What anti-hypertension medications are contraindicated in patients with pulmonary hypertension?

Antihypertensive Medications Contraindicated in Pulmonary Hypertension

Nitrates and nitrate-like medications are absolutely contraindicated in patients with pulmonary hypertension who are taking phosphodiesterase type-5 (PDE-5) inhibitors due to the risk of profound systemic hypotension. 1

Key Contraindicated Medications

Absolute Contraindications

• Nitrates when used with PDE-5 inhibitors (sildenafil, tadalafil)
  • Nitroglycerin (all forms: sublingual, patch, spray, IV) 1, 2
  • Isosorbide mononitrate or dinitrate 2
  • Nicorandil 1
  • "Poppers" (amyl nitrate/nitrite) 2

Medications Requiring Caution or Dose Adjustment

• Calcium Channel Blockers (CCBs)

  • Should only be used in vasoreactive PAH patients (approximately 10-15% of cases) 3, 4
  • Non-selective CCBs may worsen right ventricular failure in non-vasoreactive patients 5, 6

• Beta-blockers

  • May worsen right ventricular function and exercise capacity 1, 5
  • Particularly problematic in decompensated right heart failure 1

• ACE inhibitors/ARBs

  • May cause excessive hypotension in PAH patients who are preload-dependent 1, 5
  • Enalaprilat specifically noted to have unpredictable BP response in hypertensive emergencies 1

Drug Interactions with PAH-Specific Medications

Endothelin Receptor Antagonists (ERAs)

• Bosentan interactions:

  • Cyclosporine: Combination contraindicated (bosentan levels increase 4-fold) 1
  • Glibenclamide: Combination contraindicated (increased aminotransferases) 1
  • Fluconazole/amiodarone: Potentially contraindicated (bosentan levels increase) 1

• Sitaxentan interactions:

  • Cyclosporine: Combination contraindicated (increases sitaxentan levels) 1
  • Warfarin: Requires 80% dose reduction of warfarin 1

• Ambrisentan:

  • Requires caution with cyclosporine and ketoconazole 1

PDE-5 Inhibitors

• Sildenafil/Tadalafil:
  • Nitrates: Combination absolutely contraindicated (profound hypotension) 1, 2
  • HIV protease inhibitors: Sildenafil dose adjustments required 1
  • HMG-CoA reductase inhibitors: Possible increased risk of rhabdomyolysis 1

Management Considerations

• Hemodynamic management:

  • Avoid excessive volume loading in PAH patients with right ventricular dysfunction 5
  • Vasopressors and inotropes often preferred over fluid boluses in shock 5

• Diuretics:

  • Indicated in PAH patients with signs of right ventricular failure and fluid retention 1
  • Careful monitoring required to avoid excessive preload reduction 3

• Supportive therapy:

  • Continuous long-term oxygen therapy indicated when arterial blood O₂ pressure is consistently <8 kPa (60 mmHg) 1
  • Oral anticoagulation should be considered in specific PAH subtypes (IPAH, heritable PAH) 1

Special Considerations

• Hypertensive emergencies in PAH patients:

  • Avoid agents that may worsen pulmonary pressures or right heart function 1
  • Clevidipine or nicardipine may be preferred if vasodilation needed 1
  • Careful monitoring required as many IV antihypertensives can worsen right heart failure 5

• PAH with left heart disease:

  • PAH-specific therapies are not recommended in patients with PH due to left heart disease 1
  • Treatment should focus on the underlying left heart condition 4

• Pregnancy:

  • Pregnancy is contraindicated in PAH patients due to high mortality risk 1
  • Hormonal contraceptives may have reduced efficacy with bosentan 1