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Drugs Jul 2010The acute respiratory distress syndrome (ARDS) arises from direct and indirect injury to the lungs and results in a life-threatening form of respiratory failure in a... (Review)
Review
The acute respiratory distress syndrome (ARDS) arises from direct and indirect injury to the lungs and results in a life-threatening form of respiratory failure in a heterogeneous, critically ill patient population. Critical care technologies used to support patients with ARDS, including strategies for mechanical ventilation, have resulted in improved outcomes in the last decade. However, there is still a need for effective pharmacotherapies to treat ARDS, as mortality rates remain high. To date, no single pharmacotherapy has proven effective in decreasing mortality in adult patients with ARDS, although exogenous surfactant replacement has been shown to reduce mortality in the paediatric population with ARDS from direct causes. Several promising therapies are currently being investigated in preclinical and clinical trials for treatment of ARDS in its acute and subacute, exudative phases. These include exogenous surfactant therapy, beta(2)-adrenergic receptor agonists, antioxidants, immunomodulating agents and HMG-CoA reductase inhibitors (statins). Recent research has also focused on prevention of acute lung injury and acute respiratory distress in patients at risk. Drugs such as captopril, rosiglitazone and incyclinide (COL-3), a tetracycline derivative, have shown promising results in animal models, but have not yet been tested clinically. Further research is needed to discover therapies to treat ARDS in its late, fibroproliferative phase. Given the vast number of negative clinical trials to date, it is unlikely that a single pharmacotherapy will effectively treat all patients with ARDS from differing causes. Future randomized controlled trials should target specific, more homogeneous subgroups of patients for single or combination therapy.
Topics: Adrenergic Agonists; Adult; Antioxidants; Clinical Trials as Topic; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Immunologic Factors; Models, Biological; Respiration, Artificial; Respiratory Distress Syndrome; Salvage Therapy; Surface-Active Agents
PubMed: 20568833
DOI: 10.2165/10898570-000000000-00000 -
Expert Opinion on Investigational Drugs May 2022Drug repurposing can be a successful approach to deal with the scarcity of cost-effective therapies in situations such as the COVID-19 pandemic. Tetracyclines have...
INTRODUCTION
Drug repurposing can be a successful approach to deal with the scarcity of cost-effective therapies in situations such as the COVID-19 pandemic. Tetracyclines have previously shown efficacy in preclinical acute respiratory distress syndrome (ARDS) models and initial predictions and experimental reports suggest a direct antiviral activity against SARS-CoV2. Furthermore, a few clinical reports indicate their potential in COVID-19 patients. In addition to the scarcity and limitations of the scientific evidence, the effectiveness of tetracyclines in experimental ARDS has been proven extensively, counteracting the overt inflammatory reaction and fibrosis sequelae due to a synergic combination of pharmacological activities.
AREAS COVERED
This paper discusses the scientific evidence behind the application of tetracyclines for ARDS/COVID-19.
EXPERT OPINION
The benefits of their multi-target pharmacology and their safety profile overcome the limitations, such as antibiotic activity and low commercial interest. Immunomodulatory tetracyclines and novel chemically modified non-antibiotic tetracyclines have therapeutic potential. Further drug repurposing studies in ARDS and severe COVID-19 are necessary.
Topics: Anti-Bacterial Agents; Drug Repositioning; Humans; Pandemics; RNA, Viral; Respiratory Distress Syndrome; SARS-CoV-2; Tetracyclines; COVID-19 Drug Treatment
PubMed: 35294307
DOI: 10.1080/13543784.2022.2054325