Inhaled Pulmonary Vasodilators: An Overview (2025)

Inhaled pulmonary vasodilators are a vital class of medications used to treat various pulmonary conditions, including pulmonary hypertension and acute respiratory distress syndrome (ARDS).

By targeting the pulmonary vasculature directly, these medications help reduce pulmonary artery pressure and improve oxygenation without causing systemic side effects.

This article explores how inhaled pulmonary vasodilators work, their common uses, and the key medications in this category, shedding light on their critical role in managing severe respiratory conditions.

What are Inhaled Pulmonary Vasodilators?

Inhaled pulmonary vasodilators are medications that relax and widen the blood vessels (pulmonary arteries) in the lungs, helping to reduce pulmonary vascular resistance. They are primarily used to treat conditions like pulmonary hypertension, acute respiratory distress syndrome (ARDS), and right-sided heart failure, where elevated pulmonary artery pressure impairs oxygen exchange.

These medications work by targeting the smooth muscle cells lining the pulmonary arteries, prompting them to relax and expand. Nitric oxide (NO) is the most commonly used inhaled pulmonary vasodilator, directly inducing vasodilation and lowering pulmonary arterial pressure. Prostacyclins like epoprostenol and iloprost can also be inhaled to achieve similar effects.

One of the significant benefits of inhaled administration is its targeted action. Unlike systemic vasodilators, which can cause widespread drops in blood pressure, inhaled pulmonary vasodilators primarily affect the lungs, reducing the risk of systemic hypotension.

These medications are frequently administered in critical care settings, often using devices like nebulizers or gas delivery systems. Their selective action makes them essential for managing severe respiratory and cardiac conditions in both pediatric and adult patients.

Types of Inhaled Pulmonary Vasodilators

Inhaled pulmonary vasodilators are generally categorized based on their chemical structure and mechanism of action. Some of the most commonly used types include:

• Nitric oxide
• Iloprost
• Treprostinil

Nitric Oxide (NO)

Nitric oxide (NO) is a widely used inhaled pulmonary vasodilator, particularly effective in treating conditions like persistent pulmonary hypertension of the newborn (PPHN), acute respiratory distress syndrome (ARDS), and severe hypoxemic respiratory failure. It works by relaxing the smooth muscle cells lining the pulmonary arteries, leading to vessel dilation, reduced pulmonary artery pressure, and improved oxygenation.

A key advantage of nitric oxide is its rapid onset of action, providing immediate therapeutic effects when administered. Its inhaled delivery targets the lungs directly, minimizing systemic side effects like hypotension.

However, careful monitoring is essential due to potential complications, including methemoglobinemia (a condition where hemoglobin’s oxygen-carrying capacity is impaired) and rebound pulmonary hypertension if the medication is discontinued too quickly. This makes precise dosing and gradual weaning critical in its clinical use.

Iloprost

Iloprost is a synthetic prostacyclin analogue commonly used as an inhaled pulmonary vasodilator, particularly for managing pulmonary arterial hypertension (PAH). It plays a crucial role in improving exercise capacity, delaying disease progression, and enhancing overall quality of life in affected patients. Iloprost is often used as part of long-term therapy in PAH management.

Iloprost works by activating prostacyclin receptors on the smooth muscle cells of the pulmonary arteries. This activation triggers vasodilation, reducing pulmonary artery pressure and inhibiting platelet aggregation, which helps prevent blood clots in the lungs.

One of iloprost’s advantages is its relatively longer half-life compared to other prostacyclins, allowing for fewer inhalation sessions throughout the day. However, patients should be monitored for potential side effects such as cough, throat irritation, headache, flushing, and bronchospasm. Careful dose adjustment and administration technique can help minimize these adverse effects, making iloprost a valuable option for long-term pulmonary vasodilation therapy.

Treprostinil

Treprostinil is a synthetic prostacyclin analogue used to manage pulmonary arterial hypertension (PAH). It can be administered through various routes, including oral, subcutaneous, intravenous, and inhalation. The inhaled form provides targeted pulmonary vasodilation with fewer systemic side effects, making it an essential option for patients with advanced PAH.

Treprostinil works by relaxing vascular smooth muscle cells through prostacyclin receptor activation, leading to reduced pulmonary artery pressure. It also inhibits platelet aggregation, helping to prevent blood clots that can worsen PAH.

Compared to other prostacyclins like iloprost, treprostinil has a longer half-life, enabling sustained therapeutic effects with less frequent dosing. This extended duration makes it suitable for long-term management and as a step-up therapy when first-line treatments prove insufficient.

Common side effects of inhaled treprostinil include cough, headache, throat irritation, and gastrointestinal discomfort. Close monitoring and individualized dosing are essential to ensure optimal therapeutic outcomes while minimizing adverse effects.

Inhaled Pulmonary Vasodilators Practice Questions

1. Why are inhaled pulmonary vasodilators administered?
They are administered to treat pulmonary hypertension.

2. Has the use of inhaled nitric oxide gas to treat neonates with persistent pulmonary hypertension been approved by the FDA?
Yes, it has been approved.

3. Which two inhaled pulmonary vasodilators have been FDA-approved for the treatment of pulmonary hypertension?
Iloprost and treprostinil

4. When is nitric oxide indicated?
It’s indicated for the treatment of neonates greater than 34 weeks of gestational age with hypoxic respiratory failure.

5. What is a brand of nitric oxide?
INOmax

6. When is iloprost indicated?
It is indicated for the treatment of pulmonary hypertension.

7. How can iloprost be administered?
It can be administered with an I-neb nebulizer.

8. How does iloprost work?
It dilates the pulmonary arterial vascular beds and affects platelet aggregation.

9. What are some adverse effects of iloprost?
Pulmonary edema, syncope, headache, and increased cough

10. When is treprostinil indicated?
It is indicated for the treatment of pulmonary arterial hypertension.

11. What is a brand of treprostinil?
Tyvaso

12. How is treprostinil administered?
It can be administered using an ultrasonic pulsed-delivery device known as a Tyvaso Inhalation System.

13. How does treprostinil work?
It dilates the pulmonary and systemic arterial vascular beds and inhibits platelet aggregation.

14. What is a potential negative side effect of treprostinil?
It may cause bronchospasm.

15. Can you mix treprostinil with other agents?
No, this drug should not be mixed.

16. Which drug is used to treat persistent pulmonary hypertension in neonates?
Nitric oxide

17. How does a nitric oxide treatment work?
It relaxes the vascular smooth muscle tissue by binding to the heme group of cytosolic guanylate cyclase, which activates guanylate cyclase and increases cyclic guanosine monophosphate.

18. What happens when nitric oxide is inhaled?
It produces pulmonary vasodilation, reduces pulmonary artery pressure, and improves V/Q mismatching.

19. What is a contraindication of nitric oxide?
It is contraindicated in neonates with dependent right-to-left shunts.

20. What is a common adverse effect that occurs when nitric oxide is given?
Hypotension

21. What drug is indicated to increase walking distance in patients?
Treprostinil (Tyvaso)

22. What is the dose availability of treprostinil?
It comes in a 2.9 mL ampule which contains 1.74 mg of treprostinil (0.6 mg/mL).

23. What should you do if treprostinil is not tolerated well by the patient?
The dose should be reduced to 1-2 breaths per session.

24. When is it indicated to increase the dose of treprostinil to three breaths?
You can increase the dose every 1-2 weeks until a dose of nine breaths per session has been reached.

25. Does nitric oxide act as a pulmonary vasodilator, improve pulmonary blood flow, and improve the PaO2 level?
Yes, yes it does.

26. How does nitric oxide affect systemic blood pressure?
It does not have an effect on systemic blood pressure.

27. Is nitric oxide a selective pulmonary vasodilator?
Yes, because it’s inhaled and only goes to the ventilated lung areas.

28. What is an indication of iNO?
Refractory hypoxemia related to an increased pulmonary artery pressure

29. What are two more indications of iNO?
Right heart failure and an increased PVR

30. What are the contraindications of iNO?
CHF, left heart failure, and methemoglobin reductase deficiency

31. What is the standard initial dose for iNO?
20-40 ppm

32. What level should an iNO dose not exceed?
80 ppm

33. What dose is used for weaning and discontinuing iNO?
Less than 20 ppm

34. What is the half life of iNO?
Less than 5 seconds

35. Will the methemoglobin level increase or decrease with iNO?
It may increase as a side effect.

36. Will nitrogen dioxide levels increase or decrease with iNO?
They may increase as a side effect.

37. What happens if a patient is weaned too quickly from iNO?
Rebound pulmonary hypertension can occur

38. Why does inhaled nitric oxide work so well?
It dilates blood vessels around the alveoli, which helps to open them up.

39. Does inhaled nitric oxide improve V/Q mismatch and oxygenation?
Yes, yes it does.

40. What should you do before removing a patient from nitric oxide?
Before removing the patient, you should make sure that the cylinder is turned off.

41. What are some examples of inhaled pulmonary vasodilators?
Nitric oxide, iloprost (Ventavis), and treprostinil (Tyvaso).

42. How do inhaled pulmonary vasodilators work?
They relax the pulmonary arteries, reduce pulmonary artery pressure, and improve oxygenation by dilating blood vessels in ventilated lung areas.

43. Are there any risks associated with inhaled pulmonary vasodilators?
Yes, potential risks include hypotension, rebound pulmonary hypertension, methemoglobinemia, and bronchospasm.

44. How are inhaled pulmonary vasodilators administered?
They are administered via inhalation devices such as nebulizers, specialized inhalation systems, or ventilator circuits.

45. Can inhaled pulmonary vasodilators be used long-term?
Yes, drugs like iloprost and treprostinil are often used long-term in managing chronic pulmonary arterial hypertension.

46. Why are inhaled pulmonary vasodilators preferred over systemic vasodilators?
They selectively target the lungs, reducing pulmonary artery pressure without causing systemic hypotension.

47. What monitoring is required during inhaled nitric oxide therapy?
Continuous monitoring of oxygenation, methemoglobin levels, and nitrogen dioxide levels is required to detect potential side effects.

48. What is the primary goal of inhaled pulmonary vasodilator therapy?
To reduce pulmonary artery pressure and improve gas exchange in patients with pulmonary hypertension or other related conditions.

49. What are the storage requirements for nitric oxide?
It should be stored in high-pressure gas cylinders at room temperature in a well-ventilated area.

50. Can inhaled pulmonary vasodilators be used during mechanical ventilation?
Yes, they can be administered through the ventilator’s inspiratory circuit.

51. How is methemoglobin managed in patients receiving inhaled nitric oxide?
Methemoglobin levels are monitored regularly, and treatment with methylene blue is considered if levels become dangerously high.

52. Can inhaled pulmonary vasodilators be used in emergency settings?
Yes, they are often used in critical care settings to manage severe hypoxemia and pulmonary hypertension.

53. How does nitric oxide affect oxygenation?
It improves oxygenation by dilating pulmonary vessels in well-ventilated alveoli, reducing V/Q mismatch.

54. Why is treprostinil contraindicated in patients with severe asthma?
It can cause bronchospasm, worsening respiratory status in asthmatic patients.

55. What is the difference between nitric oxide and iloprost?
Nitric oxide is a gas used primarily in acute care, while iloprost is a liquid medication administered through a nebulizer for chronic management.

56. What is rebound pulmonary hypertension?
A dangerous increase in pulmonary artery pressure that can occur if inhaled pulmonary vasodilators are withdrawn too quickly.

57. Why is nitric oxide considered a selective pulmonary vasodilator?
It targets only the lungs because it is inhaled and rapidly inactivated when it enters the bloodstream.

58. How is treprostinil dosed for inhalation therapy?
It typically starts with 3 breaths per session, up to 9 breaths per session, four times daily.

59. What are potential complications of prolonged nitric oxide use?
Methemoglobinemia, nitrogen dioxide buildup, and rebound pulmonary hypertension.

60. Can inhaled pulmonary vasodilators be used during pregnancy?
Their use is generally avoided unless the benefits outweigh the risks, as data on safety during pregnancy are limited.

61. What conditions other than pulmonary hypertension can benefit from inhaled nitric oxide?
Conditions such as acute respiratory distress syndrome (ARDS) and persistent pulmonary hypertension of the newborn (PPHN).

62. What is the initial dose of treprostinil for pulmonary hypertension?
Usually, it starts at 18 mcg (3 breaths) per session, up to 54 mcg (9 breaths) per session.

63. How do you manage a nitric oxide overdose?
Discontinue nitric oxide, administer oxygen, and treat methemoglobinemia if present.

64. What is a contraindication for using inhaled nitric oxide in newborns?
Neonates with congenital heart defects dependent on right-to-left shunting should not receive nitric oxide.

65. How is the effectiveness of inhaled pulmonary vasodilators evaluated?
By monitoring improvements in oxygenation, reduced pulmonary artery pressures, and increased exercise tolerance in chronic cases.

66. What delivery system is commonly used for iloprost administration?
The I-neb Adaptive Aerosol Delivery (AAD) system is typically used.

67. How often should iloprost be inhaled?
It is usually administered 6-9 times per day at 2-3 hour intervals.

68. Why should iloprost doses be spaced throughout the day?
To maintain stable pulmonary vasodilation and reduce symptom recurrence.

69. Why must inhaled vasodilators be administered under medical supervision?
Due to risks such as hypotension, rebound pulmonary hypertension, and airway irritation.

70. What should be done if a patient experiences severe side effects from inhaled vasodilators?
Stop the treatment immediately and provide supportive care, including oxygen therapy and medication adjustment.

71. What is the primary use of inhaled pulmonary vasodilators?
To treat pulmonary arterial hypertension and improve oxygenation by reducing pulmonary artery pressure.

72. Why are inhaled pulmonary vasodilators less likely to cause systemic hypotension?
They work directly in the lungs and have minimal systemic absorption.

73. How does inhaled nitric oxide improve ventilation-perfusion (V/Q) matching?
By dilating pulmonary vessels in well-ventilated lung areas, enhancing oxygen exchange.

74. What happens if inhaled pulmonary vasodilators are suddenly discontinued?
Rebound pulmonary hypertension may occur, leading to a potential respiratory crisis.

75. Why should inhaled pulmonary vasodilators be administered using a precise delivery system?
Accurate dosing is essential to ensure effectiveness and prevent adverse effects.

76. What conditions can lead to the prescription of inhaled pulmonary vasodilators?
Pulmonary hypertension, acute respiratory distress syndrome (ARDS), and persistent pulmonary hypertension of the newborn (PPHN).

77. Can inhaled pulmonary vasodilators be used in neonates?
Yes, they are often used in neonates with persistent pulmonary hypertension of the newborn.

78. What safety precautions should be taken when using nitric oxide therapy?
Monitoring methemoglobin and nitrogen dioxide levels regularly to avoid toxicity.

79. How do inhaled vasodilators improve exercise capacity in pulmonary hypertension patients?
By reducing pulmonary vascular resistance, improving cardiac output during physical activity.

80. Why is treprostinil often preferred for long-term pulmonary hypertension management?
Its inhaled form allows direct pulmonary artery targeting, minimizing systemic side effects.

81. Why is rebound pulmonary hypertension dangerous?
It can cause severe respiratory distress and decreased oxygenation, requiring emergency intervention.

82. Why is precise dose titration important in nitric oxide therapy?
To prevent side effects like hypotension and ensure optimal therapeutic effect.

83. What is the role of methemoglobin in nitric oxide therapy monitoring?
Methemoglobin levels indicate the degree of nitric oxide’s oxidative effects on red blood cells.

84. Why are iloprost inhalation sessions frequent throughout the day?
To maintain consistent pulmonary artery relaxation and symptom control.

85. What factors determine the choice of inhaled pulmonary vasodilator?
The patient’s diagnosis, severity of the condition, and response to previous treatments.

86. What are common side effects of inhaled nitric oxide therapy?
Hypotension, methemoglobinemia, and increased nitrogen dioxide levels.

87. Can inhaled pulmonary vasodilators be used with other pulmonary medications?
Yes, but only under close medical supervision to avoid drug interactions.

88. Why must patients avoid missing doses of inhaled pulmonary vasodilators?
Missed doses can result in worsened symptoms and increased pulmonary artery pressure.

89. Why is methemoglobin monitoring critical during nitric oxide therapy?
Elevated levels can impair oxygen delivery, causing cyanosis and respiratory distress.

90. What delivery device is used for treprostinil inhalation?
The Tyvaso Inhalation System, designed for accurate and controlled drug delivery.

91. What role do pulmonary vasodilators play in treating ARDS?
They improve oxygenation by reducing pulmonary artery pressure and improving V/Q matching.

92. What is a serious complication of prolonged nitric oxide therapy?
Rebound pulmonary hypertension due to abrupt discontinuation.

93. How is rebound pulmonary hypertension managed?
By slowly tapering the nitric oxide dose and providing oxygen and supportive therapy.

94. Why must nitric oxide cylinders be handled with care?
They are high-pressure gas containers requiring safe storage and controlled use.

95. What is the mechanism of action of treprostinil?
It dilates pulmonary arteries and inhibits platelet aggregation, reducing pulmonary vascular resistance.

96. Why is continuous monitoring essential during nitric oxide therapy?
To detect adverse effects such as hypotension and methemoglobinemia early.

97. What are two contraindications for nitric oxide therapy?
Congenital heart defects with right-to-left shunting and methemoglobin reductase deficiency.

98. How does nitric oxide affect pulmonary vascular resistance?
It lowers pulmonary vascular resistance, easing the heart’s workload and improving oxygenation.

99. Why should inhaled pulmonary vasodilators not be used without prescription?
Improper use can cause severe side effects such as hypotension and respiratory failure.

100. Why is inhaled nitric oxide therapy used selectively?
Its effects are limited to the lungs, making it highly effective for targeted pulmonary treatment.

Final Thoughts

Inhaled pulmonary vasodilators offer a targeted approach to managing pulmonary hypertension and impaired oxygenation in a variety of clinical settings.

Their selective vasodilatory effects on the pulmonary vasculature can dramatically improve patient outcomes by enhancing gas exchange and reducing the workload on the right heart.

However, clinicians must be aware of the potential risks, such as rebound pulmonary hypertension and systemic hypotension, and need to adhere to best practice guidelines for their application.