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Indian Pediatrics May 1990
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Expert Opinion on Drug Metabolism &... Mar 2019Major unmet needs remain for improved antibiotic treatment in lung infections. While development of new antibiotics is needed to overcome resistance, other approaches to... (Review)
Review
Major unmet needs remain for improved antibiotic treatment in lung infections. While development of new antibiotics is needed to overcome resistance, other approaches to optimize therapy using existing agents are also attractive. Ambroxol induces lung autophagy at human-relevant doses and improves lung levels of several approved antibiotics. Areas covered: This review discusses preclinical and clinical studies of the effects of ambroxol (and its prodrug precursor bromhexine) co-treatment upon levels of antibiotics in lung tissue, sputum, and bronchoalveolar lavage fluid. Expert opinion: Ambroxol co-treatment is associated with significant increases in lung tissue and airway surface fluid levels of a range of antibiotics including beta lactams, glycopeptides, macrolides, nitrofurans, and rifamycins. In most cases, the increased levels are only modest and are insufficient to overcome high-level resistance against that same antibiotic class, and so co-treatment with ambroxol is unlikely to alter clinical outcomes. Additionally, for most antibiotics there is no evidence that outcomes in non-resistant disease are improved by higher drug levels, and there is limited efficacy of co-treatment of antibiotics with ambroxol for most pathogens. The two cases where ambroxol may improve therapy are rifampin-sensitive tuberculosis and non-tuberculous mycobacterial infection, and vancomycin sensitive methicillin resistant Staphylococcus aureus pneumonia.
Topics: Ambroxol; Animals; Anti-Bacterial Agents; Bacterial Infections; Bromhexine; Drug Resistance, Bacterial; Expectorants; Humans; Lung; Lung Diseases; Tissue Distribution
PubMed: 30721101
DOI: 10.1080/17425255.2019.1578748 -
Archives of Physiology and Biochemistry Dec 2022Lipase hydrolyses the ester bonds in triglyceride. It is an important enzyme in medicine and industry. Some pathogen bacteria use this exoenzyme to disrupt the...
Lipase hydrolyses the ester bonds in triglyceride. It is an important enzyme in medicine and industry. Some pathogen bacteria use this exoenzyme to disrupt the extracellular matrix of host organisms. uses various extracellular enzymes such as lipase to invade its host. In this report, for the first time, bromhexine was introduced as an inhibitor of lipase. Bromhexine is a mucolytic drug which is used in the treatment of respiratory tract disorders. The results showed that bromhexine inhibited the enzyme by competitive inhibition. IC and values of the drug were 0.049 mM and 0.02 mM, respectively. Arrhenius plot showed that the drug reduced the activation energy. The enzyme was purified and SDS-PAGE showed that its molecular weight is 13 kDa. Fluorescence measurement revealed that binding of the drug to lipase could make structural changes in the enzyme. Inhibition of lipase by bromhexine could be applicable in medicine.
Topics: Lipase; Kinetics; Bromhexine; Expectorants; Triglycerides; Esters
PubMed: 32633559
DOI: 10.1080/13813455.2020.1788606 -
Internal and Emergency Medicine Aug 2020Of huge importance now is to provide a fast, cost-effective, safe, and immediately available pharmaceutical solution to curb the rapid global spread of SARS-CoV-2.... (Review)
Review
Of huge importance now is to provide a fast, cost-effective, safe, and immediately available pharmaceutical solution to curb the rapid global spread of SARS-CoV-2. Recent publications on SARS-CoV-2 have brought attention to the possible benefit of chloroquine in the treatment of patients infected by SARS-CoV-2. Whether chloroquine can treat SARS-CoV-2 alone and also work as a prophylactic is doubtful. An effective prophylactic medication to prevent viral entry has to contain, at least, either a protease inhibitor or a competitive virus ACE2-binding inhibitor. Using bromhexine at a dosage that selectively inhibits TMPRSS2 and, in so doing, inhibits TMPRSS2-specific viral entry is likely to be effective against SARS-CoV-2. We propose the use of bromhexine as a prophylactic and treatment. We encourage the scientific community to assess bromhexine clinically as a prophylactic and curative treatment. If proven to be effective, this would allow a rapid, accessible, and cost-effective application worldwide.
Topics: Betacoronavirus; Bromhexine; COVID-19; Coronavirus Infections; Expectorants; Humans; Pandemics; Pneumonia, Viral; SARS-CoV-2; Serine Endopeptidases; Virus Internalization
PubMed: 32458206
DOI: 10.1007/s11739-020-02383-3 -
Journal of Investigative Medicine : the... Oct 2023Bromhexine is a potent inhibitor of transmembrane serine protease 2 and appears to have an antiviral effect in controlling influenza and parainfluenza infection;... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Bromhexine is a potent inhibitor of transmembrane serine protease 2 and appears to have an antiviral effect in controlling influenza and parainfluenza infection; however, its efficacy in COVID-19 is controversial.
METHODS
A group of hospitalized patients with confirmed COVID-19 pneumonia were randomized using 1:1 allocation to either standard treatment lopinavir/ritonavir and interferon beta-1a or bromhexine 8 mg four times a day in addition to standard therapy. The primary outcome was clinical improvement within 28 days, and the secondary outcome measures were time to hospital discharge, all-cause mortality, duration of mechanical ventilation, the temporal trend in 2019-nCoV reverse transcription-polymerase chain reaction positivity and the frequency of adverse drug events within 28 days from the start of medication.
RESULTS
A total of 111 patients were enrolled in this randomized clinical trial and data from 100 patients (48 patients in the treatment arm and 52 patients in the control arm) were analyzed. There was no significant difference in the primary outcome of this study, which was clinical improvement. There was no significant difference in the average time to hospital discharge between the two arms. There were also no differences observed in the mean intensive care unit stay, frequency of intermittent mandatory ventilation, duration of supplemental oxygenation or risk of death by day 28 noted between the two arms.
CONCLUSION
Bromhexine is not an effective treatment for hospitalized patients with COVID-19. The potential prevention benefits of bromhexine in asymptomatic postexposure or with mild infection managed in the community remain to be determined.
Topics: Humans; COVID-19; SARS-CoV-2; Bromhexine; Treatment Outcome; Patient Discharge
PubMed: 33722999
DOI: 10.1136/jim-2020-001747 -
Voprosy Virusologii May 2022COVID-19 (novel coronavirus disease 2019), caused by the SARS-CoV-2 virus, has various clinical manifestations and several pathogenic pathways. Although several...
COVID-19 (novel coronavirus disease 2019), caused by the SARS-CoV-2 virus, has various clinical manifestations and several pathogenic pathways. Although several therapeutic options have been used to control COVID-19, none of these medications have been proven to be a definitive cure. Transmembrane serine protease 2 (TMPRSS2) is a protease that has a key role in the entry of SARS-CoV-2 into host cells. Following the binding of the viral spike (S) protein to the angiotensin-converting enzyme 2 (ACE2) receptors of the host cells, TMPRSS2 processes and activates the S protein on the epithelial cells. As a result, the membranes of the virus and host cell fuse. Bromhexine is a specific TMPRSS2 inhibitor that potentially inhibits the infectivity cycle of SARS-CoV-2. Moreover, several clinical trials are evaluating the efficacy of bromhexine in COVID-19 patients. The findings of these studies have shown that bromhexine is effective in improving the clinical outcomes of COVID-19 and has prophylactic effects by inhibiting TMPRSS2 and viral penetration into the host cells. Bromhexine alone cannot cure all of the symptoms of SARS-CoV-2 infection. However, it could be an effective addition to control and prevent the disease progression along with other drugs that are used to treat COVID-19. Further studies are required to investigate the efficacy of bromhexine in COVID-19.
Topics: Bromhexine; Humans; SARS-CoV-2; Spike Glycoprotein, Coronavirus; Virus Internalization; COVID-19 Drug Treatment
PubMed: 35521985
DOI: 10.36233/0507-4088-106 -
FEBS Letters Jan 2020Bromhexine was reported to relieve the symptoms of Sjogren Syndrome at an early stage. However, the underlying mechanism remains unclear. Here, we administered...
Bromhexine was reported to relieve the symptoms of Sjogren Syndrome at an early stage. However, the underlying mechanism remains unclear. Here, we administered bromhexine at low doses in human primary conjunctival fornix epithelial cells, and found it stimulated MUC5AC secretion and lipid droplet production. Expression of the metabolism-related gene CHML was also upregulated by bromhexine treatment, and REP2, the protein produced by the CHML gene, was induced. These results suggest that bromhexine is a potential candidate eye drop drug for the treatment of multiple types of dry eye disease, not only limited to the treatment of dry eyes in Sjogren Syndrome.
Topics: Adaptor Proteins, Signal Transducing; Bromhexine; Cells, Cultured; Conjunctiva; Epithelial Cells; Expectorants; Humans; Lipid Droplets; Mucin 5AC
PubMed: 31365127
DOI: 10.1002/1873-3468.13560 -
Prescrire International Apr 2015
Topics: Adolescent; Age Factors; Ambroxol; Anaphylaxis; Bromhexine; Child; Child, Preschool; Expectorants; Humans; Patient Safety; Risk Assessment; Risk Factors
PubMed: 25941704
DOI: No ID Found -
Ugeskrift For Laeger Jul 1974
Review
Topics: Adult; Aged; Animals; Bromhexine; Bronchitis; Cats; Chronic Disease; Depression, Chemical; Humans; Middle Aged; Rabbits; Rats; Sputum
PubMed: 4605541
DOI: No ID Found -
Clinical and Translational Science Nov 2020This open-label randomized controlled pilot study aimed to test the study feasibility of bromhexine hydrochloride (BRH) tablets for the treatment of mild or moderate... (Randomized Controlled Trial)
Randomized Controlled Trial
This open-label randomized controlled pilot study aimed to test the study feasibility of bromhexine hydrochloride (BRH) tablets for the treatment of mild or moderate coronavirus disease 2019 (COVID-19) and to explore its clinical efficacy and safety. Patients with mild or moderate COVID-19 were randomly divided into the BRH group or the control group at a 2:1 ratio. Routine treatment according to China's Novel Coronavirus Pneumonia Diagnosis and Treatment Plan was performed in both groups, whereas patients in the BRH group were additionally given oral BRH (32 mg t.i.d.) for 14 consecutive days. The efficacy and safety of BRH were evaluated. A total of 18 patients with moderate COVID-19 were randomized into the BRH group (n = 12) or the control group (n = 6). There were suggestions of BRH advantage over placebo in improved chest computed tomography, need for oxygen therapy, and discharge rate within 20 days. However, none of these findings were statistically significant. BRH tablets may potentially have a beneficial effect in patients with COVID-19, especially for those with lung or hepatic injury. A further definitive large-scale clinical trial is feasible and necessary.
Topics: Adult; Bromhexine; Female; Follow-Up Studies; Humans; Male; Middle Aged; Pilot Projects; SARS-CoV-2; Tablets; COVID-19 Drug Treatment
PubMed: 32881359
DOI: 10.1111/cts.12881