Inhaled pulmonary vasodilators are essential in the management of acute and chronic respiratory disorders characterized by pulmonary hypertension and compromised gas exchange.
These pharmacological agents, such as nitric oxide and prostacyclins, work by dilating the pulmonary arteries, thereby reducing pulmonary vascular resistance and improving oxygenation.
The advantage of inhaled administration lies in its ability to selectively target the pulmonary vasculature, minimizing systemic side effects.
Despite their therapeutic potential, a comprehensive understanding of the clinical applications, mechanisms of action, and associated risks is essential for optimizing patient outcomes.
What are Inhaled Pulmonary Vasodilators?
Inhaled pulmonary vasodilators are medications designed to dilate, or widen, the blood vessels in the lungs (pulmonary arteries). These agents are typically used in the management of conditions characterized by increased pulmonary vascular resistance, such as pulmonary hypertension or acute respiratory distress syndrome (ARDS).
By dilating the blood vessels in the lungs, these medications improve blood flow and enhance the exchange of oxygen and carbon dioxide between the lungs and the bloodstream.
The most commonly used inhaled pulmonary vasodilator is nitric oxide (NO). Inhaled nitric oxide acts directly on the smooth muscle cells that line the pulmonary arteries, causing them to relax.
This leads to the widening of these vessels and a subsequent decrease in pulmonary arterial pressure. Prostacyclins like epoprostenol can also be administered through inhalation to achieve a similar effect.
One of the primary advantages of inhaled administration is that it allows the medication to act directly on the pulmonary vessels, reducing the risk of systemic side effects.
For instance, systemic vasodilators could potentially lower blood pressure throughout the entire circulatory system, leading to problems like systemic hypotension. In contrast, inhaled pulmonary vasodilators are more selective, predominantly affecting only the lung vasculature.
These medications are often used in critical care settings, such as intensive care units, and may be administered via a variety of devices, including nebulizers or gas cylinders.
They are generally considered a key therapeutic option for managing severe respiratory failure in both pediatric and adult populations.
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 is one of the most commonly used inhaled pulmonary vasodilators and is particularly effective for conditions like persistent pulmonary hypertension of the newborn (PPHN), acute respiratory distress syndrome (ARDS), and other forms of hypoxemic respiratory failure.
It works by directly relaxing the smooth muscle cells lining the pulmonary arteries.
One of its main advantages is the rapid onset of action, allowing for immediate therapeutic effects. Its inhaled administration allows it to act selectively on the pulmonary vasculature, reducing systemic side effects.
However, it is essential to monitor for potential complications such as methemoglobinemia and rebound pulmonary hypertension upon discontinuation.
Iloprost
Iloprost is a synthetic prostacyclin analogue often used as an inhaled pulmonary vasodilator. It is particularly beneficial for patients with pulmonary arterial hypertension (PAH) and can be used as part of long-term therapy.
Iloprost works by binding to the prostacyclin receptor, leading to vasodilation of the pulmonary arteries and reduced platelet aggregation.
It has a longer half-life compared to other prostacyclins, making it suitable for less frequent dosing. Iloprost is generally well-tolerated but may cause side effects like cough or bronchospasm, which mandates careful monitoring.
Treprostinil
Treprostinil is another synthetic prostacyclin analogue used for the treatment of pulmonary arterial hypertension. While it can be administered through various routes such as oral, subcutaneous, and intravenous, the inhaled form allows for targeted action on the pulmonary vasculature.
Treprostinil leads to relaxation of vascular smooth muscle cells and has anti-platelet properties.
Unlike iloprost, treprostinil has an even longer half-life, allowing for extended therapeutic coverage.
The inhaled form is commonly used as a step-up therapy for patients who have not responded adequately to other treatment modalities. Common side effects include cough, headache, and gastrointestinal issues.
Note: Each of these inhaled pulmonary vasodilators has unique pharmacological properties and associated risks, making it essential for clinicians to tailor the choice of medication to the specific clinical scenario.
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
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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.
FAQs About Inhaled Pulmonary Vasodilators
What are Inhaled Pulmonary Vasodilators?
Inhaled pulmonary vasodilators are a type of medication used to treat high blood pressure in the lungs. They work by opening up the pulmonary blood vessels, which allows more oxygen to be delivered throughout the body.
There are a number of different inhaled pulmonary vasodilators available, each with its own unique set of benefits and side effects.
What are Some Examples of Inhaled Pulmonary Vasodilators?
Some of the most common examples of inhaled pulmonary vasodilators include inhaled prostacyclin, nitric oxide, iloprost, and treprostinil.
How do Inhaled Pulmonary Vasodilators Work?
Inhaled pulmonary vasodilators work by opening up the pulmonary blood vessels, which allows more blood to flow through the lungs.
This allows more blood to reach the alveoli, where it can pick up oxygen molecules that can be transported throughout the body.
Are There Any Risks Associated With Inhaled Pulmonary Vasodilators?
Like all medications, inhaled pulmonary vasodilators come with a number of potential risks and side effects. Some of the most common risks include:
- Sudden drops in blood pressure
- An increase in heart rate
- Headache
- Nausea
- Dizziness
- Constipation
- Fluid retention
That is why this medication requires a direct order from a physician before administration for the treatment of pulmonary hypertension.
How are Inhaled Pulmonary Vasodilators Administered?
Inhaled pulmonary vasodilators are typically administered via inhaler or specialized aerosol delivery system.
The direct supervision of a physician or pulmonologist is often required during administration.
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.
Ongoing research into new agents and delivery mechanisms promises to further refine this essential tool in respiratory care.
Written by:
John Landry is a registered respiratory therapist from Memphis, TN, and has a bachelor's degree in kinesiology. He enjoys using evidence-based research to help others breathe easier and live a healthier life.
References
- Egan’s Fundamentals of Respiratory Care. 12th ed., Mosby, 2020.
- Rau’s Respiratory Care Pharmacology. 10th ed., Mosby, 2019.
- Wright BJ. Inhaled pulmonary vasodilators in refractory hypoxemia. Clin Exp Emerg Med. 2015.
- Kuch, B. A., Saville, A. L., Sanchez-De-Toledo, J., & Venkataraman, S. T. (2017, May 25). Inhaled Pulmonary Vasodilators: Are There Indications Within the Pediatric ICU? Respiratory Care.