Practical Considerations for the Pharmacotherapy of Pulmonary Arterial Hypertension (original) (raw)
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Medical treatment update on pulmonary arterial hypertension
Therapeutic advances in chronic disease, 2015
Pulmonary arterial hypertension is a chronic, progressive disease of the pulmonary vasculature resulting in poor outcomes if left untreated. The management of group 1 pulmonary arterial hypertension has included the use of prostanoids, phosphodiesterase-5 inhibitors, and endothelin receptor antagonists targeting the prostacyclin, endothelin-1, and nitric oxide pathways. Three new medications have been approved by the US Food and Drug Administration over the past couple of years. Macitentan is the newest endothelin receptor antagonist, riociguat is a soluble guanylate cyclase stimulator, and treprostinil diolamine is the first oral prostanoid. This review will focus on the key trials leading to their approval, special considerations for each medication, and their potential place in therapy. The use of combination therapy as initial therapy in pulmonary arterial hypertension will also be discussed.
The Current Treatments Of Pulmonary Arterial Hypertension
2020
Pulmonary hypertension is a debilitating chronic disease. In the last 20 years, there has been impressive progress in the treatment strategy of pulmonary arterial hypertension. This led to a significant increase in the awareness and improvement in the clinical outcome, though there was no substantial improvement in the rate of mortality. This review summarizes the current state of the art of the treatment of pulmonary arterial hypertension, including the three main categories of pulmonary hypertension specific medication which were introduced in the last 20 years. Mainly drugs that restore prostaglandins function of the endothelial cells, drugs that restore Cyclic GMP in the endothelial cells and various forms of medication that inhibit Endothelin receptors. The current strategy to treat patients with pulmonary arterial hypertension is to initiate drug therapy as early as possible and to adopt combinational therapy using two or more classes of drugs simultaneously. There are current efforts to introduce future medication that can be more specific to a phenotype of pulmonary hypertension.
Therapeutic Strategies in Pulmonary Arterial Hypertension
European Cardiology Review, 2012
Pulmonary arterial hypertension (PAH) is a serious and life-threatening condition for which the prognosis remains poor. Treatment options include endothelial receptor antagonists, phosphodiesterase (PDE5) inhibitors and prostanoids. Despite all demonstrating good short-term efficacy, none of the currently available drug therapies are curative. Treatment with prostanoids is complex and requires careful monitoring and management through a specialist centre. Furthermore, clinical efficacy is dependent on adequate up-titration of the drug. Treatment should be individualised and modified according to clinical response, with the addition of other therapies if required. The importance of monitoring and modifying therapeutic regimes is discussed. There appears to be reluctance among patients and physicians to employ prostanoid therapy, though an aggressive first-line therapy may be appropriate in advanced cases.
Phosphodiesterase inhibitors for the treatment of pulmonary hypertension
European Respiratory Journal, 2008
The pulmonary vascular bed is both a source of and target for a number of vasoactive factors. Among the most important for pulmonary vascular homeostasis are factors that utilise cyclic guanosine monophosphate (cGMP) as an intracellular second messenger. These include nitric oxide and the natriuretic peptide family (atrial, brain and C-type natriuretic peptides). In the search for therapeutic strategies that engage the cGMP signalling pathway for the treatment of pulmonary arterial hypertension (PAH), inhibition of cGMP metabolism by phosphodiesterase type 5 (PDE5)-targeted compounds has proven most successful to date. One PDE5 inhibitor, sildenafil, has been shown to improve pulmonary haemodynamics and exercise capacity in patients with PAH and is now an approved treatment. Others are under investigation. An interesting, although still tentative, observation is the potential of sildenafil to reduce pulmonary vascular resistance without adversely affecting ventilation-perfusion matching. Another is the expression of phosphodiesterase type 5 in the hypertrophied right ventricle. These data suggest that phosphodiesterase type 5 inhibitors may have effects that distinguish them from other treatments for pulmonary hypertension and merit further study.
New Insights in the Treatment Strategy for Pulmonary Arterial Hypertension
Cardiovascular Drugs and Therapy, 2006
Recent advances in our understanding of the pathophysiological and molecular mechanisms involved in pulmonary arterial hypertension have led to the development of novel and rational pharmacological therapies. In addition to conventional therapy (i.e., supplemental oxygen and calcium channel blockers), prostacyclin or endothelin receptor antagonists have been recommended as a first-line therapy for pulmonary arterial hypertension. However, these treatments have potential limitations with regard to their long-term efficacy and improvement in survival. Furthermore, intravenous prostacyclin (epoprostenol) therapy, which is recommended by most experts for patients with New York Heart Association (NYHA) functional class IV, is complicated, uncomfortable for patients, and expensive because of the cumbersome administration system. Considering these circumstances, it is necessary to develop additional novel therapeutic approaches that target the various components of this multifactorial disease. In this short review, we present an overview of the current treatment options for pulmonary arterial hypertension and describe a case report with primary pulmonary hypertension. A male patient with NYHA functional class IV and showing no response to calcium channel blockers and prostacyclin exhibited significantly improved exercise tolerance and hemodynamics and long-term survival for more than 2.5 years after receiving an oral combination therapy of a phosphodiesterase type 5 inhibitor (sildenafil), phosphodiesterase type 3 inhibitor (pimobendan), and nicorandil. We also discuss the background and plausible potential mechanisms involved in this case, as well as future perspectives in the treatment of pulmonary arterial hypertension.
Current Pharmacological Treatment of Pulmonary Arterial Hypertension
Current Clinical Pharmacology, 2008
Pulmonary arterial hypertension (PAH) is a disease characterized by an elevation in pulmonary artery pressure that can lead to right ventricular failure and death. Conventional treatment is based on non-specific drugs (warfarin, oxygen, diuretics). Pure vasodilators like calcium channel antagonists have little or no effect on the vast majority of patients. Although there is no cure for PAH, newer medical therapies have been shown to improve a variety of clinically relevant end-points including survival, functional class, exercise tolerance, haemodynamics, echocardiographic parameters and quality of life measures. Intravenous prostacyclin, was the first introduced drug for treatment of PAH and remains the first-line treatment for the most severe patients. Since then the list of approved drugs for PAH has expanded to include prostacyclin analogues with differing routes of administration, a dual endothelin receptor antagonist, and a phosphodiesterase-5 inhibitor. Novel drugs have also shown promise in experimental trials and are likely to be added to the list of options. This article reviews the current treatments strategies for PAH.
Management Of Pulmonary Arterial Hypertension: A Brief Overview
2017
PAH is a progressive disease characterized by increased pulmonary vascular resistance, leading to chronic elevation in pulmonary arterial pressure resulting from restricted flow through the pulmonary arterial circulation. Various genetic mutations involving BMPR2, activin-like kinase type-1 receptor are associated with it. Treatment of PAH includes conventional treatments, and disease-specific treatments along with lifestyle modifications. Goals of treatment include alleviation of symptoms, with improvements in quality of life and survival. Several approved agents include prostacyclin and prostacyclin analogues, phosphodiesterase-5 inhibitors, soluble guanylyl cyclase stimulator, endothelin receptor antagonists. Currently, three drug classes have been US FDA-approved for chronic treatment of PAH: prostacyclin analogs, endothelin receptor antagonists (ERAs) and phosphodiesterase type 5 (PDE5) inhibitors. Due to a lack of convenient, effective treatments available for PH, new treatmen...
Therapeutic advances in pulmonary arterial hypertension
Therapeutic advances in respiratory disease, 2008
Pulmonary arterial hypertension (PAH) is characterized by vasoconstriction, in situ thrombosis, and vascular remodeling of small pulmonary arteries inducing increased pulmonary arterial resistance. Conventional treatment is based on life style modification and nonspecific treatment (warfarine, diuretics, oxygen). Calcium channel blockers are vasodilatators that have been shown to be of great efficacy in a very specific subpopulation of patients with PAH. For the majority of patients, specific PAH therapies are still lacking. Numerous studies evaluating prostacyclin agonists, endothelin-receptor antagonists, and phosphodiesterase type 5 inhibitors are now available to guide therapeutic choices. Despite those important advances there is still no cure for PAH. Fortunately, research is ongoing and many drugs show promises.
Targeted therapies in pulmonary arterial hypertension
Pharmacology and Therapeutics, 2014
a b s t r a c t a r t i c l e i n f o Keywords: Endothelial dysfunction Pulmonary arterial hypertension Prostacyclin Endothelin receptor antagonist Type 5 phosphodiesterase inhibitors Kinase inhibitors
American Journal of Cardiovascular Drugs, 2014
Pulmonary arterial hypertension (PAH) is a devastating life-threatening disorder characterized by elevated pulmonary vascular resistance leading to elevated pulmonary arterial pressures, right ventricular failure, and ultimately death. Vascular endothelial cells mainly produce and secrete endothelin (ET-1) in vessels that lead to a potent and long-lasting vasoconstrictive effect in pulmonary arterial smooth muscle cells. Along with its strong vasoconstrictive action, ET-1 can promote smooth muscle cell proliferation. Thus, ET-1 blockers have attracted attention as an antihypertensive drug, and the ET-1 signaling system has paved a new therapeutic avenue for the treatment of PAH. We outline the current understanding of not only the pathogenic role played by ET-1 signaling systems in the pathogenesis of PH but also the clinical pharmacology of endothelin receptor antagonists (ERA) used in the treatment of PAH.