Aminophylline for treating asthma and chronic obstructive pulmonary disease

Nuhoğlu, Yonca; Nuhoğlu, Çağatay

doi:10.1586/17476348.2.3.305

Cited by 15 publications

(11 citation statements)

References 64 publications

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“…We evaluated aminophylline (AMO, theophylline ethylenediamine) as a nonselective adenosine receptor antagonist because it is available for clinical use (10, 11). We also evaluated the nonclinical compound ATL801 (N-(5-(1-cyclopropyl-2,6-dioxo-3-propyl-2,3,6,7-tetrahydro-1H-purin-8-yl)pyridin-2-yl)-N-ethyl-6-nicotinamide), because it is a selective and bioavailable A 2B AR antagonist.…”

Section: Introductionmentioning

confidence: 99%

Adenosine A2B Receptor Blockade Slows Growth of Bladder and Breast Tumors

Cekic

Sağ

et al. 2012

The Journal of Immunology

188

173

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The accumulation of high levels of adenosine in tumors activates A2A and A2B receptors on immune cells and inhibits their ability to suppress tumor growth. Deletion of A2AARs has been reported to activate anti-tumor T cells, stimulates DC function and inhibits angiogenesis. Here we evaluated the effects of intermittent intratumor injection of a non-selective adenosine receptor antagonist, aminophylline (AMO, theophylline ethylenediamine) and, for the first time, a selective A2BAR antagonist, ATL801. AMO and ATL801 slowed the growth of MB49 bladder and 4T1 breast tumors in syngeneic mice, and reduced by 85% metastasizes of breast cancer cells from mammary fat to lung. Based on experiments with A2AAR−/− or A2BAR−/− mice, the effect of AMO injection was unexpectedly attributed to A2BAR and not to A2AAR blockade. AMO and ATL801 significantly increased tumor levels of IFNγ and the interferon-inducible chemokine CXCL10, which is a ligand for CXCR3. This was associated with an increase in activated tumor-infiltrating CXCR3+ T cells and a decrease in endothelial cell precursors within tumors. Tumor growth inhibition by AMO or ATL801 was eliminated in CXCR3−/− mice and in RAG1−/− mice that lack mature T cells. In RAG1−/− mice A2BAR deletion enhanced CD86 expression on CD11b- DCs. Bone marrow chimera experiments demonstrated that CXCR3 and A2BAR expression on bone marrow cells are required for the anti-tumor effects of AMO. The data suggest that blockade of A2BARs enhances DC activation and CXCR3-dependent anti-tumor responses.

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Section: Introductionmentioning

confidence: 99%

Adenosine A2B Receptor Blockade Slows Growth of Bladder and Breast Tumors

Cekic

Sağ

et al. 2012

The Journal of Immunology

188

173

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“…Penggunaan aminofilin/teofilin untuk terapi asma di luar negeri sudah jarang ditemui karena gejala toksisitas yang sering muncul, 9 serta efikasinya menurun bila dibandingkan dengan Inhaled Corticosteroids (ICSs) dan inhalasi beta-2 agonis aksi panjang. 5 Bukti mengenai kejadian ADR dari teofilin dan juga aminofilin telah banyak ditemukan, [10][11][12][13][14] sehingga penggunaannya di luar negeri sudah ditinggalkan. Menurut pedoman pengobatan asma Global Initiative for Asthma (GINA) 2016, efikasi dan keamanan dari penggunaan aminofilin termasuk dalam kategori kurang serta lebih berisiko untuk menimbulkan efek samping.…”

Section: 6-8unclassified

Effectiveness and Toxicity Risk of Intravenous Aminophylline in Exacerbation Asthma Treatment

Lorensia

Ikawati

Andayani

et al. 2018

Indones J Clin Pharm

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4Program Studi Apoteker, Fakultas Farmasi Universitas Surabaya, Surabaya AbstrakAsma merupakan penyakit inflamasi kronis pada saluran pernafasan yang mempunyai prevalensi global yang cukup besar. Perburukan penyakit asma berupa serangan asma yang menyebabkan peningkatan gejala asma dan penurunan fungsi paru secara progresif. Salah satu obat asma yang masih sering digunakan di Indonesia adalah aminofilin intravena. Aminofilin merupakan obat dengan rentang terapi sempit yang berisiko menyebabkan toksisitas obat, namun data perbandingan keuntungan efektivitas dan keamanan obat tersebut belum memadai. Penelitian ini bertujuan untuk mengetahui efektivitas aminofilin intravena pada pengobatan awal serangan asma berupa perbaikan gejala asma dan kejadian toksisitas terkait gejala yang muncul dan kadar teofilin dalam darah di suatu rumah sakit di Surabaya, Indonesia. Penelitian ini menggunakan metode pra-eksperimental yang dilaksanakan sejak 2014 hingga 2016. Sebanyak 27 pasien terlibat dalam penelitian ini. Terapi yang diberikan adalah aminofilin intravena selama satu jam. Metode sampling yang digunakan adalah consecutive sampling dengan teknik analisis deskriptif dan jum. Semua subjek penelitian menunjukkan perbaikan gejala serangan asma dengan terapi aminofilin intravena selama satu jam, dan tidak ada yang mengalami toksisitas karena kadar teofilin dalam darah di bawah rentang terapi. Aminofilin masih efektif dalam mengurangi gejala pada serangan asma dan tidak menunjukkan risiko toksisitas.Kata kunci: Aminofilin, efektivitas, serangan asma, toksisitas Effectiveness and Toxicity Risk of Intravenous Aminophylline in Exacerbation Asthma Treatment AbstractAsthma is a chronic inflammatory disease in the respiratory tract that has a considerable global prevalence. The worsening of asthma is an asthma attack that causes asthma symptoms to increase and decreased lung function progressively. One of the most commonly used asthma medications in Indonesia is intravenous aminophylline. Aminophylline is a drug with a narrow range of therapies that is at risk of causing drug toxicity, but the comparative data on the efficacy and safety benefits of the drug are inadequate. This study aimed to determine the effectiveness of aminophylline intravenously in the early treatment of asthma attacks in the form of improvements in asthma symptoms and toxicity events related to the symptoms that appear and blood theophylline levels in a hospital in Surabaya, Indonesia. This study used a pre-experimental method which was carried out from 2014 to 2016. A total of twenty seven patients were involved in the study. The therapy given was aminophylline intravenously for one hour. The sampling method used was consecutive sampling with descriptive analysis technique. All subjects showed improved symptoms of asthma attacks with intravenous aminophylline therapy for one hour, and none had toxicity due to theophylline levels in the blood below the therapeutic range. Aminophylline is still effective in reducing symptoms in asthma attacks and does not indic...

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“…), whereas others have been used as therapeutic agents, and recently have been marked differentiative properties on tumor cells. 25 , 26 The best known of these natural alkaloids are theophylline (TH, 1,3-dimethylxanthine), theobromine (3,7-dimethylxanthine), aminophylline (1,3-dimethyl-7H-purine-2,6-dione) and caffeine (1,3,7-trimethylxanthine). Theophylline, also known as 1,3-dimethylxanthine is being used as a bronchodilator drug in pulmonary diseases such as asthma or chronic pulmonary obstructive disease (COPD).…”

Section: Introductionmentioning

confidence: 99%

“…Theophylline, also known as 1,3-dimethylxanthine is being used as a bronchodilator drug in pulmonary diseases such as asthma or chronic pulmonary obstructive disease (COPD). 25 , 27 , 28 The main role of theophylline is acting as a non-specific adenosine antagonist, antagonizing A1, A2 and A3 receptors almost equally. 3 Investigated activities of theophylline derivatives, 7- and 8-positions include bronchospasmolytic 29 , 30 anticancer, antimicrobial and circulatory blood system activity.…”

Section: Introductionmentioning

confidence: 99%

Potential synergistic effect of phosphodiesterase inhibitors with chemotherapy in lung cancer

et al. 2017

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Purpose: Lung cancer remains the leading cause of cancer-related deaths worldwide and novel therapeutic approaches targeting crucial pathways are urgently needed to improve its treatment. Differentiation-based therapeutics (Methylxanthines) and phosphodiesterase inhibitors (type 4 and 5), have been implicated in cancer treatment. Our objectives were to capture any potential anti-tumor effect of these drug combinations with chemotherapeutic agents in vitro.Methods: Theophylline as Methylxanthines, Roflumilast as phosphodiesterase type 4 (PDE4) inhibitor and Sildenafil as phosphodiesterase type 5 (PDE5) inhibitor are the drugs that we combined with the chemotherapeutic agents (Docetaxel, Cisplatin and Carboplatin) in vitro. Lung cancer cell lines (NCI-H1048-Small cell lung cancer-SCLC, A549- Non-small cell lung cancer-NSCLC) were purchased from ATCC LGC Standards. At indicated time-point, following 24h and 48h incubation, cell viability and apoptosis were measured with Annexin V staining by flow cytometry. Statistical analysis was performed by GraphPad Prism.Results: In SCLC, following 48h incubation, platinum combinations of carboplatin with roflumilast and sildenafil (p<0.001) and carboplatin with theophylline and sildenafil showed increased apoptosis when compared to carboplatin alone. Concerning the combinations of cisplatin, when combined with roflumilast, theophylline and sildenafil appeared with increased apoptosis of that alone (p<0.001, 24h and 48h incubation). In NSCLC, the 24h incubation was not enough to induce satisfactory apoptosis, except for the combination of cisplatin with roflumilast and theophylline (p<0.05) when compared to cisplatin alone. However, following 48h incubation, carboplatin plus sildenafil, carboplatin plus sildenafil, theophylline and roflumilast showed more cytotoxicity when compared to carboplatin alone (p<0.001). Docetaxel combinations showed no statistically significant results.Conclusion: The synergistic effect of PDE inhibitors with platinum-based agents has been demonstrated in lung cancer. Our suggestion is that these combinations could be used as additive and maintenance treatment in combination to antineoplastic agents in lung cancer patients.

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Aminophylline for treating asthma and chronic obstructive pulmonary disease

Cited by 15 publications

References 64 publications

Adenosine A2B Receptor Blockade Slows Growth of Bladder and Breast Tumors

Adenosine A2B Receptor Blockade Slows Growth of Bladder and Breast Tumors

Effectiveness and Toxicity Risk of Intravenous Aminophylline in Exacerbation Asthma Treatment

Potential synergistic effect of phosphodiesterase inhibitors with chemotherapy in lung cancer

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