Pulmonary artery hypertension

AHF acute heart failure, CHF chronic heart failure, CRF chronic renal failure, NEP neutral endopeptidase, ECE endothelin converting enzyme, PAH pulmonary arterial hypertension. 

Pulmonary arterial hypertension (PAH) For the treatment of PAH in patients with New York Heart Association (NYHA) Class II to IV symptoms to diminish symptoms associated with exercise. 

Syncope Because of the risk of syncope, monitor vital signs while initiating iloprost. In patients with low systemic blood pressure, take care to avoid further hypotension. Do not initiate iloprost in patients with systolic blood pressure less than 85 mm Hg. Be alert to the presence of concomitant conditions or drugs that might increase the risk of syncope. Syncope can also occur in association with pulmonary arterial hypertension, particularly in association with physical exertion. 

The synthetic analogues of prostacyclin, be-raprost, treprostinil and iloprost, although also platelet aggregation inhibitors, are used to treat pulmonary arterial hypertension. 

Another HMG-CoA reductase inhibitor, benfluorex (structurally an amphetamine), and its D enantiomer, dexfenfluramine, have been withdrawn after several serious pulmonary arterial hypertension cases (Figure 8.59). 

Mechanism of Action An antihypertensive that blocks endothelin-l, the neurohormone that constricts pulmonary arteries. Therapeutic Effect Improves exercise ability and slows clinical worsening of pulmonary arterial hypertension (PAH). Pharmacokinetics Highlybound to plasma proteins, mainlyalbumin. Metabolized in the liver. Eliminated by biliary excretion. Half-life Approximately 5 hr. 

Mechanism of Action An antiplatelet that directly dilates pulmonary and systemic arterial vascular beds, inhibiting platelet aggregation. Therapeutic Effect Reduces symptoms of pulmonary arterial hypertension associated with exercise. Pharmacokinetics Rapidly, completely absorbed after subcutaneous infusion 91% bound to plasma protein. Metabolized by the liver. Excreted mainly in the urine with a lesser amount eliminated in the feces. Half-life 2-4 hr... 

Pulmonary arterial hypertension Continuous Subcutaneous Infusion, IV Infusion... 

Abrupt withdrawal or sudden large reductions in dosage may result in worsening of pulmonary arterial hypertension symptoms. 

Example 7.3 Bosentan therapy in pulmonary arterial hypertension... 

These drugs have also been studied for possible use in other conditions. Clinical studies show distinct benefit in some patients with pulmonary arterial hypertension, and possible benefit in systemic hypertension, cystic fibrosis, and benign prostatic hyperplasia. Preclinical studies suggest that sildenafil may be useful in preventing apoptosis and cardiac remodeling after ischemia and reperfusion. 

Oral 20 (approved for use in pulmonary arterial hypertension), 25, 50, 100 mg tablets Tadalafil (Cialis)... 

Galie N et al Sildenafil citrate therapy for pulmonary arterial hypertension. N Engl 3 Med 2005 353 2148. [PMID 16291984]... 

Dupuis J, Hoeper MM Endothelin receptor antagonists in pulmonary arterial hypertension. Eur Respir J 2008 31 407. [PMID 18238950]... 

Opitz CF et al Inhibition of endothelin receptors in the treatment of pulmonary arterial hypertension Does selectivity matter Eur Heart J 2008 29 1936. [PMID 18562303]... 

Steiropoulos P, Trakada G, Bouros D Current pharmacological treatment of pulmonary arterial hypertension. Curr Clin Pharmacol 2008 3 11. [PMID 18690874]... 

Inhaled NO has also been shown to improve cardiopulmonary function in adult patients with pulmonary artery hypertension. 

In a double-blind, placebo-controlled study, the Bosentan Randomized trial of Endothelin Antagonist Therapy for Pulmonary Arterial I lypertension (BREATHE-2), 33 patients took epoprostenol (2 ng/kg/ min initially, increasing to a mean dosage of 14 ng/kg/min at week 16) and were then randomized for 16 weeks in a 2 1 ratio to bosentan (62.5 mg bd for 4 weeks then 125 mg bd) or placebo (11). There was a non-significant trend towards hemodynamic and clinical improvement with to the combination. There were several early and late major complications (four withdrawals with bosentan + epoprostenol two deaths due to cardiopulmonary failure, one clinical worsening, and one increase in hepatic transaminases and one withdrawal due to increased hepatic transaminases with placebo + epoprostenol. Power was the major limitation of this study, in which only 33 patients were enrolled, and the results should be interpreted with caution. Additional information is needed to evaluate the benefit to harm balance of combined bosentan + epoprostenol therapy in pulmonary arterial hypertension. 

Myers SA, Ahearn GS, Selim MA, Tapson VF. Cutaneous findings in patients with pulmonary arterial hypertension receiving long-term epoprostenol therapy. J Am Acad Dermatol 2004 51 98-102. 

Ivy DD, Doran A, Clausen L, Bingaman D, Yetman A. Weaning and discontinuation of epoprostenol in children with idiopathic pulmonary arterial hypertension receiving concomitant bosentan. Am J Cardiol 2004 93 943-6. 

Humbert M, Barst RJ, Robbins IM, Channick RN, Galie N, Boonstra A, Rubin LJ, Horn EM, Manes A, Simonneau G. Combination of bosentan with epoprostenol in pulmonary arterial hypertension BREATHE-2. Eur Respir J 2004 24 353-9. 

Endothelin Antagonists for the Treatment of Pulmonary Arterial Hypertension... 

J. K., Williams, R. Nodular transformation of the hver associated with portal and pulmonary arterial hypertension. Gastroenterology 1993 104 616 - 621... 

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