy, inhaled nitric oxide acts as a selective pulmonary vasodilator, meaning it targets blood vessels in the lungs specifically without affecting the rest of the body. This localized effect sets it apart from many other PH treatments, which tend to be systemic (affect the whole body).

How does nitric oxide help the lungs? It enters the bloodstream and travels to the vascular smooth muscle (smooth muscle in blood vessel walls), where it relaxes and dilates the vessels, allowing more blood to flow through. This reduces the effort required by the heart to pump blood, leading to a decrease in blood pressure.

How Does Nitric Oxide Decrease Pulmonary Hypertension?

The U.S. Food and Drug Administration (FDA) first approved nitric oxide therapy in 1999. It’s a well-established treatment for conditions like persistent pulmonary hypertension of the newborn (PPHN). However, evidence for its benefits in treating other forms of pulmonary hypertension, especially in adults, is limited.

During nitric oxide therapy, a person inhales the gas through a mask or nasal cannula at an initial dose of 5 to 20 parts per million. The dose can be adjusted up to 80 parts per million if needed. Throughout treatment, health care providers monitor blood oxygen levels, pulmonary arterial pressure (the pressure in the lungs), and overall blood pressure.

Nitric Oxide for Persistent Pulmonary Hypertension of the Newborn

Persistent pulmonary hypertension of the newborn occurs when a newborn’s lung blood vessels do not open properly, leading to low oxygen levels that can affect the brain and other organs. Opening these blood vessels quickly is crucial to ensure the baby gets enough oxygen.

Inhaled nitric oxide is a key treatment for PPHN, helping to widen the lung blood vessels and improve blood flow. The baby inhales nitric oxide through their mouth or nasal cannula, often in combination with a ventilator — a machine that helps move air in and out of the lungs to assist with breathing.

Nitric Oxide for Pulmonary Arterial Hypertension

Pulmonary arterial hypertension (PAH) is a type of PH that affects both children and adults. It can be caused by various factors, including genetics, certain medications, and other conditions like sleep apnea (where breathing repeatedly stops and starts during sleep) or autoimmune diseases. PAH specifically involves the narrowing of arteries in the lungs, forcing the heart to work harder to push blood through them.

Inhaled nitric oxide gas is sometimes used to treat PAH, though it’s not specifically FDA approved for adults with the condition, and its effectiveness may vary. People are categorized as either “responders” or “nonresponders” depending on how well nitric oxide lowers their pulmonary vascular resistance (resistance of blood flow) and mean pulmonary artery pressure (blood pressure within the lungs’ arteries).

Other PAH medications work similarly to nitric oxide. For example, phosphodiesterase (PDE) inhibitors prevent the breakdown of a molecule called cyclic guanosine monophosphate (cGMP), which helps relax lung blood vessels, thereby lowering blood pressure. Sildenafil (Revatio, Viagra) is one such PDE inhibitor used for PAH.

Nitric Oxide for Postoperative Pulmonary Hypertension

PH can develop after surgeries for cardiovascular conditions, including:

  • Heart transplants
  • Congenital heart disease surgery
  • Placement of a left ventricular assist device (LVAD), a device that supports heart function in people with heart failure

Inhaled nitric oxide can help treat PH that arises after surgery and may reduce the need for more intensive treatments. It can also be administered before surgery to help prevent PH from occurring.

Advantages and Disadvantages of Nitric Oxide Therapy

Inhaled medication offers distinct advantages over systemic treatment. For example, nitric oxide affects only the lungs when inhaled, so it can be administered at high concentrations with fewer side effects compared to systemic vasodilators. The latter affects blood vessels throughout the entire body, which can cause low blood pressure or affect other organs.

Nitric oxide works by dilating blood vessels in the lungs, improving blood flow and oxygenation. It is quickly absorbed by hemoglobin in the blood, which inactivates the gas before it can affect other areas of the body.

However, there are drawbacks to inhaled therapies like nitric oxide. Individuals with sensitive airways may experience coughing or other breathing issues when inhaling the gas. Additionally, controlling the exact dose can be challenging, as each person’s breathing rate varies.

Medications To Avoid on Nitric Oxide Therapy

Many medications can interact with each other, posing risks when taken together. Nitric oxide therapy for pulmonary hypertension shouldn’t be combined with certain drugs, as the combination can cause a dangerous drop in blood pressure.

Major drugs to avoid while on nitric oxide include:

  • Nitrates, used to relieve angina (chest pain)
  • PDE5 inhibitors, such as sildenafil, tadalafil (Cialis), and vardenafil (Levitra)

Your doctor and pharmacist will take care to avoid prescribing these medications together because of the serious risks involved.

In rare and carefully monitored cases of severe pulmonary hypertension, a pulmonologist may prescribe both a PDE inhibitor and nitric oxide. Make sure to follow your doctor’s directions carefully and reach out if you have any questions or concerns.

Blood Thinners and Nitric Oxide Therapy

Many people with PAH wonder: Can you take nitric oxide with a blood thinner? The short answer is yes. Blood thinners play a crucial role in certain conditions and can be lifesaving.

Nitric oxide therapy should be managed by a specialist. Be sure to provide a complete list of all your medications at every doctor’s appointment to help ensure that all your treatments work safely together. Bring a complete list of all of your medications to each appointment to help ensure that all your treatments work safely together.

Talk With Others Who Understand

On myPHteam — the social network for people with pulmonary hypertension and their loved ones — more than 55,000 members come together to ask questions, give advice, and share their stories with others who understand life with pulmonary hypertension.

Have you tried nitric oxide to treat your pulmonary hypertension? Share your experience in the comments below, or start a conversation by posting on your Activities page.

References
  1. Inhaled Nitric Oxide in Adults: Biology and Indications for Use — Wolters Kluwer UpToDate
  2. Vasodilators — Mayo Clinic
  3. Vascular Endothelial Cell Biology: An Update — International Journal of Molecular Sciences
  4. Vascular Smooth Muscle Contraction in Hypertension — Cardiovascular Research
  5. Nitric Oxide — StatPearls
  6. Inhaled Nitric Oxide for Neonates With Persistent Pulmonary Hypertension of the Newborn in the Cinrgi Study: Time to Treatment Response — BMC Pediatrics
  7. Long-Term Inhalation of Nitric Oxide for a Patient With Primary Pulmonary Hypertension — Japanese Circulation Journal
  8. Nitric Oxide (Inhalation Gas) — University of Michigan Health
  9. Nitric Oxide and Pulmonary Arterial Hypertension — Global Cardiology Science & Practice
  10. Center for Drug Evaluation and Research — Approval Package for: Application Number: NDA 20845/ S17 — U.S. Food and Drug Administration
  11. Nitric Oxide (Inhalation Route) — Mayo Clinic
  12. Inhaled Nitric Oxide: A Selective Pulmonary Vasodilator: Current Uses and Therapeutic Potential — Circulation
  13. Left Ventricular Assist Devices (LVADs) — Cleveland Clinic
  14. Nitric Oxide and Pulmonary Hypertension — Korean Journal of Anesthesiology
  15. Persistent Pulmonary Hypertension of the Newborn (PPHN) — UCSF Benioff Children’s Hospitals
  16. Drug-Drug Interactions in the Management of Patients With Pulmonary Arterial Hypertension — Chest
  17. Inhaled NO and Sildenafil Combination in Cardiac Surgery Patients With Out-of-Proportion Pulmonary Hypertension: Acute Effects on Postoperative Gas Exchange and Hemodynamics — Circulation: Heart Failure
  18. Heparin Reacts With and Inactivates Nitric Oxide — Journal of Cardiovascular Pharmacology and Therapy

Updated on October 18, 2024

A myPHteam Member

Paul I have heard that there is nothing that can help group 3 with possible exception of Slidenifil. If you hear of anything different, please let me know as well and I shall to the same in return… read more

May 16
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How Is The NO Treatment Given In Clinic Or At Home And For What Duration?

May 16, 2024 by A myPHteam Member 1 answer
Vedran Radonić, M.D., Ph.D. completed medical school and his Ph.D. at the University of Zagreb, Croatia. Learn more about him here.
Emily Wagner, M.S. holds a Master of Science in biomedical sciences with a focus in pharmacology. She is passionate about immunology, cancer biology, and molecular biology. Learn more about her here.

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