Group 4 Pulmonary Hypertension Medication

Updated: Mar 16, 2020
  • Author: Paresh Chandra Giri, MD, FCCP; Chief Editor: Zab Mosenifar, MD, FACP, FCCP  more...
  • Print
Medication

Medication Summary

The goals of pharmacotherapy are to reduce morbidity and prevent complications.

Next:

Soluble Guanylate Cyclase Stimulators

Class Summary

These agents facilitate the pathways that play a role in vasodilation.

Riociguat (Adempas)

Riociguat stimulates vasodilation by increasing generation of cyclic guanosine monophosphate (cGMP) as it stimulates the soluble guanylate cyclase-cGMP pathway.

Previous
Next:

Endothelin Receptor Antagonists

Class Summary

Endothelin-receptor antagonists competitively bind to the endothelin-1 receptors EtA and EtB, causing reductions in pulmonary arterial pressure (PAP), pulmonary vascular resistance (PVR), and mean right atrial pressure (RAP).

Bosentan (Tracleer)

Bosentan inhibits vessel constriction and elevation of blood pressure by competitively binding to EtA and EtB receptors in endothelium and vascular smooth muscle. This leads to a significant increase in cardiac index associated with significant reductions in PAP, PVR, and mean RAP.

Macitentan (Opsumit)

Macitentan blocks the binding of endothelin-1 to endothelin receptor subtypes ETa and ETb on smooth muscle and vascular endothelium. The stimulation of these receptors is associated with fibrosis, inflammation, hypertrophy, and vasoconstriction.

Ambrisentan (Letairis)

Ambrisentan improves exercise ability and slows the progression of clinical symptoms. It inhibits vessel constriction and elevation of blood pressure by competitively binding to EtA and EtB receptors in endothelium and vascular smooth muscle. This leads to a significant increase in cardiac index associated with significant reductions in PAP, PVR, and mean RAP.

Previous
Next:

Phosphodiesterase-5 Enzyme Inhibitors

Class Summary

The antiproliferative effects of the phosphodiesterase type 5 (PDE5) pathway, which regulates cGMP hydrolysis, may be significant in the long-term treatment of pulmonary arterial hypertension (PAH) with PDE5 inhibitors.

Sildenafil (Revatio)

Sildenafil promotes selective smooth-muscle relaxation in lung vasculature, possibly by inhibiting PDE5. This results in a subsequent reduction of blood pressure in pulmonary arteries and an increase in cardiac output.

Tadalafil (Adcirca)

Tadalafil is a PDE5 inhibitor indicated for improving exercise capacity in patients with WHO class 1 PAH. It increases cGMP, the final mediator in the nitric oxide pathway.

Previous
Next:

PAH, Prostacyclin Analogs

Class Summary

Prostacyclin is a strong vasodilator of all vascular beds and a potent endogenous inhibitor of platelet aggregation. Platelet effects result from activation of intracellular adenylate cyclase and from increased cyclic adenosine monophosphate (cAMP) concentrations within platelets. Prostacyclin may decrease thrombogenesis and platelet clumping in the lungs by inhibiting platelet aggregation.

Iloprost (Ventavis)

Iloprost is a synthetic analogue of prostacyclin that dilates systemic and pulmonary arterial vascular beds. It is indicated in patients with New York Heart Association class III or IV symptoms to improve exercise tolerance and symptoms and to delay deterioration.

Previous
Next:

Diuretics, Loop

Class Summary

Judicious use of diuretics helps reduce systemic congestion and edema. Conversely, excessive hypovolemia may interfere with tissue oxygenation by lowering cardiac output.

Furosemide (Lasix)

Furosemide increases excretion of water by interfering with the chloride-binding cotransport system, thereby, in turn, inhibiting sodium and chloride reabsorption in the ascending loop of Henle and the distal renal tubule. The dosage must be individualized to the patient. Depending on the response, administer furosemide in increments of 20-40 mg, no sooner than 6-8 hours after the previous dose, until the desired diuresis occurs. When treating infants, titrate with increments of 1 mg/kg until a satisfactory effect is achieved.

Bumetanide (Bumex, Burinex)

Bumetanide increases excretion of water by interfering with the chloride-binding cotransport system; this, in turn, inhibits sodium and chloride reabsorption in the ascending loop of Henle. Bumetanide does not appear to act in the distal renal tubule.

Previous
Next:

Anticoagulants, Hematologic

Class Summary

Long-term anticoagulation with warfarin should be considered in selected patients with secondary PAH. These include patients with chronic pulmonary embolism (PE), pulmonary veno-occlusive disease, and atrial fibrillation induced by left- or right-side heart failure who are at high risk for developing venous thromboembolism (eg, those with cor pulmonale or immobility secondary to severe dyspnea).

Warfarin (Coumadin, Jantoven)

Warfarin interferes with hepatic synthesis of vitamin K–dependent coagulation factors. It is used for prophylaxis and treatment of deep venous thrombosis, PE, and thromboembolic disorders.

Tailor the dose to maintain an international normalized ratio (INR) in the range of 2-3. Recurrence of deep venous thrombosis and PE increases dramatically when the INR drops below 2 and decreases when it is kept between 2 and 3. Serious bleeding risk (including hemorrhagic stroke) is approximately constant when the INR is between 2.5 and 4.5 but rises dramatically when it exceeds 5.

Previous