Drugs Used in Pulmonary Hypertension

Drugs Used in Pulmonary Hypertension

Drugs Used in Pulmonary Hypertension

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PH Unmasked - The Battle Plan

Pulmonary Hypertension (PH): Mean Pulmonary Arterial Pressure (mPAP) $\ge$ 25 mmHg. WHO Classification Summary (Focus: Group 1 PAH):

  • Group 1: PAH (Idiopathic, Heritable, Drug-induced, CTD-APAH)
  • Other groups: Left heart, Lung disease/hypoxia, CTEPH, Unclear. Key Pathogenic Pathways (📌 Target "PEN"):
  • Prostacyclin (↓PGI₂): Vasodilation. Drugs: Epoprostenol, Selexipag.
  • Endothelin (↑ET-1): Vasoconstriction. Drugs: Bosentan, Ambrisentan.
  • NO-cGMP (↓NO): Vasodilation. Drugs: Sildenafil, Riociguat. Pulmonary Hypertension Therapeutic Targets

⭐ Most PAH-specific drugs target Group 1 WHO classification of pulmonary hypertension (PAH).

Prostacyclin Parade - Dilators Deluxe

  • MOA: PGI₂ analogs & IP receptor agonists → $↑cAMP$ → vasodilation, anti-proliferative, anti-platelet effects.
  • Key Class ADRs: Flushing, headache, jaw pain, diarrhea, hypotension. Infusion site pain (Treprostinil SC).
DrugRoute(s)Half-life (approx.)Notes
EpoprostenolIV (continuous)3-5 minRequires central line
IloprostInhaled (6-9/day), IV20-30 minFrequent inhalation
TreprostinilIV, SC, Inhaled, Oral4 hrsVersatile routes
SelexipagOral (prodrug)~10-14 hrs (active)Oral non-prostanoid IP agonist

Endothelin Enders - Squeezing Stoppers

ERAs block endothelin pathway: ↓vasoconstriction, ↓proliferation. 📌 BAM: Bosentan, Ambrisentan, Macitentan.

  • MOA:

    • Bosentan/Macitentan: Non-selective ET-A & ET-B blockers.
    • Ambrisentan: Selective ET-A blocker.
    • Effect: ↓Pulmonary Vascular Resistance (PVR), ↓smooth muscle proliferation.
  • Key ADRs:

    • ⚠️ Hepatotoxicity (Bosentan highest risk; LFTs monitoring).
    • ⚠️ Teratogenicity (All ERAs - REMS program mandatory).
    • Edema, anemia, headache.
  • Comparison of ERAs:

    ERAReceptor SelectivityHepatotoxicity RiskKey DDI
    BosentanET-A & ET-BHighCYP inducer (e.g. ↓warfarin)
    AmbrisentanSelective ET-ALowMinimal
    MacitentanET-A & ET-BLowCYP3A4 substrate

⭐ All ERAs are potent teratogens (contraindicated in pregnancy); REMS program mandatory due to severe birth defect risk.

NO-Go Zone - Relaxers United

Drugs enhancing NO-cGMP signaling for pulmonary vasodilation.

  • PDE-5 Inhibitors: Sildenafil, Tadalafil
    • MOA: Inhibit PDE-5 → ↓$cGMP$ degradation → ↑$cGMP$ levels → vasodilation.
    • ADRs: Headache, flushing, hypotension. Sildenafil: visual disturbances (cyanopsia). 📌 "Sildena-FILls vision blue".
    • ⚠️ Contraindication: Nitrates (risk of severe hypotension).
  • sGC Stimulators: Riociguat
    • MOA: Directly stimulates soluble guanylate cyclase (sGC) → ↑$cGMP$ production → vasodilation.
    • ADRs: Headache, dizziness, hypotension.
    • ⚠️ Contraindication: Nitrates, PDE-5 inhibitors.

⭐ Sildenafil and other PDE-5 inhibitors are absolutely contraindicated with nitrates due to the risk of profound, life-threatening hypotension.

PAH Pals - The Sidekicks

  • Calcium Channel Blockers (CCBs):
    • Strictly for acute vasoreactivity test (AVT) responders (approx. 10-15% of IPAH).
    • High doses (e.g., nifedipine, diltiazem) are essential for efficacy.
  • Anticoagulants (e.g., Warfarin):
    • Rationale: Counteract prothrombotic state, preventing in-situ thrombosis and thromboembolism.
  • Diuretics (e.g., Furosemide):
    • Key for managing fluid overload and symptoms of Right Heart Failure (RHF).
  • Oxygen Therapy:
    • Crucial for patients with hypoxemia; aim to maintain $SaO_2$ > 90%.
  • General Approach:
    • Supportive therapies are vital adjuncts. Combination with targeted drugs is standard.

⭐ For patients with PAH, particularly idiopathic PAH, anticoagulation with warfarin is often considered to address the presumed hypercoagulable state and risk of thrombosis.

High‑Yield Points - ⚡ Biggest Takeaways

  • Prostacyclin analogues (Epoprostenol, Iloprost) are potent vasodilators & anti-proliferative; Epoprostenol has a short half-life.
  • Endothelin receptor antagonists (Bosentan, Ambrisentan) block vasoconstrictor ET-1; Bosentan is hepatotoxic.
  • PDE-5 inhibitors (Sildenafil, Tadalafil) ↑cGMP for pulmonary vasodilation; avoid with nitrates.
  • Riociguat, an sGC stimulator, is used for PAH and CTEPH.
  • High-dose CCBs (Nifedipine) are for vasoreactive PAH patients only, post-vasoreactivity testing.
  • Selexipag is an oral IP prostacyclin receptor agonist.

Practice Questions: Drugs Used in Pulmonary Hypertension

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Flashcards: Drugs Used in Pulmonary Hypertension

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Cardiovascular (Antihypertensives) _____ and angiotensin II receptor blockers are first line treatment for hypertension in patients with heart failure, MI, and/or diabetes

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Cardiovascular (Antihypertensives) _____ and angiotensin II receptor blockers are first line treatment for hypertension in patients with heart failure, MI, and/or diabetes

ACE inhibitors

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