Abstract:
:Pulmonary arterial hypertension (PAH) is a progressive disease of the pulmonary vasculature characterized by elevated pulmonary artery pressure. Currently, there is no cure for this disease, and treatment is palliative. PAH therapies target 3 main pathways: prostacyclin, endothelin, and nitric oxide. The 3 distinct therapeutic pathways targeted have provided the opportunity to explore the efficacy of combination therapy. This article reviews the pharmacokinetic profiles of available therapies and existing clinical trial results that support combination therapy, as well as provides rationale and clinical guidance for combination therapy. Combination therapy may offer an additive and potentially synergistic benefit. The initiation and titration of combination therapy has several pharmacokinetic considerations, such as the onset of drugs' action and time to steady state, as well as potential drug interactions. Although great strides have been made in the treatment of PAH, unanswered questions still remain in regard to combination therapy: (1) Which combination is best? and (2) Is it most appropriate to maximize one drug and then initiate a second drug or to start both drugs simultaneously? Answers to these questions will help identify a safe and effective combination therapy and thus optimize treatment for patients with PAH.
journal_name
J Cardiovasc Pharmacoljournal_title
Journal of cardiovascular pharmacologyauthors
Gokhman R,Smithburger PL,Kane-Gill SL,Seybert ALdoi
10.1097/FJC.0b013e3181f89bdbsubject
Has Abstractpub_date
2010-12-01 00:00:00pages
686-95issue
6eissn
0160-2446issn
1533-4023journal_volume
56pub_type
杂志文章,评审abstract::Previously we showed that blocking the endothelin (ET)A receptor subtype with BQ-153 inhibited the vasoconstrictor effects of intravenously administered ET-1. In the presence of the ET(A) antagonist, ET-1 produced marked reductions in myocardial contractility and renal blood flow. We postulated that either the ET(B) r...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199706000-00002
更新日期:1997-06-01 00:00:00
abstract::Using micropuncture techniques in euvolemic adult male Munich-Wistar rats, we assessed the functional role of renal beta-adrenoceptors in mediating neural control of glomerular filtration and proximal tubular reabsorption. The determinants of nephron filtration and rate of proximal tubular reabsorption were measured i...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199103000-00007
更新日期:1991-03-01 00:00:00
abstract::We investigated the effect of gallopamil on cardiac sarcoplasmic reticulum (SR) function. Heavy SR was prepared from bovine ventricular muscle. Oxalate-supported calcium uptake was stimulated by gallopamil at concentrations ranging from 10 to 300 nM, whereas higher concentrations were ineffective. Peak stimulation ave...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:1992-01-01 00:00:00
abstract::Angiotensin II AT1-receptor blockers (AT1-s) prolong survival in experimental postischemic (coronary artery ligation) heart failure (CHF) in rats. The goal of this study was to investigate whether potential beneficial effects of short- and/or long-term treatment with AT1-s on coronary dynamics, function, and structure...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-200009000-00008
更新日期:2000-09-01 00:00:00
abstract::As part of the Amlodipine Cardiovascular Community Trial (ACCT), which was a large multicenter study designed to assess the effects of the calcium channel blocker amlodipine besylate (Norvasc) as monotherapy for treatment of mild to moderate hypertension, we sought to determine the effects of amlodipine on regression ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1097/00005344-199509000-00018
更新日期:1995-09-01 00:00:00
abstract::Endothelin-1 (ET-1) is a potent vasoconstrictive peptide produced by endothelial cells of blood vessels. This peptide has quite a unique structure and pharmacological properties. ET-1 is produced in endothelial cells and may be secreted in a similar way to some paracrine hormones. The pressor response of ET-1 is large...
journal_title:Journal of cardiovascular pharmacology
pub_type: 历史文章,杂志文章,评审
doi:10.1097/00005344-198900135-00002
更新日期:1989-01-01 00:00:00
abstract::Ambulatory blood pressure monitoring (ABPM) is a particularly useful method for evaluating the effects of antihypertensive drugs. ABPM allows the therapeutic effect of an agent to be assessed continually by a large number of measurements, and the greater number of readings contributes to the higher degree of reproduci...
journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章
doi:
更新日期:1995-01-01 00:00:00
abstract::Late sodium channel current (late INa) is considered to be an antiarrhythmic target. The prime antiarrhythmic mechanisms of late INa inhibition have been suggested to be (1) suppression of intracellular calcium [Cai]-mediated rhythmic activity (through reduction in Cai secondary to the decrease in intracellular sodium...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:10.1097/FJC.0000000000000510
更新日期:2017-09-01 00:00:00
abstract::We have studied the effects of bremazocine on the peripheral sympathetic nervous system and the arterial blood pressure of pithed rabbits with electrically (2 Hz) stimulated sympathetic outflow, and compared them with the effects of Leu-enkephalin and fentanyl. The 3H-noradrenaline plasma clearance and the plasma conc...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198605000-00005
更新日期:1986-05-01 00:00:00
abstract::It is already well known that alteration of angiotensin II (Ang II) receptors results in cardiac remodeling in different pathological states, and it is believed that Ang II stimulates the release of endothelin-1 (ET-1). The present study aimed at investigating the interaction between ET-1 and different Ang II receptor...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/01.fjc.0000166223.57970.5f
更新日期:2004-11-01 00:00:00
abstract::The selectivity of single oral doses of xamoterol, 200 mg, prenalterol, 50 mg, and salbutamol, 8 mg, was compared in eight healthy male volunteers by measuring their effects on sleeping heart rate, supine heart rate, blood pressure, forearm blood flow, finger tremor, and exercise heart rate in the presence and absence...
journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00005344-198805000-00006
更新日期:1988-05-01 00:00:00
abstract::Glucocorticoids (GCs) are widely used anti-inflammatory drugs well known to cause many adverse effects. Still, there is a dearth of data on the long-term cardiovascular effects of GCs in patients with established cardiovascular disease and the effect on atherosclerotic plaque composition. A total of 1894 patients who ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0000000000000292
更新日期:2015-10-01 00:00:00
abstract::Intracellular pH (pHi) regulation in the heart relies on the activity of three membrane mechanisms: the Na+/H+ exchange and an Na+, HCO3(-)-dependent transport, both activated after an acid load, and the Cl-/HCO(3-) exchange, activated by an intracellular alkalinization. Whereas several specific inhibitors of Na+/H+ e...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199610000-00011
更新日期:1996-10-01 00:00:00
abstract::Hypertension, atherosclerosis, arteriosclerosis, and cardiomyopathy account for 80% of all diabetic deaths. A paucity of data exists concerning reactivity of the diabetic vasculature to vasopressor substances. The purpose of this investigation was to determine the influence of short-term (4-5 weeks) diabetes on the re...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198303000-00016
更新日期:1983-03-01 00:00:00
abstract::T89 (Dantonic) is a modern herbal medicine currently used in Chinese hospitals for the management of ischemic heart disease. This dose-escalation clinical trial aims to assess tolerability of Western people to T89. Healthy Australian adults of non-Asian background orally took a single dosage of 6, 8, 10, 12, 13, 14, 1...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0b013e31826f6179
更新日期:2012-12-01 00:00:00
abstract::Inflammation plays a central role in the pathogenesis of atherosclerosis. This study investigated whether the proteasome inhibitor has the same preventive effect on the formation of accelerated atherosclerosis in rabbits with uremia compared with a NF-kappaB inhibitor. New Zealand white rabbits were subjected to five-...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0b013e3181c87f8e
更新日期:2010-02-01 00:00:00
abstract:BACKGROUND:Prostacyclin mimetics are vasodilatory agents used in the treatment of pulmonary arterial hypertension. The direct effects of prostanoids on right-ventricular (RV) function are unknown. We aimed to investigate the direct effects of prostacyclin mimetics on RV function in hearts with and without RV hypertroph...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0000000000000435
更新日期:2017-01-01 00:00:00
abstract::Flosequinan, a new orally active vasodilator, and its sulfone metabolite were evaluated for inotropic activity in isolated ferret papillary muscles and pentobarbital anesthetized open-chest dogs. In vitro, flosequinan and its sulfone derivative increased tension development in a concentration-dependent manner (1-50 mi...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198909000-00009
更新日期:1989-09-01 00:00:00
abstract::A double-blind randomised, parallel, placebo-controlled study was performed in patients with congestive heart failure, at 13 centres in 10 countries, to assess the efficacy and safety of lisinopril, a new angiotensin-converting enzyme inhibitor. After a 2-week run-in period, 130 patients receiving digoxin and/or diure...
journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00005344-198700003-00021
更新日期:1987-01-01 00:00:00
abstract::The aim of this study was to compare the hemodynamic effects of three nitric oxide (NO) donors [i.e., (+/-)-(E)-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexenamide (FK409), (+/-)-N-[(E)-4-ethyl-3-[(Z)-hydroxyimino]-6-methyl-5-nitro-3-he ptenyl]-3-pyridinecarboxamide (FR 146801) and isosorbide dinitrate (ISDN)] in rats. In...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199708000-00011
更新日期:1997-08-01 00:00:00
abstract::The prognosis for patients with congestive heart failure (CHF) is poor, with a mortality exceeding 50% within 5 years from diagnosis. This poor prognosis remains despite improved pharmacological therapy. Because the prevalence of sudden death among these patients is high, reported to exceed 40%, the prognostic importa...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:
更新日期:1991-01-01 00:00:00
abstract:OBJECTIVE:This study was designed to assess whether angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) could prevent the recurrence of atrial fibrillation (AF). METHODS:A systemic literature search of PubMed, EMBASE, and Cochrane Controlled Trials Register till 2012 was performed...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,meta分析,评审
doi:10.1097/FJC.0b013e3182a094a1
更新日期:2013-10-01 00:00:00
abstract::The present study was designed to investigate the lipid-lowering properties and mechanisms of action of a new HMG-CoA reductase inhibitor, rosuvastatin, in female ApoE*3-Leiden transgenic mice. Mice received a high fat/cholesterol (HFC) diet containing either rosuvastatin (0 [control], 0.00125%, 0.0025%, or 0.005% [w/...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-200501000-00010
更新日期:2005-01-01 00:00:00
abstract::Several antiarrhythmic agents with Na-channel blocking action have been shown to inhibit cardiac K(ATP) channels. We used cibenzoline to examine its precise target site using patch-clamp techniques and receptor binding assays in guinea-pig ventricular myocytes. Exposure of myocytes to a glucose-free perfusate containi...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-200003000-00014
更新日期:2000-03-01 00:00:00
abstract::The positive inotropic action of phenylephrine in cardiac muscle is mediated by alpha- and beta-adrenoceptors. Data suggest the responsiveness of myocardium to inotropic agents is altered in cardiac disease. We evaluated the actions of phenylephrine on isometric contraction and K+-induced contracture in isolated cat r...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198403000-00005
更新日期:1984-03-01 00:00:00
abstract::To investigate the antianginal action of nitroglycerin and nifedipine, systemic and right heart pressures, cardiac output, oxygen consumption, and radionuclide left ventricular ejection fraction and volume were measured in 14 men with stable effort angina and a positive exercise electrocardiogram. Exercise tests were ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-198903000-00002
更新日期:1989-03-01 00:00:00
abstract::Both population (mass) strategies and targeted strategies for the management of high blood pressure are necessary. However, it has yet to be proven that reducing blood pressure by lifestyle changes in the population will confer the same cardiovascular benefit that results from lowering blood pressure by drugs. It is i...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
doi:10.1097/00005344-199627003-00008
更新日期:1996-01-01 00:00:00
abstract::NSP-513, a novel potent and selective phosphodiesterase 3 (PDE 3) inhibitor, and cilostazol, a previously developed PDE 3 inhibitor, were compared with respect to antiplatelet, antithrombotic, and hemodynamic effects. In the in vitro antiplatelet aggregation studies, NSP-513 and cilostazol inhibited collagen-induced c...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-200004000-00012
更新日期:2000-04-01 00:00:00
abstract::We examined the effects of NIP-121, a potassium channel opener, on KCl- and norepinephrine (NE)-induced contraction, the phasic-contraction under the Ca(2+)-free condition and cytosolic free-Ca2+ mobilization using isolated rat aorta. NIP-121 as well as cromakalim inhibited, in the KCl- and NE-contractions concentrati...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:1994-12-01 00:00:00
abstract::To study the role of intrinsic sympathomimetic activity (ISA) in beta-blocker-induced changes of beta-adrenoceptors, the effects of administration of several beta-blockers for 9 days on lymphocyte beta 2-adrenoceptor density--assessed by 125iodocyanopindolol binding--were investigated in 47 normotensive volunteers. Pr...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:
更新日期:1986-01-01 00:00:00