Information about Theophylline
Theophylline, also known as dimethylxanthine, is a methylxanthine drug used in therapy for respiratory diseases such as COPD or asthma under a variety of brand names. Due to its numerous side effects, these drugs are now rarely used clinically. As a member of the xanthine family, it bears structural and pharmacological similarity to caffeine. It is naturally found in tea, although in trace quantities (~1mg/l)[1], significantly less than therapeutic doses[2].
The main actions of theophylline are:
Theophylline has been shown to inhibit TGF-beta mediated conversion of pulmonary fibroblasts into myofibroblasts in COPD and asthma via cAMP-PKA pathway and suppresses COL1 mRNA which codes for the protein collagen. (Yano, Biochem and Biophys Res Comm V341-3, 2006)
It has been shown that theophylline may reverse the clinical observations of steroid insensitivity in patients with COPD and asthmatics who are active smokers (a condition resulting in oxidative stress) via a distinctly separate mechanism. Theophylline in vitro can restore the reduced HDAC (histone deacetylase) activity that is induced by oxidative stress (i.e. in smokers), returning steroid responsiveness toward normal (Ito et al., 2002a). Furthermore, theophylline has been shown to directly activate HDAC2 (Ito et al., 2002b). (Corticosteroids switch off the inflammatory response by blocking the expression of inflammatory mediators through deacetylation of histones, an effect mediated via histone deacetylase-2 (HDAC2). Once deacetylated, DNA is rewound around histones and repackaged so that the promoter regions of inflammatory genes are unavailable for binding of transcription factors such as NFB that act to turn on inflammatory activity. It has recently been shown that the oxidative stress associated with cigarette smoke can inhibit the activity of HDAC2, thereby blocking the anti-inflammatory effects of corticosteroids.) Thus theophylline could prove to be a novel form of adjunct therapy in improving the clinical response to steroids in smoking asthmatics.
Xanthine (IPA: /ˈzænθiːn, ˈzænθaɪn]/
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Xanthine (IPA: /ˈzænθiːn, ˈzænθaɪn]/
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Chronotropic effects (from chrono-, meaning time) are those that change the heart rate.
Chronotropic drugs may change the heart rate by affecting the nerves controlling the heart, or by changing the rhythm produced by the sinoatrial node.
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The main actions of theophylline are:
- relaxing of bronchial smooth muscle
- positive inotropic (increasing heart muscle contractility and efficiency)
- positive chronotropic (increasing heart rate)
- increase of blood pressure
- increase of renal blood flow
- some anti-inflammatory effects
- central nervous system stimulatory effect mainly on the medullary respiratory center.
History
Theophylline was first extracted from tea leaves around 1888 by the German biologist Albrecht Kossel. The drug was chemically identified in 1896 and eventually it was synthesized by another German scientist, Wilhelm Traube. Theophylline's first clinical use in asthma treatment came in the 1950s.Metabolism
It is metabolised in the liver. Smokers and people with hepatic (liver) impairment metabolize it differently.Indications
The main therapeutic uses of theophylline are:- chronic obstructive diseases of the airways
- chronic obstructive pulmonary disease (COPD)
- bronchial asthma.
Mechanisms of Action
A proposed mechanism of action includes a non-specific inhibition of phosphodiesterase enzymes, producing an increase in intracellular cyclic AMP; however, this is not known with certainty.[1][2][3]Theophylline has been shown to inhibit TGF-beta mediated conversion of pulmonary fibroblasts into myofibroblasts in COPD and asthma via cAMP-PKA pathway and suppresses COL1 mRNA which codes for the protein collagen. (Yano, Biochem and Biophys Res Comm V341-3, 2006)
It has been shown that theophylline may reverse the clinical observations of steroid insensitivity in patients with COPD and asthmatics who are active smokers (a condition resulting in oxidative stress) via a distinctly separate mechanism. Theophylline in vitro can restore the reduced HDAC (histone deacetylase) activity that is induced by oxidative stress (i.e. in smokers), returning steroid responsiveness toward normal (Ito et al., 2002a). Furthermore, theophylline has been shown to directly activate HDAC2 (Ito et al., 2002b). (Corticosteroids switch off the inflammatory response by blocking the expression of inflammatory mediators through deacetylation of histones, an effect mediated via histone deacetylase-2 (HDAC2). Once deacetylated, DNA is rewound around histones and repackaged so that the promoter regions of inflammatory genes are unavailable for binding of transcription factors such as NFB that act to turn on inflammatory activity. It has recently been shown that the oxidative stress associated with cigarette smoke can inhibit the activity of HDAC2, thereby blocking the anti-inflammatory effects of corticosteroids.) Thus theophylline could prove to be a novel form of adjunct therapy in improving the clinical response to steroids in smoking asthmatics.
Side effects
The use of theophylline is complicated by the fact that it interacts with various drugs, chiefly cimetidine and phenytoin, and that it has a narrow therapeutic index, so its use must be monitored to avoid toxicity. It can also cause nausea, diarrhea, increase in heart rate, arrhythmias and CNS excitation. Its toxicity is increased by erythromycin, cimetidine and fluoroquinolones.Synthesis
References
External links
Drugs for obstructive airway diseases: asthma/COPD (R03) | |
|---|---|
| Adrenergics, inhalants | Short acting β2-agonists: Salbutamol • Fenoterol • Terbutaline Long acting β2-agonists (LABA): Bambuterol • Clenbuterol • Formoterol • Salmeterol other: Epinephrine • Isoproterenol • Orciprenaline |
| Glucocorticoids | Beclometasone • Budesonide • Ciclesonide • Fluticasone • Mometasone |
| Anticholinergics | Ipratropium • Tiotropium |
| Mast cell stabilizers | Cromoglicate • Nedocromil |
| Xanthines | Aminophylline • Theobromine • Theophylline |
| Leukotriene antagonists | Montelukast • Pranlukast • Zafirlukast |
| Combination products | Budesonide/formoterol • Fluticasone/salmeterol • Ipratropium/salbutamol |
Not to be confused with xanthene.
Xanthine (IPA: /ˈzænθiːn, ˈzænθaɪn]/
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Diseases of the mammalian Respiratory system are classified physiologically into obstructive (i.e. conditions which impede the rate of flow into and out of the lungs) and restrictive (i.e. conditions which cause a reduction in the functional volume of the lungs).
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Asthma
Classification & external resources
ICD-10 J 45.
ICD-9 493
OMIM 600807
DiseasesDB 1006
MedlinePlus 000141
eMedicine med/177 emerg/43
MeSH C08.127.
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Classification & external resources
ICD-10 J 45.
ICD-9 493
OMIM 600807
DiseasesDB 1006
MedlinePlus 000141
eMedicine med/177 emerg/43
MeSH C08.127.
..... Click the link for more information.
Not to be confused with xanthene.
Xanthine (IPA: /ˈzænθiːn, ˈzænθaɪn]/
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Caffeine is a xanthine alkaloid compound that acts as a psychoactive stimulant in humans. The word comes from the French term for coffee, café.
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Caffeine is a xanthine alkaloid compound that acts as a psychoactive stimulant in humans. The word comes from the French term for coffee, café.
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This page contains Chinese text.
Without proper rendering support, you may see question marks, boxes, or other symbols instead of Chinese characters.
Tea is a beverage made by steeping processed leaves, buds, or twigs of the tea bush, Camellia sinensisWithout proper rendering support, you may see question marks, boxes, or other symbols instead of Chinese characters.
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Smooth muscle is a type of non-striated muscle, found within the "walls" of hollow organs and elsewhere like the bladder and abdominal cavity, the uterus, male and female reproductive tracts, the gastrointestinal tract, the respiratory tract, the vasculature, the skin and the
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An inotrope (IPA: [ˈaɪnətrop]) is an agent which increases or decreases the force or energy of muscular contractions. Negatively inotropic agents weaken the force of muscular contractions.
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Chronotropic effects (from chrono-, meaning time) are those that change the heart rate.
Chronotropic drugs may change the heart rate by affecting the nerves controlling the heart, or by changing the rhythm produced by the sinoatrial node.
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Blood pressure (strictly speaking: vascular pressure) refers to the force exerted by circulating blood on the walls of blood vessels, and constitutes one of the principal vital signs.
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The kidneys are organs that filter wastes (such as urea) from the blood and excrete them, along with water, as urine. The medical field that studies the kidneys and diseases of the kidney is called nephrology[1].
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Inflammation (Latin, inflammatio, to set on fire) is the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants.
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The central nervous system (CNS) represents the largest part of the nervous system, including the brain and the spinal cord. Together with the peripheral nervous system, it has a fundamental role in the control of behavior.
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Respiratory center (RC) is located in the medulla oblongata which is the lowermost part of the brain stem. RC receives controlling signals of neural, chemical and hormonal natures and controls the rate and depth of respiratory movements of the diaphragm and other respiratory
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Ludwig Karl Martin Leonhard Albrecht Kossel (September 16, 1853 – July 5, 1927) was a German medical doctor.
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Biography
Kossel was born in Rostock as the son of Prussian consul Albrecht Kossel and his wife Clara...... Click the link for more information.
Wilhelm Traube (10 January 1866 – 28 September 1942) was a German chemist.
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Biography
Traube was born at Ratibor (Racibórz) in Prussian Silesia, a son of the famous private scholar Moritz Traube...... Click the link for more information.
Asthma
Classification & external resources
ICD-10 J 45.
ICD-9 493
OMIM 600807
DiseasesDB 1006
MedlinePlus 000141
eMedicine med/177 emerg/43
MeSH C08.127.
..... Click the link for more information.
Classification & external resources
ICD-10 J 45.
ICD-9 493
OMIM 600807
DiseasesDB 1006
MedlinePlus 000141
eMedicine med/177 emerg/43
MeSH C08.127.
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The remainder of this article discusses the cyclic nucleotide phosphodiesterases:
The cyclic nucleotide phosphodiesterases (PDE) comprise a group of enzymes that degrade the phosphodiester bond in the second messenger molecules cAMP and cGMP.
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The cyclic nucleotide phosphodiesterases (PDE) comprise a group of enzymes that degrade the phosphodiester bond in the second messenger molecules cAMP and cGMP.
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Enzymes are proteins that catalyze (i.e. accelerate) chemical reactions.[1] In enzymatic reactions, the molecules at the beginning of the process are called substrates, and the enzyme converts them into different molecules, the products.
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Cyclic adenosine monophosphate (cAMP, cyclic AMP or 3'-5'-cyclic adenosine monophosphate) is a molecule that is important in many biological processes; it is derived from adenosine triphosphate (ATP).
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Transforming growth factor beta (TGF-β) is a protein that comes in three isoforms called TGF-β1, TGF-β2 and TGF-β3; it was also the original name for the founding member of this family that is now called TGF-β1.
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Asthma
Classification & external resources
ICD-10 J 45.
ICD-9 493
OMIM 600807
DiseasesDB 1006
MedlinePlus 000141
eMedicine med/177 emerg/43
MeSH C08.127.
..... Click the link for more information.
Classification & external resources
ICD-10 J 45.
ICD-9 493
OMIM 600807
DiseasesDB 1006
MedlinePlus 000141
eMedicine med/177 emerg/43
MeSH C08.127.
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Collagen is the main protein of connective tissue in animals and the most abundant protein in mammals, [1] making up about 25% of the total protein content.
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Uses
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Oxidative stress is caused by an imbalance between the production of reactive oxygen and a biological system's ability to readily detoxify the reactive intermediates or easily repair the resulting damage. All forms of life maintain a reducing environment within their cells.
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Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex. Corticosteroids are involved in a wide range of physiologic systems such as stress response, immune response and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood
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Cimetidine (INN) (IPA: [sɪˈmɛtədin, saɪ-]) is a histamine H2-receptor antagonist that inhibits the production of acid in the stomach.
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This article or section needs sources or references that appear in reliable, third-party publications. Alone, primary sources and sources affiliated with the subject of this article are not sufficient for an accurate encyclopedia article.
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The therapeutic index (also known as therapeutic ratio), is a comparison of the amount of a therapeutic agent that causes the therapeutic effect to the amount that causes toxic effects.
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Toxicity is the degree to which something is able to produce illness or damage to an exposed organism. Toxicity can refer to the effect on a whole organism, such as a human or a bacterium or a plant, or to a substructure, such as a cell (cytotoxicity) or an organ (organotoxicity
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Erythromycin is a macrolide antibiotic which has an antimicrobial spectrum similar to or slightly wider than that of penicillin, and is often used for people who have an allergy to penicillins.
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