Pulmonary Hypertension Agents

Verified · Oct 2026

Prototype: bosentan

Pulmonary Hypertension Agents are a class of medications used for pulmonary arterial hypertension.

Medical view → mechanisms, drug comparisons and Step 1 pharmacology

In pulmonary arterial hypertension the lung arteries make too little nitric oxide and prostacyclin and too much endothelin-1. Each drug family here corrects one of those signals — and each brings its own non-negotiable safety rule.

How it works in the body

The system involved, what goes wrong, and how the drug and body interact.

01 Why the pulmonary arteries narrow

Pulmonary hypertension is grouped by cause into five WHO groups. Group 1 is pulmonary arterial hypertension (PAH) — idiopathic, heritable, or linked to connective tissue disease, HIV, portal hypertension, drugs and toxins. Group 3 is pulmonary hypertension from lung disease or hypoxemia, and Group 4 from obstruction of the pulmonary arteries, most often from venous thromboembolism.

In PAH, endothelial and smooth muscle cells proliferate and thicken the walls of the small pulmonary arteries. The endothelium makes less nitric oxide and prostacyclin (vasodilators) and more endothelin-1 (a vasoconstrictor). The narrowed vessels raise the afterload on the right ventricle, which hypertrophies, then dilates — untreated, the disease carries very high mortality from right-sided heart failure. The drugs improve symptoms and slow progression, but none is a cure.

02 Three pathways, three drug families

Endothelin pathway. Endothelin-1 acts on two receptors: ETA (vasoconstriction and cell proliferation) and ETB (vasodilation, antiproliferation and clearance of endothelin-1). Endothelin receptor antagonists (ERAs) block them — bosentan and macitentan block both receptors, while ambrisentan is highly selective for ETA.

Nitric oxide–cGMP pathway. Nitric oxide binds soluble guanylate cyclase (sGC), which makes cGMP; cGMP relaxes vascular smooth muscle, and the enzyme PDE-5 — the predominant phosphodiesterase in the pulmonary vessels — breaks it down. Sildenafil and tadalafil inhibit PDE-5 so cGMP builds up. Riociguat works one step earlier: it sensitizes sGC to the body’s own nitric oxide and also stimulates sGC directly, even without nitric oxide.

Prostacyclin pathway. Prostacyclin (PGI2) binds the IP receptor, which raises cAMP, relaxing smooth muscle and inhibiting platelet aggregation. Epoprostenol (synthetic prostacyclin) and treprostinil (a stable prostacyclin analog) replace the missing signal: they dilate the pulmonary and systemic arteries and inhibit platelet aggregation.

The generic names carry WHO stems: -entan (endothelin receptor antagonists), -afil (PDE-5 inhibitors with vasodilator action), -ciguat (guanylate cyclase activators and stimulators) and prost (prostaglandins).

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Each family corrects one of the three abnormal signals in PAH.

03 Why the same safety rules keep coming back

Pregnancy. The three ERAs and riociguat share a boxed warning for embryo-fetal toxicity: pregnancy is excluded before starting, effective contraception is used before, during and for one month after treatment, and the drug is stopped as soon as pregnancy is detected. Bosentan adds a boxed warning for hepatotoxicity and is available only through a REMS program.

Two ways to raise cGMP is one too many. Nitrates and nitric oxide donors increase cGMP formation; PDE-5 inhibitors block its breakdown; riociguat drives sGC directly. Any two together can cause severe hypotension, so nitrates, PDE-5 inhibitors and riociguat are contraindicated in combination.

Never interrupt a prostacyclin. Epoprostenol’s half-life in the body is expected to be no more than about 6 minutes, and treprostinil’s is about 4 hours. Interrupting the infusion or a sudden large dose reduction can cause rebound pulmonary hypertension — a death was attributed to an interruption of epoprostenol.

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Nitrates, PDE-5 inhibitors and riociguat each push cGMP up — together they cause severe hypotension.

Drug names

Generic Brand

bosentan Tracleer

ambrisentan Letairis

macitentan Opsumit

sildenafil Revatio

tadalafil Adcirca, Alyq, Tadliq

riociguat Adempas

epoprostenol Veletri

treprostinil Remodulin, Tyvaso, Tyvaso DPI, Orenitram

Indications

Pulmonary arterial hypertension (PAH, WHO Group 1) — every drug on this page
Bosentan (idiopathic or congenital PAH, age 3 and older) and sildenafil (ages 1 to 17) for PAH in children
Riociguat for chronic thromboembolic pulmonary hypertension (CTEPH, WHO Group 4) that persists or recurs after surgery or is inoperable
Inhaled treprostinil (Tyvaso, Tyvaso DPI) for pulmonary hypertension associated with interstitial lung disease (PH-ILD, WHO Group 3)
Treprostinil infusion (Remodulin) for patients with PAH who need to transition from epoprostenol

Mechanism of action

Three mechanisms. Endothelin receptor antagonists block endothelin-1 at ETA receptors (vasoconstriction, proliferation) — bosentan and macitentan at both ETA and ETB, ambrisentan selectively at ETA. PDE-5 inhibitors (sildenafil, tadalafil) block the breakdown of cGMP in pulmonary vascular smooth muscle, relaxing it and dilating the pulmonary vascular bed. Riociguat stimulates soluble guanylate cyclase, both sensitizing it to endogenous nitric oxide and stimulating it independently of nitric oxide, increasing cGMP. Epoprostenol and treprostinil are prostacyclin and a prostacyclin analog that directly dilate the pulmonary and systemic arterial beds and inhibit platelet aggregation.

In plain terms

They either block the vessel-tightening signal (endothelin) or boost the vessel-relaxing signals (nitric oxide–cGMP and prostacyclin) in the lung arteries.

Therapeutic effects — what you'll see working

Success is measured as better exercise capacity (often a 6-minute walk test), a better functional class, and fewer episodes of clinical worsening — the drugs improve quality of life but do not cure PAH.

Better exercise capacity Delayed clinical worsening Lower pulmonary pressure and resistance

Better exercise capacity: Most labels name better exercise ability or capacity as a goal (Remodulin: fewer symptoms with exercise); the 6-minute walk test is commonly used to assess it.
Delayed clinical worsening: Macitentan, and ambrisentan with tadalafil, reduce the risk of disease progression and hospitalization; oral treprostinil delays disease progression; ambrisentan, sildenafil and riociguat delay clinical worsening, and bosentan decreases it.
Lower pulmonary pressure and resistance: Vasodilation lowers pulmonary arterial pressure and vascular resistance and reduces right-ventricular afterload, improving cardiac output.

Adverse effects

Most effects come from vasodilation (headache, flushing, low blood pressure). The serious ones are drug-family specific: fetal harm and liver injury with the ERAs, cGMP-stacking hypotension, and the dangers of a prostacyclin line — interruption and infection.

■ Boxed warning — embryo-fetal toxicity (bosentan, ambrisentan, macitentan, riociguat) Hold & notify

Fetal harm with bosentan, ambrisentan, macitentan and riociguat — all are contraindicated in pregnancy.

Exclude pregnancy before starting in females of reproductive potential, use effective contraception before, during and for one month after treatment, and stop the drug as soon as pregnancy is detected. Bosentan lowers hormonal-contraceptive levels, so hormonal methods must not be the only contraception with bosentan.

■ Boxed warning — hepatotoxicity (bosentan) Hold & notify

Bosentan can raise liver aminotransferases and cause liver failure, so it is available only through the Bosentan REMS.

In trials, bosentan raised ALT/AST to at least 3× ULN in about 11% of patients. Aminotransferases are measured before starting and then monthly; bosentan is stopped if elevations come with symptoms of liver injury (nausea, vomiting, fever, abdominal pain, jaundice, unusual lethargy or fatigue) or bilirubin ≥ 2× ULN. Prescribers, patients and pharmacies must enroll in the REMS. Macitentan’s label also warns that ERAs cause hepatotoxicity and liver failure (baseline liver enzymes, then as clinically indicated), whereas aminotransferase elevations > 3× ULN occurred in 0% on ambrisentan versus 2.3% on placebo in 12-week trials.

Hypotension (PDE-5 inhibitors, riociguat, prostacyclins) Hold & notify

Sildenafil, tadalafil, riociguat, epoprostenol and treprostinil dilate systemic vessels and lower blood pressure — lightheadedness, dizziness, chest pain.

Patients with resting hypotension, fluid depletion, left-ventricular outflow obstruction or autonomic dysfunction, or those taking antihypertensives, are most at risk. The riociguat label advises considering a dose reduction if hypotension develops.

Prostacyclins · rebound pulmonary hypertension if interrupted Report immediately

Stopping suddenly, an infusion interruption, or a large dose cut can cause rebound PAH — potentially fatal.

Abrupt withdrawal of epoprostenol causes rebound symptoms such as dyspnea, dizziness and asthenia, and one death was attributed to an interruption. Treprostinil labels (infusion and oral) warn of worsening PAH with abrupt withdrawal or sudden large dose reductions. Any interruption in drug delivery — pump failure, a blocked or broken catheter, running out of drug — is an emergency.

Prostacyclin infusions · catheter-related bloodstream infection Report immediately

Chronic IV infusion through a central venous catheter carries a risk of bloodstream infection and sepsis, which may be fatal.

This risk is why subcutaneous treprostinil is preferred over IV. Strict aseptic technique is required when preparing and giving epoprostenol. Fever or signs of infection in a patient with a central line must be reported right away.

ERAs · fluid retention and falling hemoglobin Hold & notify

Peripheral edema and fluid retention; hemoglobin and hematocrit decrease early, then stabilize.

Fluid retention can develop within weeks of starting and may need diuretics or hospitalization for decompensated heart failure; patients with left-ventricular dysfunction are at particular risk. Hemoglobin falls within the first weeks — postmarketing anemia with bosentan has required transfusion. ERAs can also decrease sperm counts.

PDE-5 inhibitors · sudden vision or hearing loss, prolonged erection Report immediately

Non-arteritic anterior ischemic optic neuropathy (NAION), sudden hearing loss, and priapism.

Sudden loss of vision in one or both eyes can be NAION and may be permanent; sudden decrease or loss of hearing may come with tinnitus and dizziness. An erection lasting more than 4 hours needs emergency care. Sildenafil is about 10 times as potent for PDE-5 as for the retinal enzyme PDE-6, which is thought to explain the color-vision changes seen at higher doses.

Pulmonary edema — possible pulmonary veno-occlusive disease (PVOD) Report immediately

Pulmonary vasodilators can badly worsen PVOD; new pulmonary edema after starting suggests it.

The ERAs, PDE-5 inhibitors and riociguat all carry this warning. If pulmonary edema appears, PVOD should be considered — riociguat is stopped if PVOD is confirmed, and epoprostenol should not be used long-term in patients who develop pulmonary edema during dose initiation.

Bleeding (prostacyclins, riociguat) and nosebleeds (sildenafil) Hold & notify

Treprostinil and epoprostenol inhibit platelet aggregation; riociguat caused serious bleeding; sildenafil increases epistaxis.

Serious bleeding occurred in 2.4% of patients on riociguat versus 0% on placebo, including serious hemoptysis (one fatal). With sildenafil, epistaxis was 13% in PAH from connective tissue disease and was more frequent with a vitamin K antagonist. Epoprostenol may add to the bleeding risk of anticoagulants and antiplatelet drugs.

Inhaled treprostinil · bronchospasm Hold & notify

Like other inhaled prostaglandins, inhaled treprostinil can cause acute bronchospasm; cough and throat irritation are common.

Patients with asthma, COPD or other bronchial hyperreactivity are at increased risk; their airway disease should be treated optimally before and during treatment.

Common — vasodilator effects Expected

Headache, flushing, jaw pain, diarrhea and nausea (prostacyclins); headache, dyspepsia and flushing (PDE-5 inhibitors); peripheral edema and nasal congestion (ERAs); infusion-site pain (subcutaneous treprostinil).

These follow the main pharmacologic effect. Subcutaneous treprostinil infusion-site pain and reaction are its most common adverse reactions; the oral form mostly causes GI upset and the inhaled form cough and throat irritation.

Interactions

Nitrates (nitroglycerin, isosorbide) or nitric oxide donors (amyl nitrite) + sildenafil, tadalafil or riociguat drug

Both sides raise cGMP → severe hypotension. Contraindicated; nitrates are not given within 48 hours of the last tadalafil dose.

Riociguat + a PDE-5 inhibitor (sildenafil, tadalafil, vardenafil) or dipyridamole/theophylline drug

Contraindicated (hypotension). Stop sildenafil at least 24 hours and tadalafil at least 48 hours before riociguat; stop riociguat at least 24 hours before a PDE-5 inhibitor.

Other PDE-5 inhibitors (sildenafil as Viagra, tadalafil as Cialis) drug

The combination has not been studied — patients on Revatio or a tadalafil PAH product should not take another PDE-5 inhibitor.

Alpha-blockers, antihypertensives or substantial alcohol + PDE-5 inhibitors drug

Additive blood-pressure lowering; substantial alcohol (5 or more units) with tadalafil increases orthostatic signs and symptoms.

Strong CYP3A inhibitors (ketoconazole, itraconazole, ritonavir) drug

Raise levels of sildenafil (not recommended), tadalafil (avoid) and macitentan (avoid); strong CYP and P-gp/BCRP inhibitors raise riociguat exposure and may cause hypotension. With bosentan, a CYP2C9 inhibitor plus a strong or moderate CYP3A inhibitor is not recommended.

Strong CYP3A inducers (rifampin) and bosentan as an inducer drug

Lower levels of tadalafil and macitentan (avoid), riociguat and sildenafil. Bosentan induces CYP3A and CYP2C9 — it lowers sildenafil and hormonal contraceptive levels, so hormonal methods must not be the only contraception.

Cyclosporine drug

Contraindicated with bosentan (markedly higher bosentan levels); with ambrisentan, the ambrisentan dose is capped.

Gemfibrozil (CYP2C8 inhibitor) or rifampin (CYP2C8 inducer) + treprostinil drug

Gemfibrozil increases and rifampin decreases treprostinil exposure — dose adjustment may be needed when they are added or withdrawn.

Anticoagulants and antiplatelet drugs + prostacyclins; vitamin K antagonists + sildenafil drug

Prostacyclins inhibit platelet aggregation and may add to bleeding risk; epistaxis with sildenafil was more frequent with a vitamin K antagonist.

Antacids (aluminum/magnesium hydroxide) + riociguat drug

Reduce riociguat absorption — separate by at least 1 hour.

Contraindications

The absolute rows come from the labels’ contraindication sections. The most testable: pregnancy with an ERA or riociguat, and never combining a nitrate, a PDE-5 inhibitor and riociguat.

Pregnancy (bosentan, ambrisentan, macitentan, riociguat)

Boxed warning — these drugs may cause fetal harm based on animal data.

Sildenafil or tadalafil with organic nitrates in any form, regularly or intermittently — no nitrate within 48 hours of the last tadalafil dose

PDE-5 inhibitors potentiate the hypotensive effect of nitrates through the combined effect on the nitric oxide–cGMP pathway.

Riociguat with nitrates or nitric oxide donors (such as amyl nitrite) in any form

The combination causes hypotension.

Riociguat with a PDE-5 inhibitor (sildenafil, tadalafil, vardenafil) or a nonspecific PDE inhibitor (dipyridamole, theophylline)

Hypotension. Riociguat is not given within 24 hours of sildenafil, or 24 hours before or within 48 hours after tadalafil; riociguat is stopped at least 24 hours before a PDE-5 inhibitor is started.

Riociguat with another soluble guanylate cyclase stimulator

Labeled contraindication (pharmacodynamic interaction).

Bosentan with cyclosporine A or with glyburide

Cyclosporine markedly increases bosentan concentrations; glyburide with bosentan increased the risk of liver enzyme elevations.

Ambrisentan: idiopathic pulmonary fibrosis, including IPF with pulmonary hypertension (WHO Group 3)

In a trial in IPF, ambrisentan showed a greater risk of disease progression or death.

Riociguat: pulmonary hypertension associated with idiopathic interstitial pneumonias (PH-IIP)

Labeled contraindication.

Epoprostenol: chronic use in heart failure due to severe left-ventricular systolic dysfunction, or in patients who develop pulmonary edema during dose initiation

A heart-failure survival study was stopped for higher mortality with epoprostenol; pulmonary edema during initiation may signal PVOD.

Oral treprostinil (Orenitram): severe hepatic impairment (Child-Pugh C)

Systemic exposure increases.

Hypersensitivity to bosentan, macitentan, sildenafil, tadalafil or epoprostenol

Labeled contraindication — reported reactions include DRESS, anaphylaxis and angioedema (bosentan), anaphylaxis (sildenafil), and Stevens-Johnson syndrome and exfoliative dermatitis (tadalafil).

Resting hypotension, fluid depletion, left-ventricular outflow obstruction or autonomic dysfunction (PDE-5 inhibitors, riociguat) use caution

Vasodilation may cause symptomatic hypotension or ischemia.

Pulmonary veno-occlusive disease use caution

Pulmonary vasodilators may significantly worsen it; use is not recommended.

Bosentan: aminotransferases > 3× ULN before starting; ambrisentan: clinically significant anemia; macitentan: severe anemia use caution

Bosentan should generally be avoided (hepatotoxicity is harder to monitor); starting ambrisentan or macitentan is not recommended because they lower hemoglobin.

Retinitis pigmentosa or other hereditary degenerative retinal disorders (sildenafil, tadalafil) use caution

Use is not recommended — no safety data, and some patients have genetic disorders of retinal phosphodiesterases.

Pulmonary hypertension from sickle cell disease (sildenafil) use caution

Vaso-occlusive crises requiring hospitalization were more common with sildenafil.

Penile deformity or conditions predisposing to priapism — sickle cell anemia, multiple myeloma, leukemia (PDE-5 inhibitors) use caution

Use with caution — risk of priapism.

Asthma, COPD or other bronchial hyperreactivity (inhaled treprostinil) use caution

Increased risk of acute bronchospasm.

Oral treprostinil: diverticulosis, or moderate hepatic impairment use caution

The tablet shell does not dissolve and can lodge in a diverticulum; use is avoided in moderate hepatic impairment.

When to hold

Assess before giving — these findings mean hold the dose and act.

Bosentan — ALT/AST elevation with symptoms of liver injury (nausea, vomiting, fever, abdominal pain, jaundice, unusual lethargy or fatigue) or bilirubin ≥ 2× ULN

Hold and notify — the label says to discontinue bosentan.

Positive pregnancy test or suspected pregnancy on an ERA or riociguat

Hold and notify — the drug is discontinued as soon as possible when pregnancy is detected.

A prostacyclin infusion stops — pump alarm, occlusion, empty reservoir, broken or dislodged catheter

Restore delivery immediately (backup pump and supplies) and notify the prescriber — never leave it off. Epoprostenol rates are changed only on a prescriber’s direction except in a life-threatening situation (e.g., unconsciousness, collapse).

Fever, chills or signs of infection in a patient with a central line for a prostacyclin

Notify the prescriber immediately — possible catheter-related bloodstream infection or sepsis.

Sudden loss of vision or hearing, or an erection lasting more than 4 hours, on a PDE-5 inhibitor

Seek immediate medical attention (label instruction) and notify the prescriber.

New pulmonary edema (worsening dyspnea, crackles, hypoxemia) after starting any of these drugs

Notify the prescriber immediately — possible pulmonary veno-occlusive disease.

Labs & levels

Test Therapeutic / normal Toxic / critical

Liver aminotransferases (ALT, AST) and bilirubin (ERAs) Bosentan: before starting, then monthly (REMS). Macitentan: baseline, then as clinically indicated. — Bosentan: generally avoided if > 3× ULN at baseline; stop if elevated with liver-injury symptoms or bilirubin ≥ 2× ULN

Hemoglobin / hematocrit (ERAs) Bosentan: after 1 and 3 months, then every 3 months. Ambrisentan: before starting, at 1 month, then periodically. Macitentan: before starting, then as clinically indicated. — —

Pregnancy test (ERAs and riociguat, in females of reproductive potential) Before starting; pregnancy must be excluded before the first dose. — —

Blood pressure and heart rate Epoprostenol: standing and supine, closely for several hours after each dose adjustment. Riociguat: at initiation and before each dose increase (up-titrated only if systolic pressure stays above 95 mmHg without hypotension). — —

Nursing considerations

The RN-specific layer — each action paired with the reason it matters.

Before starting (all)

Record baseline blood pressure and heart rate, and screen the medication list for nitrates, other PDE-5 inhibitors, riociguat, and strong CYP3A inhibitors or inducers.

Why: Nitrate, PDE-5 inhibitor and riociguat combinations cause severe hypotension, and CYP3A drugs change levels of several agents.

For an ERA or riociguat in a female of reproductive potential, confirm a negative pregnancy test before the first dose.

Why: Boxed warning — pregnancy must be excluded before treatment starts.

For an ERA, obtain baseline liver aminotransferases and hemoglobin.

Why: ERAs can injure the liver and lower hemoglobin; bosentan should generally be avoided if baseline aminotransferases exceed 3× ULN.

Endothelin receptor antagonists (bosentan, ambrisentan, macitentan)

Counsel on effective contraception before, during and for one month after treatment, and on emergency contraception after unprotected sex or contraceptive failure.

Why: Embryo-fetal toxicity boxed warning; the labels direct this counseling.

Bosentan: confirm REMS enrollment, draw aminotransferases monthly, and do not rely on hormonal contraception alone.

Why: Bosentan is available only through the REMS because of hepatotoxicity, and it lowers hormonal-contraceptive levels.

Weigh the patient and check for edema; report rapid weight gain or worsening swelling.

Why: Fluid retention can develop within weeks and may need diuretics or hospitalization for decompensated heart failure.

Ambrisentan tablets are swallowed whole — not split, crushed or chewed.

Why: Label administration instruction.

PDE-5 inhibitors (sildenafil, tadalafil)

Ask every patient about nitroglycerin or other nitrates (including as-needed use) before giving a dose.

Why: Organic nitrates in any form, regularly or intermittently, are contraindicated.

Teach patients not to take Viagra, Cialis or any other PDE-5 inhibitor in addition.

Why: Sildenafil is also sold as Viagra and tadalafil as Cialis; taking them with another PDE-5 inhibitor has not been studied.

Tadalafil: give the daily dose all at once rather than divided; shake Tadliq suspension well for 30 seconds before measuring.

Why: Dividing the dose over the day is not recommended; the suspension label requires shaking.

Riociguat

Monitor for hypotension (dizziness, lightheadedness) when starting and with each dose change.

Why: Riociguat lowers blood pressure; the label raises the dose only while systolic pressure stays above 95 mmHg with no signs of hypotension.

Give antacids at least 1 hour apart from riociguat; tablets may be crushed and mixed with water or soft food for patients who cannot swallow them.

Why: Antacids reduce riociguat absorption; the label permits crushing.

Ask about smoking and report if the patient starts or stops.

Why: Riociguat levels are 50–60% lower in smokers, and a dose decrease may be needed after stopping smoking.

Epoprostenol (continuous IV infusion)

Give by continuous infusion through a central venous catheter with an ambulatory pump (peripheral IV only temporarily until central access is placed), using an infusion set with an in-line filter.

Why: Chronic delivery is via a permanent central line; the label specifies the filter.

Reconstitute only with Sterile Water for Injection or 0.9% sodium chloride, never mix with other drugs or solutions, and use strict aseptic technique; protect the solution from direct sunlight.

Why: Epoprostenol is stable only as directed, and aseptic technique lowers the infection risk.

Make sure a backup pump and infusion sets are always available, and never stop or turn down the infusion except on a prescriber’s direction or in a life-threatening situation.

Why: Interruptions in drug delivery can cause rebound pulmonary hypertension — a death has been attributed to one.

After any dose change, monitor standing and supine blood pressure and heart rate closely for several hours.

Why: Epoprostenol is a potent pulmonary and systemic vasodilator.

Treprostinil (subcutaneous/IV, inhaled, oral)

Infusion: subcutaneous is preferred; IV runs through a surgically placed central line. Expect and manage site pain and reaction with subcutaneous delivery.

Why: IV infusion carries the risk of bloodstream infection and sepsis; site pain and reaction are the most common subcutaneous effects.

If an infusion is interrupted, restart it promptly — within a few hours it can usually resume at the same rate; longer gaps may need re-titration.

Why: Abrupt withdrawal can worsen PAH.

Inhaled (Tyvaso): use only with its own inhalation system, in four sessions about 4 hours apart during waking hours; do not mix with other drugs, avoid skin or eye contact, and do not swallow the solution. Tyvaso DPI inhaler is kept dry — never rinsed or washed.

Why: Label administration and device-care instructions.

Oral (Orenitram): give with food and swallow whole — do not crush, split or chew; never stop it abruptly.

Why: Label instructions; abrupt discontinuation can worsen PAH.

Patient teaching

Report symptoms of liver injury — nausea, vomiting, fever, abdominal pain, jaundice, dark urine or unusual fatigue — right away (ERAs).

Why: ERAs can cause hepatotoxicity and liver failure.

Seek emergency care for sudden loss of vision or hearing, or an erection lasting more than 4 hours (PDE-5 inhibitors).

Why: NAION can cause permanent vision loss; priapism needs urgent treatment.

Never run out of a prostacyclin, carry backup supplies, and report fever or redness at the catheter site immediately.

Why: Interruption causes rebound pulmonary hypertension, and line infections can be fatal.

Rise slowly and report dizziness or lightheadedness.

Why: These drugs lower systemic blood pressure.

Common questions

What are Pulmonary Hypertension Agents used for?

Pulmonary Hypertension Agents are used for pulmonary arterial hypertension. Bosentan and sildenafil for PAH in children. Riociguat for chronic thromboembolic pulmonary hypertension that persists or recurs after surgery or is inoperable. Inhaled treprostinil for pulmonary hypertension associated with interstitial lung disease. Treprostinil infusion for patients with PAH who need to transition from epoprostenol.

How do Pulmonary Hypertension Agents work?

They either block the vessel-tightening signal (endothelin) or boost the vessel-relaxing signals (nitric oxide–cGMP and prostacyclin) in the lung arteries.

What are the serious side effects of Pulmonary Hypertension Agents?

Watch for fetal harm with bosentan, ambrisentan, macitentan and riociguat — all are contraindicated in pregnancy; bosentan can raise liver aminotransferases and cause liver failure, so it is available only through the Bosentan REMS; sildenafil, tadalafil, riociguat, epoprostenol and treprostinil dilate systemic vessels and lower blood pressure — lightheadedness, dizziness, chest pain.

When should a nurse hold Pulmonary Hypertension Agents, and what safety checks apply?

Bosentan — ALT/AST elevation with symptoms of liver injury (nausea, vomiting, fever, abdominal pain, jaundice, unusual lethargy or fatigue) or bilirubin ≥ 2× ULN: hold and notify — the label says to discontinue bosentan. Positive pregnancy test or suspected pregnancy on an ERA or riociguat: hold and notify — the drug is discontinued as soon as possible when pregnancy is detected. A prostacyclin infusion stops — pump alarm, occlusion, empty reservoir, broken or dislodged catheter: restore delivery immediately (backup pump and supplies) and notify the prescriber — never leave it off. Fever, chills or signs of infection in a patient with a central line for a prostacyclin: notify the prescriber immediately — possible catheter-related bloodstream infection or sepsis. Sudden loss of vision or hearing, or an erection lasting more than 4 hours, on a PDE-5 inhibitor: seek immediate medical attention (label instruction) and notify the prescriber. New pulmonary edema (worsening dyspnea, crackles, hypoxemia) after starting any of these drugs: notify the prescriber immediately — possible pulmonary veno-occlusive disease.

What labs should be monitored with Pulmonary Hypertension Agents?

Monitor liver aminotransferases (ALT, AST) and bilirubin (ERAs), hemoglobin / hematocrit (ERAs), pregnancy test (ERAs and riociguat, in females of reproductive potential), and blood pressure and heart rate.

Sources

Reviewed by Hae Suk Lee, RN

Educational summary for nursing students. Always verify against current prescribing information and your institution's protocols before administering. Not medical advice.