Antenatal Use of Ambroxol for the Prevention of Infant Respiratory Distress Syndrome

Laoag-Fernandez, Jovelle B.; Fernandez, Alex; Maruo, Takeshi

doi:10.1111/j.1447-0756.2000.tb01327.x

Cited by 24 publications

(20 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although gene therapy [78] is theoretically promising, there is no ethical justification to experiment on patients who have alternative, safe and effective treatment. However, stem cell therapy with a low-risk conditioning regimen [79] may have a role in GD and other metabolic disorders but, again, there is the challenge of affecting neurological features [80].…”

Section: Therapeutics Of Gdmentioning

confidence: 99%

Gaucher Disease: Clinical, Biological and Therapeutic Aspects

Dandana¹,

Khelifa²,

Chahed³

et al. 2015

Pathobiology

112

View full text Add to dashboard Cite

We present a brief review of Gaucher disease (GD), the most common lysosomal storage disease. GD is a rare autosomal recessive disorder characterized by the defective function of the catabolic enzyme β-glucocerebrosidase (GBA), leading to an accumulation of its substrate, glucocerebroside. Clinical signs and symptoms include neurological dysfunctions, bone infarcts and malformations, hepatosplenomegaly and hypersplenism leading to anemia, neutropenia and thrombocytopenia. Enzyme replacement therapy with recombinant GBA is the mainstay of treatment for GD, which became the first successfully managed lipid storage disease. Future treatments may include oral enzyme replacement and/or gene therapy interventions.

show abstract

Section: Therapeutics Of Gdmentioning

confidence: 99%

Gaucher Disease: Clinical, Biological and Therapeutic Aspects

Dandana¹,

Khelifa²,

Chahed³

et al. 2015

Pathobiology

112

View full text Add to dashboard Cite

show abstract

“…Ambroxol has also been used for treatment or prophylaxis or both of neonatal respiratory distress syndrome. 95 We have administered Ambroxol off-label to 12 mildly affected patients with type I GD in 2009 with only the 2 thinnest patients having positive results, suggesting the need for higher doses. Hence, formal clinical trials, using higher doses, are necessary before ambroxol can be considered for its potential to benefit type III GD.…”

mentioning

confidence: 99%

How I treat Gaucher disease

Zimran

2011

Blood

145

135

View full text Add to dashboard Cite

This review presents a cohesive approach to treating patients with Gaucher disease. The spectrum of the clinical presentation of the disease is broad, yet heretofore there was only one diseasespecific treatment. In the past 2 years, a global shortage of this product has resulted in reassessment of the "one enzyme-one disease-one therapy" mantra. It has also showcased the multiple levels that engage the patient, the treating physician, and the third-party insurer in providing adequate treatment to all symptomatic patients. The key points summarizing the way I manage my patients include accurate enzymatic diagnosis with mutation analysis (for some prognostication and better carrier detection in the family), a detailed follow-up every 6-12 months (with an option to see consultants and attention to comorbidities), and initiation of enzyme replacement therapy according to symptoms or deterioration in clinically significant features or both. I do not treat patients with very mild disease, but I consider presymptomatic therapy for patients at risk, including young women with poor obstetric history. I prefer the minimal-effective dose rather than the maximally tolerated dose, and when the difference between high-dose and lower-dose regimens is (merely statistically significant but) clinically meaningless, minimizing the burden on society by advocating less-expensive treatments is ethically justified. (Blood. 2011;118(6): 1463-1471) IntroductionThe purpose of this review is to present a cohesive approach to treating patients with Gaucher disease (GD). As can be appreciated, the spectrum of the clinical presentation of the disease is broad, yet heretofore there was only one disease-specific treatment. In the past 2 years, a global shortage of this product has resulted in reassessment of the "one enzyme-one disease-one therapy" mantra. It has also showcased the multiple levels that engage the patient, the treating physician, and the third-party insurer, in providing adequate treatment for all symptomatic patients with GD. As a treating physician dedicated to GD even before the era of enzyme replacement therapy (ERT), my mandate and inspiration has always been to provide the best therapy with the least malfeasance. Description of GDGD is one of the most common glycolipid storage disorders, caused by an inherited deficiency of the lysosomal enzyme ␤-glucocerebrosidase, leading to accumulation of the substrate glucocerebroside in the cells of the macrophage-monocyte system. 1 Accordingly, key disease features are related to splenomegaly with hypersplenism, hepatomegaly, and bone involvement. Although a single-gene disorder, phenotypic expression is extremely variable, ranging from totally asymptomatic (only detectable by DNA analysis or enzyme deficiency) to a lethal newborn form with hydrops fetalis and ichthyosis. Many manifestations, some notuncommon and others very rare, cannot be explained by storage per se; examples include immunologic abnormalities, increased prevalence of certain malignancies with relative paucity of ...

show abstract

“…It is an effective expectorant, has been shown to normalize the structure of surfactant, to prevent the infant respiratory distress syndrome, and to be effective for the treatment of bronchitis (Renovanz, 1975;Laoag-Fernandez et al, 2000;Matthys et al, 2000). Interestingly, it has been reported that ambroxol has pharmacological effects that cannot be explained by its already described properties on airway epithelia: this compound has been shown to suppress the cough reflex.…”

mentioning

confidence: 99%

Inhibition of Tetrodotoxin (TTX)-Resistant and TTX-Sensitive Neuronal Na⁺ Channels by the Secretolytic Ambroxol

Weiser

Wilson²

2002

Mol Pharmacol

View full text Add to dashboard Cite

Ambroxol has a long history for the treatment of airway diseases because of its beneficial effects on surfactant synthesis and mucus-modifying properties. Some findings, however, point to an additional effect on neuronal signal transduction: ambroxol can suppress reflexes such as the cough or the corneal reflex. The airways and the cornea are innervated by C-fibers, which express voltage-gated Na ϩ channels with and without sensitivity to tetrodotoxin (TTX). In this study, we performed voltage-clamp experiments to investigate whether ambroxol affects these channel types. In rat dorsal root ganglia, TTX-resistant Na ϩ currents were suppressed in a concentration-dependent manner with IC 50 values of 35.2 and 22.5 M for tonic and phasic block, respectively. Depolarizing prepulses increased the potency of ambroxol, and steady-state inhibition curves were shifted to more negative values. The inhibition was not frequency-dependent. TTX-sensitive currents were inhibited with lower potency (ϳ50% inhibition with 100 M). Recombinant rat brain IIA channels in Chinese hamster ovary cells were blocked with IC 50 values of 111.5 and 57.6 M for tonic and phasic block, respectively; in contrast to TTX-resistant channels the block was frequency-dependent. Thus, ambroxol indeed blocks neuronal voltage-gated Na ϩ channels, and TTXresistant channels in sensory neurons were more sensitive than TTX-sensitive. Compared with known local anesthetics (e.g., lidocaine or benzocaine), the potency for Na ϩ channel block was relatively high. A recent clinical trial has further confirmed that ambroxol relieved pain and was beneficial in patients who suffered from sore throat.

show abstract

Antenatal Use of Ambroxol for the Prevention of Infant Respiratory Distress Syndrome

Abstract: Antenatal administration of ambroxol resulted in a significant decrease in the incidence of IRDS as well as perinatal morbidity and mortality. Due to the efficacy and safety of this drug, it might be useful for the prevention of IRDS.

Cited by 24 publications

References 13 publications

Gaucher Disease: Clinical, Biological and Therapeutic Aspects

Gaucher Disease: Clinical, Biological and Therapeutic Aspects

How I treat Gaucher disease

Inhibition of Tetrodotoxin (TTX)-Resistant and TTX-Sensitive Neuronal Na⁺ Channels by the Secretolytic Ambroxol

Contact Info

Product

Resources

About

Antenatal Use of Ambroxol for the Prevention of Infant Respiratory Distress Syndrome

Abstract: Antenatal administration of ambroxol resulted in a significant decrease in the incidence of IRDS as well as perinatal morbidity and mortality. Due to the efficacy and safety of this drug, it might be useful for the prevention of IRDS.

Cited by 24 publications

References 13 publications

Gaucher Disease: Clinical, Biological and Therapeutic Aspects

Gaucher Disease: Clinical, Biological and Therapeutic Aspects

How I treat Gaucher disease

Inhibition of Tetrodotoxin (TTX)-Resistant and TTX-Sensitive Neuronal Na+ Channels by the Secretolytic Ambroxol

Contact Info

Product

Resources

About

Inhibition of Tetrodotoxin (TTX)-Resistant and TTX-Sensitive Neuronal Na⁺ Channels by the Secretolytic Ambroxol