Xanthines and Phosphodiesterase Inhibitors
- PMID: 27844172
- DOI: 10.1007/164_2016_71
Xanthines and Phosphodiesterase Inhibitors
Abstract
Theophylline is an orally acting xanthine that has been used since 1937 for the treatment of respiratory diseases including asthma and chronic obstructive pulmonary disease (COPD). However, in most treatment guidelines, xanthines have now been consigned to third-line therapy because of their narrow therapeutic window and propensity for drug-drug interactions. However, lower than conventional doses of theophylline considered to be bronchodilator are now known to have anti-inflammatory actions of relevance to the treatment of respiratory disease. The molecular mechanism(s) of action of theophylline are not well understood, but several potential targets have been suggested including non-selective inhibition of phosphodiesterases (PDE), inhibition of phosphoinositide 3-kinase, adenosine receptor antagonism and increased activity of certain histone deacetylases. Although theophylline has a narrow therapeutic window, other xanthines are in clinical use that are claimed to have a better tolerability such as doxofylline and bamifylline. Nonetheless, xanthines still play an important role in the treatment of asthma and COPD as they can show clinical benefit in patients who are refractory to glucocorticosteroid therapy, and withdrawal of xanthines from patients causes worsening of disease, even in patients taking concomitant glucocorticosteroids.More recently the orally active selective PDE4 inhibitor, roflumilast, has been introduced into clinical practice for the treatment of severe COPD on top of gold standard treatment. This drug has been shown to improve lung function in patients with severe COPD and to reduce exacerbations, but is dose limited by a range side effect, particularly gastrointestinal side effects.
Keywords: Adenosine receptor antagonism; Bamifylline; Doxofylline; HDAC; PI3δ-kinase; Phosphodiesterases; Theophylline.
Similar articles
-
The mechanism of action of doxofylline is unrelated to HDAC inhibition, PDE inhibition or adenosine receptor antagonism.Pulm Pharmacol Ther. 2012 Feb;25(1):55-61. doi: 10.1016/j.pupt.2011.10.007. Epub 2011 Nov 25. Pulm Pharmacol Ther. 2012. PMID: 22138191
-
Are phosphodiesterase 4 inhibitors just more theophylline?J Allergy Clin Immunol. 2006 Jun;117(6):1237-43. doi: 10.1016/j.jaci.2006.02.045. Epub 2006 May 3. J Allergy Clin Immunol. 2006. PMID: 16750981 Review.
-
Phosphodiesterase inhibitors for the treatment of asthma and chronic obstructive pulmonary disease.Int Arch Allergy Immunol. 2014;165(3):152-64. doi: 10.1159/000368800. Epub 2014 Dec 20. Int Arch Allergy Immunol. 2014. PMID: 25532037 Review.
-
Theophylline.Am J Respir Crit Care Med. 2013 Oct 15;188(8):901-6. doi: 10.1164/rccm.201302-0388PP. Am J Respir Crit Care Med. 2013. PMID: 23672674 Review.
-
The preclinical pharmacology of roflumilast--a selective, oral phosphodiesterase 4 inhibitor in development for chronic obstructive pulmonary disease.Pulm Pharmacol Ther. 2010 Aug;23(4):235-56. doi: 10.1016/j.pupt.2010.03.011. Epub 2010 Apr 7. Pulm Pharmacol Ther. 2010. PMID: 20381629 Review.
Cited by
-
Doxapram for the prevention and treatment of apnea in preterm infants.Cochrane Database Syst Rev. 2023 Oct 25;10(10):CD014145. doi: 10.1002/14651858.CD014145.pub2. Cochrane Database Syst Rev. 2023. PMID: 37877431 Review.
-
Antiplatelet Effects of Selected Xanthine-Based Adenosine A2A and A2B Receptor Antagonists Determined in Rat Blood.Int J Mol Sci. 2023 Aug 29;24(17):13378. doi: 10.3390/ijms241713378. Int J Mol Sci. 2023. PMID: 37686188 Free PMC article.
-
Effects of doxofylline as an adjuvant on severe exacerbation and long-term prognosis for COPD with different clinical subtypes.Clin Respir J. 2023 Sep;17(9):851-864. doi: 10.1111/crj.13670. Epub 2023 Aug 10. Clin Respir J. 2023. PMID: 37562435 Free PMC article. Clinical Trial.
-
Mucus Hypersecretion in Chronic Obstructive Pulmonary Disease and Its Treatment.Mediators Inflamm. 2023 Jul 6;2023:8840594. doi: 10.1155/2023/8840594. eCollection 2023. Mediators Inflamm. 2023. PMID: 37457746 Free PMC article. Review.
-
Could the serum glucose/potassium ratio offer an early reliable predictor of life-threatening events in acute methylxanthine intoxication?Toxicol Res (Camb). 2023 Mar 30;12(2):310-320. doi: 10.1093/toxres/tfad023. eCollection 2023 Apr. Toxicol Res (Camb). 2023. PMID: 37125326 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical