Bosentan for Treatment of Pediatric Idiopathic Pulmonary Arterial Hypertension: State-of-the-Art

Wang, Yuchen; Chen, Selena; Du, Junbao

doi:10.3389/fped.2019.00302

Cited by 9 publications

(10 citation statements)

References 49 publications

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“…In European Medicines Agency (EMA), Food and Drug Administration (FDA), and China Food and Drug Administration (CFDA) emphasize that bosentan is recommended for the treatment of PAH to improve effort tolerance and symptoms in patients with WHO functional class III. The effectiveness has been demonstrated in primary PAH (idiopathic and familial), PAH secondary to scleroderma without signifi cant interstitial pulmonary disease, congenital systemic-to-pulmonary shunts, and Eisenmenger syndrome 4 .…”

Section: Discussionmentioning

confidence: 99%

Pulmonary Hypertension in Children - New Insights of Diagnosis and Management

Ina

Rodoman

Palega

et al. 2021

Romanian Journal of Cardiology

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Pulmonary hypertension (PH) is a pathophysiological condition that includes multiple clinical situations and can complicate most cardiovascular and respiratory diseases1. Step by step diagnosis and reviewing contemporary treatment approaches would signifi cantly impact the prognosis of pediatric patients with PH. Management of children with PH requires a multidisciplinary team with experience. PH is frequently associated with cardiac and pulmonary diseases with chronic hypoxia, obstructive respiratory disorders, chest malformations, pneumonia, acute respiratory distress, and can also develop during late phases of cystic fi brosis, bronchial asthma, bronchiectasis. Updated defi nition of PH at the world symposium (HTAP, Nice, 2018) includes values of pulmonary artery pressure >20 mmHg and using pulmonary vascular resistance (PVR) indexed to the body surface to identify pre-capillary PH, PVR≥3 WU×m2 5. Cardiac catheterization represents the gold standard in diagnosing PH, being the most precise method of measuring the blood pressure (BP) in the pulmonary artery and offering valuable information about cardiac output, arterial pressure, and the response to pulmonary vasodilators2,3. The specifi c modern treatment with endothelin receptor inhibitors signifi cantly improves the disease’s clinical course and brings better parameters at instrumental investigations.

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Section: Discussionmentioning

confidence: 99%

Pulmonary Hypertension in Children - New Insights of Diagnosis and Management

Ina

Rodoman

Palega

et al. 2021

Romanian Journal of Cardiology

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“…The pharmacokinetics of bosentan in pediatric pulmonary arterial hypertension and healthy adults are similar [ 92 ]. Studies have shown that the exposure plateau for bosentan is reached at a dose of 2 mg/kg twice daily, making the adequate dose up to 4 mg/kg [ 97 ].…”

Section: Drugs For Chd Treatmentmentioning

confidence: 99%

Congenital Heart Disease: The State-of-the-Art on Its Pharmacological Therapeutics

Varela-Chinchilla

Sánchez-Mejía

Trinidad-Calderón

2022

JCDD

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Congenital heart disease is one of the most common causes of death derived from malformations. Historically, its treatment has depended on timely diagnosis and early pharmacological and surgical interventions. Survival rates for patients with this disease have increased, primarily due to advancements in therapeutic choices, but mortality remains high. Since this disease is a time-sensitive pathology, pharmacological interventions are needed to improve clinical outcomes. Therefore, we analyzed the applications, dosage, and side effects of drugs currently used for treating congenital heart disease. Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, and potassium-sparing diuretics have shown a mortality benefit in most patients. Other therapies, such as endothelin receptor antagonists, phosphodiesterase-5 inhibitors, prostaglandins, and soluble guanylyl cyclase stimulators, have benefited patients with pulmonary artery hypertension. Likewise, the adjunctive symptomatic treatment of these patients has further improved the outcomes, since antiarrhythmics, digoxin, and non-steroidal anti-inflammatory drugs have shown their benefits in these cases. Conclusively, these drugs also carry the risk of troublesome adverse effects, such as electrolyte imbalances and hemodynamic compromise. However, their benefits for survival, symptom improvement, and stabilization outweigh the possible complications from their use. Thus, cases must be assessed individually to accurately identify interventions that would be most beneficial for patients.

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“…Endothelin-1 is highly expressed in the lung and the over-activation of ET A receptors and the reduced ET B receptors activity result in intense vasoconstriction with matrix production and cell proliferation. These changes lead to fibrosis and inflammation of pulmonary artery and plasma values of ET-1 correlate with pulmonary vascular resistance levels [ 18 ].…”

Section: Endothelin Et-1mentioning

confidence: 99%

“…The damage of vascular endothelial function induced by increased plasma levels of ET-1 is one of the key factors in the pathogenesis of Idiopathic Pulmonary Arterial Hypertension and, although this is not part of the scope of our review, it is useful to remember that the use of ET receptor antagonists in this setting has greatly helped in understanding the interaction between ET and NO in humans [ 18 ]. While bosentan, a competitive antagonist of ET A and ET B receptors, has already been listed by the US Food and Drug Administration as an indication in children 3 years old and older with Idiopathic or Congenital Pulmonary Artery Hypertension [ 18 ], the use of this class of drugs for arterial hypertension should be limited to specific patients, such as adults with treatment-resistant hypertension or chronic kidney disease in whom the benefits outweigh the risks including the described hepatotoxicity, fluid retention, gonadal toxicity, and potential for teratogenicity [ 34 ]. Ongoing trials with ET receptor antagonists in focal glomerulosclerosis, IgA nephropathy, and resistant hypertension hold promise for an approved indication for ET receptor antagonists in treating kidney disease [ 35 , 36 ]; nevertheless, their use in children is far from being considered for these indications.…”

Section: Endothelin-1 Nitric Oxide and Hypertension In Children And A...mentioning

confidence: 99%

Relationship between endothelin and nitric oxide pathways in the onset and maintenance of hypertension in children and adolescents

et al. 2021

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The mechanisms that regulate blood pressure are numerous and complex; one mechanism that plays an important role in this scenario is represented by the balance between the vasoconstrictor effect of endothelin-1 and the vasodilator effect of nitric oxide. While there is agreement on the fact that increased endothelin-1 activity and decreased nitric oxide bioavailability are present in hypertensive adults, the situation is less clear in children and adolescents. Not all studies agree on the finding of an increase in plasma endothelin-1 levels in hypertensive children and adolescents; in addition, the picture is often confused by the concomitant presence of obesity, a condition that stimulates the production of endothelin-1. Furthermore, there is recent evidence that, in younger obese and hypertensive subjects, there is an overproduction of nitric oxide, rather than a reduction. This condition may change over time, causing endothelial dysfunction due to a reduced availability of nitric oxide in hypertensive adolescents. The purpose of this review is to address the main biochemical and pathophysiological aspects of endothelin and nitric oxide involvement in hypertension and to summarize the available scientific evidence on their role in the onset and maintenance of high blood pressure in children and adolescents.

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Bosentan for Treatment of Pediatric Idiopathic Pulmonary Arterial Hypertension: State-of-the-Art

Cited by 9 publications

References 49 publications

Pulmonary Hypertension in Children - New Insights of Diagnosis and Management

Pulmonary Hypertension in Children - New Insights of Diagnosis and Management

Congenital Heart Disease: The State-of-the-Art on Its Pharmacological Therapeutics

Relationship between endothelin and nitric oxide pathways in the onset and maintenance of hypertension in children and adolescents

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