Phosphodiesterase inhibitors: Potential role in the respiratory distress of neonates

Mokrá, Daniela; Mokrý, Juraj; Matasová, Katarína

doi:10.1002/ppul.24082

Cited by 7 publications

(9 citation statements)

References 77 publications

(110 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…PDEs include different species subtypes with different affinities and specificities for different substrates. It has been shown [ 28 ] that the use of PDE inhibitors in addition to inhaled prostacyclin prolongs the duration of action of prostacyclin, improves haemodynamics, and does not affect systemic arterial blood pressure or gas exchange, but the long-term efficacy of PAH treatment with PDE inhibitors alone has not been demonstrated.…”

Section: Current Status Of Pah Treatment With Inhaled Formulationsmentioning

confidence: 99%

Advances in the Study of Inhaled Formulations for the Treatment of Pulmonary Arterial Hypertension

Han

Chen

et al. 2022

Applied Bionics and Biomechanics

View full text Add to dashboard Cite

Pulmonary arterial hypertension (PAH) is a serious disease with reduced systemic circulation and low bioavailability associated with conventional and dosed therapy, which inhaled drugs can avoid. A mean pulmonary artery pressure (mPAP) of ≥25 mmHg ( 1 mmHg = 0.133 kPa ) at rest or ≥30 mmHg during exercise and a pulmonary capillary pressure or left atrial pressure (PLA) of ≤15 mmHg can be diagnosed with PAH. Pulmonary hypertension is classified into primary PAH and secondary PAH according to the presence or absence of principles or risk factors. The main symptoms of pulmonary hypertension include dyspnoea, syncope, weakness, chest pain, and the presence of varying degrees of peripheral oedema. It is a highly pathogenic and life-threatening disease and can lead to delays in treatment if not diagnosed in time. In the past few years, the studies related to this progressed slowly, which brought great harm to patients with PAH. Reports showed that patients diagnosed with PAH should receive routine preventative care, such as pneumococcal and influenza vaccinations. Inhalation therapy is mainly used for the treatment of respiratory diseases and is of great interest due to the concentration of the drug in the airways and lung tissues. Therefore, the present situation of pulmonary hypertension and the characteristics of inhalation preparation were reviewed in this paper to provide some related cue for the treatment of pulmonary hypertension. In the future, it is necessary to develop more treatment methods for pulmonary hypertension.

show abstract

Section: Current Status Of Pah Treatment With Inhaled Formulationsmentioning

confidence: 99%

Advances in the Study of Inhaled Formulations for the Treatment of Pulmonary Arterial Hypertension

Han

Chen

et al. 2022

Applied Bionics and Biomechanics

View full text Add to dashboard Cite

show abstract

“…5 Potential candidates for targeting neonatal lung inflammation are phosphodiesterase (PDE) inhibitors, such as methylxanthines and their derivates. 8 Caffeine, a methylxanthine widely used in the treatment of apnea in preterm infants, has been shown to decrease the incidence of BPD. 9 Although the mechanism is still discussed, caffeine's property as a weak, non-specific PDE inhibitor might contribute to its beneficial effect on BPD.…”

Section: Introductionmentioning

confidence: 99%

Detrimental Effects of an Inhaled Phosphodiesterase-4 Inhibitor on Lung Inflammation in Ventilated Preterm Lambs Exposed to Chorioamnionitis Are Dose Dependent

Hütten

Fehrholz

Konrad

et al. 2019

Journal of Aerosol Medicine and Pulmonary Drug Delivery

View full text Add to dashboard Cite

Background: Treatment of bronchopulmonary dysplasia (BPD) in preterm infants is challenging due to its multifactorial origin. In rodent models of neonatal lung injury, selective inhibition of PDE4 has been shown to exert anti-inflammatory properties in the lung. We hypothesized that GSK256066, a highly selective, inhalable PDE4 inhibitor, would have beneficial effects on lung injury and inflammation in a triple hit lamb model of Ureaplasma parvum (UP)-induced chorioamnionitis, prematurity and mechanical ventilation. Methods: 21 preterm lambs were surgically delivered preterm at 129d after 7d intrauterine exposure to UP. 16 animals were subsequently ventilated for 24 hours and received endotracheal surfactant and intravenous caffeine citrate. 10 animals were randomized to receive twice a high (10 µg/kg) or low dose (1 µg/kg) of nebulized PDE4 inhibitor. Results: Nebulization of high, but not low doses of PDE4 inhibitor led to a significant decrease in pulmonary PDE activity, and was associated with lung injury and vasculitis, influx of neutrophils and increased pro-inflammatory cytokine mRNA levels. Conclusions: Contrary to our hypothesis, we found in our model a dose-dependent proinflammatory effect of an inhaled highly selective PDE4 inhibitor in the lung. Our findings indicate the narrow therapeutic range of inhaled PDE4 inhibitors in the preterm population.

show abstract

“…Such a variety of physiological involvement inevitably suggests involvement in human pathology as well. Indeed, numerous reviews have showed evidence on PDE-mediated implications in such diseases, as cancer ( Peng et al, 2018 ), neurologic ( Halene and Siegel, 2007 ; Nthenge-Ngumbau and Mohanakumar, 2018 ; Gurney, 2019 ), inflammatory ( Page and Spina, 2011 ), pulmonary ( Fan Chung, 2006 ; Mokry et al, 2018 ; Joskova et al, 2020 ; Kawamatawong, 2021 ; Mokra and Mokry, 2021 ), pediatric ( Mokra et al, 2018 ), and cardiovascular disorders ( Ravipati et al, 2007 ), among others. Additionally, the PDE enzymes are characterized by several factors, including a high degree of isoform variation, a high degree of isoform specificity towards substrates, distinct tissue expression and subcellular localization patterns among different isoforms, and the generally favorable intracellular cyclic nucleotides’ concentration, that further highlight their potential as drug targets ( Bender and Beavo, 2006 ).…”

Section: The Cyclic Nucleotide Phosphodiesterase Superfamily—overviewmentioning

confidence: 99%

Recent developments of phosphodiesterase inhibitors: Clinical trials, emerging indications and novel molecules

et al. 2022

View full text Add to dashboard Cite

The phosphodiesterase (PDE) enzymes, key regulator of the cyclic nucleotide signal transduction system, are long-established as attractive therapeutic targets. During investigation of trends within clinical trials, we have identified a particularly high number of clinical trials involving PDE inhibitors, prompting us to further evaluate the current status of this class of therapeutic agents. In total, we have identified 87 agents with PDE-inhibiting capacity, of which 85 interact with PDE enzymes as primary target. We provide an overview of the clinical drug development with focus on the current clinical uses, novel molecules and indications, highlighting relevant clinical studies. We found that the bulk of current clinical uses for this class of therapeutic agents are chronic obstructive pulmonary disease (COPD), vascular and cardiovascular disorders and inflammatory skin conditions. In COPD, particularly, PDE inhibitors are characterised by the compliance-limiting adverse reactions. We discuss efforts directed to appropriately adjusting the dose regimens and conducting structure-activity relationship studies to determine the effect of structural features on safety profile. The ongoing development predominantly concentrates on central nervous system diseases, such as schizophrenia, Alzheimer’s disease, Parkinson’s disease and fragile X syndrome; notable advancements are being also made in mycobacterial infections, HIV and Duchenne muscular dystrophy. Our analysis predicts the diversification of PDE inhibitors’ will continue to grow thanks to the molecules in preclinical development and the ongoing research involving drugs in clinical development.

show abstract

Phosphodiesterase inhibitors: Potential role in the respiratory distress of neonates

Cited by 7 publications

References 77 publications

Advances in the Study of Inhaled Formulations for the Treatment of Pulmonary Arterial Hypertension

Advances in the Study of Inhaled Formulations for the Treatment of Pulmonary Arterial Hypertension

Detrimental Effects of an Inhaled Phosphodiesterase-4 Inhibitor on Lung Inflammation in Ventilated Preterm Lambs Exposed to Chorioamnionitis Are Dose Dependent

Recent developments of phosphodiesterase inhibitors: Clinical trials, emerging indications and novel molecules

Contact Info

Product

Resources

About