Respiratory Disorders

Pulmonary Hypertension

Clinical overview and exam mastery guide for PH classification, Group 1 PAH targeted therapy, CTEPH strategy, and right-heart failure support.

Definition
mPAP 20 mmHg or higher
Diagnostic Standard
Right heart catheterization
Main Drug Target Group
WHO Group 1 PAH
Core Pathways
Endothelin, NO, prostacyclin

PAH Therapeutic Pathways

Endothelin ERA blockade less constriction NO-cGMP PDE-5 inhibitor or sGC stimulator Prostacyclin vasodilation antiproliferative Group 1 PAH: combination therapy is common ERA plus PDE-5 inhibitor initial strategy, escalate to prostacyclin when severe

Modern PAH regimens combine targeted pathway therapies.

1. What Is Pulmonary Hypertension (PH)?

Pulmonary hypertension is elevated pressure in pulmonary arteries and is defined by mean pulmonary arterial pressure of 20 mmHg or higher on right heart catheterization.

Right ventricular strain Right heart failure High untreated mortality

2. Classification (WHO Groups)

  • Group 1: Pulmonary arterial hypertension (PAH)
  • Group 2: PH due to left heart disease
  • Group 3: PH due to lung disease/hypoxia
  • Group 4: Chronic thromboembolic PH (CTEPH)
  • Group 5: Multifactorial/unclear mechanisms
  • Targeted PH drugs mainly apply to Group 1

3. Pathophysiology (PAH)

Endothelin Pathway

Excess signaling drives vasoconstriction and remodeling.

Nitric Oxide Pathway

Impaired signaling reduces vasodilation reserve.

Prostacyclin Pathway

Reduced prostacyclin worsens vasoconstriction and proliferation.

PAH pharmacology targets these three pathways directly.

4. Management of Group 1 PAH

Goals are to reduce pulmonary vascular resistance, improve exercise capacity, and delay progression.

Drug Class MOA Major Side Effects Contraindications / Notes
Endothelin receptor antagonists (bosentan, ambrisentan, macitentan) Block endothelin-1 signaling, reducing vasoconstriction and remodeling Hepatotoxicity (especially bosentan), edema, anemia Pregnancy contraindication, severe liver impairment; monthly liver monitoring (especially bosentan)
PDE-5 inhibitors (sildenafil, tadalafil) Inhibit PDE-5, increase cGMP, enhance NO-mediated vasodilation Headache, flushing, hypotension Contraindicated with nitrates and severe hypotension
Prostacyclin analogues (epoprostenol, treprostinil, iloprost) Prostacyclin receptor effect: potent vasodilation, antiproliferative action, reduced platelet aggregation Hypotension, jaw pain, flushing, infusion-site pain IV forms may require continuous infusion; severe disease escalation class
Soluble guanylate cyclase stimulator (riociguat) Directly stimulates sGC, increasing cGMP and vasodilation Hypotension, headache, dyspepsia Pregnancy contraindication; do not combine with PDE-5 inhibitors
Initial PAH strategy often uses combination therapy such as ERA plus PDE-5 inhibitor.

5. Group-Specific Management

Groups 2 and 3

  • Group 2: treat underlying left-sided heart disease
  • Group 3: optimize lung disease and oxygenation

Group 4 (CTEPH)

  • Lifelong anticoagulation
  • Pulmonary endarterectomy when operable
  • Riociguat for selected inoperable/persistent disease

6. Right Heart Failure Management

Diuretics for volume overload Oxygen support Careful preload handling
Avoid overly aggressive preload reduction in unstable right-sided failure.

Management Recap Drill

PAH 1: confirm diagnosis with right heart catheterization.
PAH 2: initiate pathway-targeted therapy (often ERA plus PDE-5 inhibitor).
PAH 3: escalate to prostacyclin therapy for severe/high-risk disease.
PAH 4: monitor toxicity (especially liver function with bosentan).
PAH 5: avoid pregnancy with teratogenic regimens.
CTEPH: anticoagulate and evaluate for surgery.

Visual Algorithm Placeholder

[Insert Pulmonary Hypertension Treatment Pathway Diagram Here During UI Integration]

Guideline References (Management)

ESC/ERS Guidelines for Pulmonary Hypertension

https://www.escardio.org/Guidelines

Guideline Scope

  • Risk stratification
  • Initial combination therapy
  • Escalation to advanced treatment

7. Common Exam Traps

Most targeted PH drugs are for Group 1 PAH, not all PH groups.
ERAs are teratogenic.
Do not combine PDE-5 inhibitors with nitrates.
IV epoprostenol has survival benefit in severe PAH.
Riociguat has a key role in inoperable CTEPH.

8. Quick Revision Summary

Must Remember

  • PH is defined hemodynamically (mPAP 20 mmHg or higher)
  • Five WHO groups, with targeted pharmacology centered on Group 1
  • Three treatment pathways: endothelin, NO-cGMP, prostacyclin
  • Combination therapy is common in PAH
  • Severe disease often requires prostacyclin escalation

Practice Questions Placeholder

  • Topic: Pulmonary Hypertension
  • Subtopics: WHO groups, ERA, PDE-5 inhibitors, prostacyclin, CTEPH management