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Theophylline

January 01, 1970

Theophylline, also known as 1,3-dimethylxanthine, is a drug that inhibits phosphodiesterase and blocks adenosine receptors.[1] It is used to treat chronic obstructive pulmonary disease (COPD) and asthma.[2] Its pharmacology is similar to other methylxanthine drugs (e.g., theobromine and caffeine).[1] Trace amounts of theophylline are naturally present in tea, coffee, chocolate, yerba maté, guarana, and kola nut.[1][3]

Theophylline
Clinical data
Trade namesTheolair, Slo-Bid
AHFS/Drugs.comMonograph
MedlinePlusa681006
Pregnancy
category
Routes of
administration		oral, IV, rectal
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability100% (oral)
Protein binding40% (primarily to albumin)
MetabolismHepatic: CYP1A2, CYP2E1, CYP3A4
Metabolites• 1,3-Dimethyluric acid
• 1-Methyixanthine
• 3-Methylxanthine
Elimination half-life5–8 hours
Identifiers
  • 1,3-dimethyl-7H-purine-2,6-dione
CAS Number
  • 58-55-9 Y
PubChem CID
  • 2153
IUPHAR/BPS
  • 413
DrugBank
  • DB00277 Y
ChemSpider
  • 2068 Y
UNII
  • 0I55128JYK
KEGG
  • D00371 Y
ChEBI
  • CHEBI:28177 Y
ChEMBL
  • ChEMBL190 Y
CompTox Dashboard (EPA)
  • DTXSID5021336
ECHA InfoCard100.000.350
Chemical and physical data
FormulaC7H8N4O2
Molar mass180.167 g·mol−1
3D model (JSmol)
  • Interactive image
  • Cn1c2c(c(=O)n(c1=O)C)[nH]cn2
  • InChI=1S/C7H8N4O2/c1-10-5-4(8-3-9-5)6(12)11(2)7(10)13/h3H,1-2H3,(H,8,9) Y
  • Key:ZFXYFBGIUFBOJW-UHFFFAOYSA-N Y
  (verify)
Theophylline extended-release tablets in Japan

The name 'theophylline' derives from "Thea"—the former genus name for tea + Legacy Greek φύλλον (phúllon, "leaf") + -ine.

Medical uses edit

The main actions of theophylline involve:[2]

The main therapeutic uses of theophylline are for treating:[2]

Performance enhancement in sports edit

Theophylline and other methylxanthines are often used for their performance-enhancing effects in sports, as these drugs increase alertness, bronchodilation, and increase the rate and force of heart contraction.[9] There is conflicting information about the value of theophylline and other methylxanthines as prophylaxis against exercise-induced asthma.[10]

Adverse effects edit

The use of theophylline is complicated by its interaction with various drugs and by the fact that it has a narrow therapeutic window (<20 mcg/mL).[2] Its use must be monitored by direct measurement of serum theophylline levels to avoid toxicity. It can also cause nausea, diarrhea, increase in heart rate, abnormal heart rhythms, and CNS excitation (headaches, insomnia, irritability, dizziness and lightheadedness).[2][11] Seizures can also occur in severe cases of toxicity, and are considered to be a neurological emergency.[2]

Its toxicity is increased by erythromycin, cimetidine, and fluoroquinolones, such as ciprofloxacin. Some lipid-based formulations of theophylline can result in toxic theophylline levels when taken with fatty meals, an effect called dose dumping, but this does not occur with most formulations of theophylline.[12] Theophylline toxicity can be treated with beta blockers. In addition to seizures, tachyarrhythmias are a major concern.[13] Theophylline should not be used in combination with the SSRI fluvoxamine.[14][15]

Spectroscopy edit

UV-visible spectroscopy edit

Theophylline is soluble in 0.1N NaOH and absorbs maximally at 277 nm with an extinction coefficient of 10,200 (cm−1 M−1).[16]

Proton nuclear magnetic resonance spectroscopy (1H-NMR) edit

The characteristic signals, distinguishing theophylline from related methylxanthines, are approximately 3.23δ and 3.41δ, corresponding to the unique methylation possessed by theophylline. The remaining proton signal, at 8.01δ, corresponds to the proton on the imidazole ring, not transferred between the nitrogen. The transferred proton between the nitrogen is a variable proton and only exhibits a signal under certain conditions.[17]

Carbon nuclear magnetic resonance spectroscopy (13C-NMR) edit

The unique methylation of theophylline corresponds to the following signals: 27.7δ and 29.9δ. The remaining signals correspond to carbons characteristic of the xanthine backbone.[18]

Natural occurrences edit

Theophylline is naturally found in cocoa beans. Amounts as high as 3.7 mg/g have been reported in Criollo cocoa beans.[19]

Trace amounts of theophylline are also found in brewed tea, although brewed tea provides only about 1 mg/L,[20] which is significantly less than a therapeutic dose.

Trace amounts of theophylline are also found in guarana (Paullinia cupana) and in kola nuts.[21]

Pharmacology edit

Pharmacodynamics edit

Like other methylated xanthine derivatives, theophylline is both a

  1. competitive nonselective phosphodiesterase inhibitor which increases intracellular levels of cAMP and cGMP,[2][22] activates PKA, inhibits TNF-alpha[23][24] and inhibits leukotriene[25] synthesis, and reduces inflammation and innate immunity[25]
  2. nonselective adenosine receptor antagonist, antagonizing A1, A2, and A3 receptors almost equally, which explains many of its cardiac effects.[2][26] Theophylline activates histone deacetylases.[2]

Pharmacokinetics edit

Absorption edit

When theophylline is administered intravenously, bioavailability is 100%.[27]

Distribution edit

Theophylline is distributed in the extracellular fluid, in the placenta, in the mother's milk and in the central nervous system. The volume of distribution is 0.5 L/kg. The protein binding is 40%.[medical citation needed]

Metabolism edit

Theophylline is metabolized extensively in the liver.[2] It undergoes N-demethylation via cytochrome P450 1A2. It is metabolized by parallel first order and Michaelis-Menten pathways. Metabolism may become saturated (non-linear), even within the therapeutic range. Small dose increases may result in disproportionately large increases in serum concentration. Methylation to caffeine is also important in the infant population. Smokers and people with hepatic (liver) impairment metabolize it differently.[2] Cigarette and marijuana smoking induces metabolism of theophylline, increasing the drug's metabolic clearance.[28][29]

Excretion edit

Theophylline is excreted unchanged in the urine (up to 10%). Clearance of the drug is increased in children (age 1 to 12), teenagers (12 to 16), adult smokers, elderly smokers, as well as in cystic fibrosis, and hyperthyroidism. Clearance of the drug is decreased in these conditions: elderly, acute congestive heart failure, cirrhosis, hypothyroidism and febrile viral illnesses.[2]

The elimination half-life varies: 30 hours for premature neonates, 24 hours for neonates, 3.5 hours for children ages 1 to 9, 8 hours for adult non-smokers, 5 hours for adult smokers, 24 hours for those with hepatic impairment, 12 hours for those with congestive heart failure NYHA class I-II, 24 hours for those with congestive heart failure NYHA class III-IV, 12 hours for the elderly.[medical citation needed]

History edit

Theophylline was first extracted from tea leaves and chemically identified around 1888 by the German biologist Albrecht Kossel.[30][31] Seven years later, a chemical synthesis starting with 1,3-dimethyluric acid was described by Emil Fischer and Lorenz Ach.[32] The Traube purine synthesis, an alternative method to synthesize theophylline, was introduced in 1900 by another German scientist, Wilhelm Traube.[33] Theophylline's first clinical use came in 1902 as a diuretic.[34] It took an additional 20 years until it was first reported as an asthma treatment.[35] The drug was prescribed in a syrup up to the 1970s as Theostat 20 and Theostat 80, and by the early 1980s in a tablet form called Quibron.

References edit

  1. ^ a b c "Theophylline". PubChem, US National Library of Medicine. 26 August 2023. Retrieved 2 September 2023.
  2. ^ a b c d e f g h i j k l Barnes PJ (October 2013). "Theophylline". American Journal of Respiratory and Critical Care Medicine. 188 (8): 901–906. doi:10.1164/rccm.201302-0388PP. PMID 23672674.
  3. ^ IARC Working Group on the Evaluation of Carcinogenic Risks to Humans (1991). "Coffee, Tea, Mate, Methylxanthines and Methylglyoxal". IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. 51. International Agency for Research on Cancer: 391–419. PMC 7681294. PMID 2033791.
  4. ^ Eldridge FL, Millhorn DE, Kiley JP (November 1985). "Antagonism by theophylline of respiratory inhibition induced by adenosine". Journal of Applied Physiology. 59 (5): 1428–1433. doi:10.1152/jappl.1985.59.5.1428. PMID 4066573.
  5. ^ Mahemuti G, Zhang H, Li J, Tieliwaerdi N, Ren L (10 January 2018). "Efficacy and side effects of intravenous theophylline in acute asthma: a systematic review and meta-analysis". Drug Design, Development and Therapy. 12: 99–120. doi:10.2147/DDDT.S156509. PMC 5768195. PMID 29391776.
  6. ^ Miao Y, Zhou Y, Zhao S, et al. (19 September 2022). "Comparative efficacy and safety of caffeine citrate and aminophylline in treating apnea of prematurity: A systematic review and meta-analysis". PLOS ONE. 17 (9): e0274882. Bibcode:2022PLoSO..1774882M. doi:10.1371/journal.pone.0274882. PMC 9484669. PMID 36121807.
  7. ^ Hung KC, Ho CN, Chen IW, Hung IY, Lin MC, Lin CM, et al. (August 2021). "The impact of aminophylline on incidence and severity of post-dural puncture headache: A meta-analysis of randomised controlled trials". Anaesthesia, Critical Care & Pain Medicine. 40 (4): 100920. doi:10.1016/j.accpm.2021.100920. PMID 34186265. S2CID 235686558.
  8. ^ Barati-Boldaji R, Shojaei-Zarghani S, Mehrabi M, Amini A, Safarpour AR (April 2023). "Post-dural puncture headache prevention and treatment with aminophylline or theophylline: a systematic review and meta-analysis". Anesthesia and Pain Medicine. 18 (2): 177–189. doi:10.17085/apm.22247. PMC 10183611. PMID 37183286.
  9. ^ Watson CJ, Stone GL, Overbeek DL, Chiba T, Burns MM (February 2022). "Performance-enhancing drugs and the Olympics". Journal of Internal Medicine. 291 (2): 181–196. doi:10.1111/joim.13431. PMID 35007384. S2CID 245855348.
  10. ^ Pigakis KM, Stavrou VT, Pantazopoulos I, Daniil Z, Kontopodi AK, Gourgoulianis K (January 2022). "Exercise-Induced Bronchospasm in Elite Athletes". Cureus. 14 (1): e20898. doi:10.7759/cureus.20898. PMC 8807463. PMID 35145802.
  11. ^ . MedlinePlus Drug Information. U.S. National Library of Medicine. Archived from the original on July 5, 2016.
  12. ^ Hendeles L, Weinberger M, Milavetz G, Hill M, Vaughan L (June 1985). "Food-induced "dose-dumping" from a once-a-day theophylline product as a cause of theophylline toxicity". Chest. 87 (6): 758–765. doi:10.1378/chest.87.6.758. PMID 3996063. S2CID 1133968.
  13. ^ Seneff M, Scott J, Friedman B, Smith M (June 1990). "Acute theophylline toxicity and the use of esmolol to reverse cardiovascular instability". Annals of Emergency Medicine. 19 (6): 671–673. doi:10.1016/s0196-0644(05)82474-6. PMID 1971502.
  14. ^ DeVane CL, Markowitz JS, Hardesty SJ, Mundy S, Gill HS (September 1997). "Fluvoxamine-induced theophylline toxicity". The American Journal of Psychiatry. 154 (9): 1317–1318. doi:10.1176/ajp.154.9.1317b. PMID 9286199.
  15. ^ Sperber AD (November 1991). "Toxic interaction between fluvoxamine and sustained release theophylline in an 11-year-old boy". Drug Safety. 6 (6): 460–462. doi:10.2165/00002018-199106060-00006. PMID 1793525. S2CID 21875026.
  16. ^ Schack JA, Waxler SH (November 1949). "An ultraviolet spectrophotometric method for the determination of theophylline and theobromine in blood and tissues". The Journal of Pharmacology and Experimental Therapeutics. 97 (3): 283–291. PMID 15392550.
  17. ^ Shelke RU, Degani MS, Raju A, Ray MK, Rajan MG (August 2016). "Fragment Discovery for the Design of Nitrogen Heterocycles as Mycobacterium tuberculosis Dihydrofolate Reductase Inhibitors". Archiv der Pharmazie. 349 (8): 602–613. doi:10.1002/ardp.201600066. PMID 27320965. S2CID 40014874.
  18. ^ Pfleiderer W (February 2008). "Pteridines. Part CXIX. A New Pteridine–Purine Transformation". Helvetica Chimica Acta. 91 (2): 338–353. doi:10.1002/hlca.200890039.
  19. ^ Apgar JL, Tarka Jr SM (1998). "Methylxanthine composition and consumption patterns of cocoa and chocolate products and their uses". In Spiller GA (ed.). Caffeine. CRC Press. p. 171. ISBN 978-0-8493-2647-9. Retrieved 2013-11-10.
  20. ^ . Food Surveillance Information Sheet Number 103. MAFF, Department of Health and the Scottish Executive. Archived from the original on 2006-09-27.
  21. ^ Belliardo F, Martelli A, Valle MG (May 1985). "HPLC determination of caffeine and theophylline in Paullinia cupana Kunth (guarana) and Cola spp. samples". Zeitschrift für Lebensmittel-Untersuchung und -Forschung. 180 (5): 398–401. doi:10.1007/BF01027774. PMID 4013524. S2CID 40205323.
  22. ^ Essayan DM (November 2001). "Cyclic nucleotide phosphodiesterases". The Journal of Allergy and Clinical Immunology. 108 (5): 671–680. doi:10.1067/mai.2001.119555. PMID 11692087.
  23. ^ Deree J, Martins JO, Melbostad H, Loomis WH, Coimbra R (June 2008). "Insights into the regulation of TNF-alpha production in human mononuclear cells: the effects of non-specific phosphodiesterase inhibition". Clinics. 63 (3): 321–328. doi:10.1590/S1807-59322008000300006. PMC 2664230. PMID 18568240.
  24. ^ Marques LJ, Zheng L, Poulakis N, Guzman J, Costabel U (February 1999). "Pentoxifylline inhibits TNF-alpha production from human alveolar macrophages". American Journal of Respiratory and Critical Care Medicine. 159 (2): 508–511. doi:10.1164/ajrccm.159.2.9804085. PMID 9927365.
  25. ^ a b Peters-Golden M, Canetti C, Mancuso P, Coffey MJ (January 2005). "Leukotrienes: underappreciated mediators of innate immune responses". Journal of Immunology. 174 (2): 589–594. doi:10.4049/jimmunol.174.2.589. PMID 15634873.
  26. ^ Daly JW, Jacobson KA, Ukena D (1987). "Adenosine receptors: development of selective agonists and antagonists". Progress in Clinical and Biological Research. 230 (1): 41–63. PMID 3588607.
  27. ^ Griffin JP (2009). The Textbook of Pharmaceutical Medicine (6th ed.). Chichester: Wiley-Blackwell. ISBN 978-1-4051-8035-1.
  28. ^ Jenne JW, Nagasawa HT, Thompson RD (March 1976). "Relationship of urinary metabolites of theophylline to serum theophylline levels". Clinical Pharmacology and Therapeutics. 19 (3): 375–381. doi:10.1002/cpt1976193375. PMID 1261172. S2CID 33943915.
  29. ^ Jusko WJ, Schentag JJ, Clark JH, Gardner M, Yurchak AM (October 1978). "Enhanced biotransformation of theophylline in marihuana and tobacco smokers". Clinical Pharmacology and Therapeutics. 24 (4): 405–410. doi:10.1002/cpt1978244406. PMID 688731. S2CID 44613672.
  30. ^ Kossel A (1888). "Über eine neue Base aus dem Pflanzenreich" [About a new base from the plant kingdom]. Berichte der Deutschen Chemischen Gesellschaft [Reports of the German Chemical Society] (in German). 21: 2164–2167. doi:10.1002/cber.188802101422.
  31. ^ Kossel A (1889). "Über das Theophyllin, einen neuen Bestandtheil des Thees" [On theophylline, a new component of tea]. Hoppe-Seyler's Zeitschrift für Physiologische Chemie [Hoppe-Seyler's Journal of Physiological Chemistry] (in German). 13: 298–308.
  32. ^ Fischer E, Ach L (1895). "Synthese des Caffeins" [Synthesis of caffeine]. Berichte der Deutschen Chemischen Gesellschaft [Reports of the German Chemical Society] (in German). 28 (3): 3139. doi:10.1002/cber.189502803156.
  33. ^ Traube W (1900). "Der synthetische Aufbau der Harnsäure, des Xanthins, Theobromins, Theophyllins und Caffeïns aus der Cyanessigsäure" [The synthetic structure of uric acid, xanthine, theobromine, theophylline and caffeine from cyanoacetic acid]. Berichte der Deutschen Chemischen Gesellschaft [Reports of the German Chemical Society] (in German). 33 (3): 3035–3056. doi:10.1002/cber.19000330352.
  34. ^ Minkowski O (1902). "Über Theocin (Theophyllin) als Diureticum" [About theocine (theophylline) as a diuretic]. Therapie der Gegenwart [Therapy of the Present] (in German). 43: 490–493.
  35. ^ Schultze-Werninghaus G, Meier-Sydow J (March 1982). "The clinical and pharmacological history of theophylline: first report on the bronchospasmolytic action in man by S. R. Hirsch in Frankfurt (Main) 1922". Clinical Allergy. 12 (2): 211–215. doi:10.1111/j.1365-2222.1982.tb01641.x. PMID 7042115. S2CID 38178598.

External links edit

  •   Media related to Theophylline at Wikimedia Commons

January 01, 1970
theophylline, also, known, dimethylxanthine, drug, that, inhibits, phosphodiesterase, blocks, adenosine, receptors, used, treat, chronic, obstructive, pulmonary, disease, copd, asthma, pharmacology, similar, other, methylxanthine, drugs, theobromine, caffeine,. Theophylline also known as 1 3 dimethylxanthine is a drug that inhibits phosphodiesterase and blocks adenosine receptors 1 It is used to treat chronic obstructive pulmonary disease COPD and asthma 2 Its pharmacology is similar to other methylxanthine drugs e g theobromine and caffeine 1 Trace amounts of theophylline are naturally present in tea coffee chocolate yerba mate guarana and kola nut 1 3 TheophyllineClinical dataTrade namesTheolair Slo BidAHFS Drugs comMonographMedlinePlusa681006PregnancycategoryAU A citation needed Routes ofadministrationoral IV rectalATC codeR03DA04 WHO R03DB04Legal statusLegal statusAU S4 Prescription only CA only UK P Pharmacy medicines US onlyPharmacokinetic dataBioavailability100 oral Protein binding40 primarily to albumin MetabolismHepatic CYP1A2 CYP2E1 CYP3A4Metabolites 1 3 Dimethyluric acid 1 Methyixanthine 3 MethylxanthineElimination half life5 8 hoursIdentifiersIUPAC name 1 3 dimethyl 7H purine 2 6 dioneCAS Number58 55 9 YPubChem CID2153IUPHAR BPS413DrugBankDB00277 YChemSpider2068 YUNII0I55128JYKKEGGD00371 YChEBICHEBI 28177 YChEMBLChEMBL190 YCompTox Dashboard EPA DTXSID5021336ECHA InfoCard100 000 350Chemical and physical dataFormulaC 7H 8N 4O 2Molar mass180 167 g mol 13D model JSmol Interactive imageSMILES Cn1c2c c O n c1 O C nH cn2InChI InChI 1S C7H8N4O2 c1 10 5 4 8 3 9 5 6 12 11 2 7 10 13 h3H 1 2H3 H 8 9 YKey ZFXYFBGIUFBOJW UHFFFAOYSA N Y verify Theophylline extended release tablets in Japan The name theophylline derives from Thea the former genus name for tea Legacy Greek fyllon phullon leaf ine Contents 1 Medical uses 2 Performance enhancement in sports 3 Adverse effects 4 Spectroscopy 4 1 UV visible spectroscopy 4 2 Proton nuclear magnetic resonance spectroscopy 1H NMR 4 3 Carbon nuclear magnetic resonance spectroscopy 13C NMR 5 Natural occurrences 6 Pharmacology 6 1 Pharmacodynamics 6 2 Pharmacokinetics 6 2 1 Absorption 6 2 2 Distribution 6 2 3 Metabolism 6 2 4 Excretion 7 History 8 References 9 External linksMedical uses editThe main actions of theophylline involve 2 relaxing bronchial smooth muscle increasing heart muscle contractility and efficiency positive inotrope increasing heart rate positive chronotropic increasing blood pressure increasing renal blood flow anti inflammatory effects central nervous system stimulatory effect mainly on the medullary respiratory center 4 The main therapeutic uses of theophylline are for treating 2 Chronic obstructive pulmonary disease COPD 5 Asthma infant apnea 6 Blocks the action of adenosine an inhibitory neurotransmitter that induces sleep contracts the smooth muscles and relaxes the cardiac muscle Treatment of post dural puncture headache 7 8 Performance enhancement in sports editTheophylline and other methylxanthines are often used for their performance enhancing effects in sports as these drugs increase alertness bronchodilation and increase the rate and force of heart contraction 9 There is conflicting information about the value of theophylline and other methylxanthines as prophylaxis against exercise induced asthma 10 Adverse effects editThe use of theophylline is complicated by its interaction with various drugs and by the fact that it has a narrow therapeutic window lt 20 mcg mL 2 Its use must be monitored by direct measurement of serum theophylline levels to avoid toxicity It can also cause nausea diarrhea increase in heart rate abnormal heart rhythms and CNS excitation headaches insomnia irritability dizziness and lightheadedness 2 11 Seizures can also occur in severe cases of toxicity and are considered to be a neurological emergency 2 Its toxicity is increased by erythromycin cimetidine and fluoroquinolones such as ciprofloxacin Some lipid based formulations of theophylline can result in toxic theophylline levels when taken with fatty meals an effect called dose dumping but this does not occur with most formulations of theophylline 12 Theophylline toxicity can be treated with beta blockers In addition to seizures tachyarrhythmias are a major concern 13 Theophylline should not be used in combination with the SSRI fluvoxamine 14 15 Spectroscopy editUV visible spectroscopy edit Theophylline is soluble in 0 1N NaOH and absorbs maximally at 277 nm with an extinction coefficient of 10 200 cm 1 M 1 16 Proton nuclear magnetic resonance spectroscopy 1H NMR edit The characteristic signals distinguishing theophylline from related methylxanthines are approximately 3 23d and 3 41d corresponding to the unique methylation possessed by theophylline The remaining proton signal at 8 01d corresponds to the proton on the imidazole ring not transferred between the nitrogen The transferred proton between the nitrogen is a variable proton and only exhibits a signal under certain conditions 17 Carbon nuclear magnetic resonance spectroscopy 13C NMR edit The unique methylation of theophylline corresponds to the following signals 27 7d and 29 9d The remaining signals correspond to carbons characteristic of the xanthine backbone 18 Natural occurrences editTheophylline is naturally found in cocoa beans Amounts as high as 3 7 mg g have been reported in Criollo cocoa beans 19 Trace amounts of theophylline are also found in brewed tea although brewed tea provides only about 1 mg L 20 which is significantly less than a therapeutic dose Trace amounts of theophylline are also found in guarana Paullinia cupana and in kola nuts 21 Pharmacology editPharmacodynamics edit Like other methylated xanthine derivatives theophylline is both a competitive nonselective phosphodiesterase inhibitor which increases intracellular levels of cAMP and cGMP 2 22 activates PKA inhibits TNF alpha 23 24 and inhibits leukotriene 25 synthesis and reduces inflammation and innate immunity 25 nonselective adenosine receptor antagonist antagonizing A1 A2 and A3 receptors almost equally which explains many of its cardiac effects 2 26 Theophylline activates histone deacetylases 2 Pharmacokinetics edit Absorption edit When theophylline is administered intravenously bioavailability is 100 27 Distribution edit Theophylline is distributed in the extracellular fluid in the placenta in the mother s milk and in the central nervous system The volume of distribution is 0 5 L kg The protein binding is 40 medical citation needed Metabolism edit Theophylline is metabolized extensively in the liver 2 It undergoes N demethylation via cytochrome P450 1A2 It is metabolized by parallel first order and Michaelis Menten pathways Metabolism may become saturated non linear even within the therapeutic range Small dose increases may result in disproportionately large increases in serum concentration Methylation to caffeine is also important in the infant population Smokers and people with hepatic liver impairment metabolize it differently 2 Cigarette and marijuana smoking induces metabolism of theophylline increasing the drug s metabolic clearance 28 29 Excretion edit Theophylline is excreted unchanged in the urine up to 10 Clearance of the drug is increased in children age 1 to 12 teenagers 12 to 16 adult smokers elderly smokers as well as in cystic fibrosis and hyperthyroidism Clearance of the drug is decreased in these conditions elderly acute congestive heart failure cirrhosis hypothyroidism and febrile viral illnesses 2 The elimination half life varies 30 hours for premature neonates 24 hours for neonates 3 5 hours for children ages 1 to 9 8 hours for adult non smokers 5 hours for adult smokers 24 hours for those with hepatic impairment 12 hours for those with congestive heart failure NYHA class I II 24 hours for those with congestive heart failure NYHA class III IV 12 hours for the elderly medical citation needed History editTheophylline was first extracted from tea leaves and chemically identified around 1888 by the German biologist Albrecht Kossel 30 31 Seven years later a chemical synthesis starting with 1 3 dimethyluric acid was described by Emil Fischer and Lorenz Ach 32 The Traube purine synthesis an alternative method to synthesize theophylline was introduced in 1900 by another German scientist Wilhelm Traube 33 Theophylline s first clinical use came in 1902 as a diuretic 34 It took an additional 20 years until it was first reported as an asthma treatment 35 The drug was prescribed in a syrup up to the 1970s as Theostat 20 and Theostat 80 and by the early 1980s in a tablet form called Quibron References edit a b c Theophylline PubChem US National Library of Medicine 26 August 2023 Retrieved 2 September 2023 a b c d e f g h i j k l Barnes PJ October 2013 Theophylline American Journal of Respiratory and Critical Care Medicine 188 8 901 906 doi 10 1164 rccm 201302 0388PP PMID 23672674 IARC Working Group on the Evaluation of Carcinogenic Risks to Humans 1991 Coffee Tea Mate Methylxanthines and Methylglyoxal IARC Monographs on the Evaluation of Carcinogenic Risks to Humans 51 International Agency for Research on Cancer 391 419 PMC 7681294 PMID 2033791 Eldridge FL Millhorn DE Kiley JP November 1985 Antagonism by theophylline of respiratory inhibition induced by adenosine Journal of Applied Physiology 59 5 1428 1433 doi 10 1152 jappl 1985 59 5 1428 PMID 4066573 Mahemuti G Zhang H Li J Tieliwaerdi N Ren L 10 January 2018 Efficacy and side effects of intravenous theophylline in acute asthma a systematic review and meta analysis Drug Design Development and Therapy 12 99 120 doi 10 2147 DDDT S156509 PMC 5768195 PMID 29391776 Miao Y Zhou Y Zhao S et al 19 September 2022 Comparative efficacy and safety of caffeine citrate and aminophylline in treating apnea of prematurity A systematic review and meta analysis PLOS ONE 17 9 e0274882 Bibcode 2022PLoSO 1774882M doi 10 1371 journal pone 0274882 PMC 9484669 PMID 36121807 Hung KC Ho CN Chen IW Hung IY Lin MC Lin CM et al August 2021 The impact of aminophylline on incidence and severity of post dural puncture headache A meta analysis of randomised controlled trials Anaesthesia Critical Care amp Pain Medicine 40 4 100920 doi 10 1016 j accpm 2021 100920 PMID 34186265 S2CID 235686558 Barati Boldaji R Shojaei Zarghani S Mehrabi M Amini A Safarpour AR April 2023 Post dural puncture headache prevention and treatment with aminophylline or theophylline a systematic review and meta analysis Anesthesia and Pain Medicine 18 2 177 189 doi 10 17085 apm 22247 PMC 10183611 PMID 37183286 Watson CJ Stone GL Overbeek DL Chiba T Burns MM February 2022 Performance enhancing drugs and the Olympics Journal of Internal Medicine 291 2 181 196 doi 10 1111 joim 13431 PMID 35007384 S2CID 245855348 Pigakis KM Stavrou VT Pantazopoulos I Daniil Z Kontopodi AK Gourgoulianis K January 2022 Exercise Induced Bronchospasm in Elite Athletes Cureus 14 1 e20898 doi 10 7759 cureus 20898 PMC 8807463 PMID 35145802 Theophylline MedlinePlus Drug Information U S National Library of Medicine Archived from the original on July 5 2016 Hendeles L Weinberger M Milavetz G Hill M Vaughan L June 1985 Food induced dose dumping from a once a day theophylline product as a cause of theophylline toxicity Chest 87 6 758 765 doi 10 1378 chest 87 6 758 PMID 3996063 S2CID 1133968 Seneff M Scott J Friedman B Smith M June 1990 Acute theophylline toxicity and the use of esmolol to reverse cardiovascular instability Annals of Emergency Medicine 19 6 671 673 doi 10 1016 s0196 0644 05 82474 6 PMID 1971502 DeVane CL Markowitz JS Hardesty SJ Mundy S Gill HS September 1997 Fluvoxamine induced theophylline toxicity The American Journal of Psychiatry 154 9 1317 1318 doi 10 1176 ajp 154 9 1317b PMID 9286199 Sperber AD November 1991 Toxic interaction between fluvoxamine and sustained release theophylline in an 11 year old boy Drug Safety 6 6 460 462 doi 10 2165 00002018 199106060 00006 PMID 1793525 S2CID 21875026 Schack JA Waxler SH November 1949 An ultraviolet spectrophotometric method for the determination of theophylline and theobromine in blood and tissues The Journal of Pharmacology and Experimental Therapeutics 97 3 283 291 PMID 15392550 Shelke RU Degani MS Raju A Ray MK Rajan MG August 2016 Fragment Discovery for the Design of Nitrogen Heterocycles as Mycobacterium tuberculosis Dihydrofolate Reductase Inhibitors Archiv der Pharmazie 349 8 602 613 doi 10 1002 ardp 201600066 PMID 27320965 S2CID 40014874 Pfleiderer W February 2008 Pteridines Part CXIX A New Pteridine Purine Transformation Helvetica Chimica Acta 91 2 338 353 doi 10 1002 hlca 200890039 Apgar JL Tarka Jr SM 1998 Methylxanthine composition and consumption patterns of cocoa and chocolate products and their uses In Spiller GA ed Caffeine CRC Press p 171 ISBN 978 0 8493 2647 9 Retrieved 2013 11 10 TABLE 2a Concentrations of caffeine theobromine and theophylline in tea products Food Surveillance Information Sheet Number 103 MAFF Department of Health and the Scottish Executive Archived from the original on 2006 09 27 Belliardo F Martelli A Valle MG May 1985 HPLC determination of caffeine and theophylline in Paullinia cupana Kunth guarana and Cola spp samples Zeitschrift 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jimmunol 174 2 589 PMID 15634873 Daly JW Jacobson KA Ukena D 1987 Adenosine receptors development of selective agonists and antagonists Progress in Clinical and Biological Research 230 1 41 63 PMID 3588607 Griffin JP 2009 The Textbook of Pharmaceutical Medicine 6th ed Chichester Wiley Blackwell ISBN 978 1 4051 8035 1 Jenne JW Nagasawa HT Thompson RD March 1976 Relationship of urinary metabolites of theophylline to serum theophylline levels Clinical Pharmacology and Therapeutics 19 3 375 381 doi 10 1002 cpt1976193375 PMID 1261172 S2CID 33943915 Jusko WJ Schentag JJ Clark JH Gardner M Yurchak AM October 1978 Enhanced biotransformation of theophylline in marihuana and tobacco smokers Clinical Pharmacology and Therapeutics 24 4 405 410 doi 10 1002 cpt1978244406 PMID 688731 S2CID 44613672 Kossel A 1888 Uber eine neue Base aus dem Pflanzenreich About a new base from the plant kingdom Berichte der Deutschen Chemischen Gesellschaft Reports of the German Chemical Society in German 21 2164 2167 doi 10 1002 cber 188802101422 Kossel A 1889 Uber das Theophyllin einen neuen Bestandtheil des Thees On theophylline a new component of tea Hoppe Seyler s Zeitschrift fur Physiologische Chemie Hoppe Seyler s Journal of Physiological Chemistry in German 13 298 308 Fischer E Ach L 1895 Synthese des Caffeins Synthesis of caffeine Berichte der Deutschen Chemischen Gesellschaft Reports of the German Chemical Society in German 28 3 3139 doi 10 1002 cber 189502803156 Traube W 1900 Der synthetische Aufbau der Harnsaure des Xanthins Theobromins Theophyllins und Caffeins aus der Cyanessigsaure The synthetic structure of uric acid xanthine theobromine theophylline and caffeine from cyanoacetic acid Berichte der Deutschen Chemischen Gesellschaft Reports of the German Chemical Society in German 33 3 3035 3056 doi 10 1002 cber 19000330352 Minkowski O 1902 Uber Theocin Theophyllin als Diureticum About theocine theophylline as a diuretic Therapie der Gegenwart Therapy of the Present in German 43 490 493 Schultze Werninghaus G Meier Sydow J March 1982 The clinical and pharmacological history of theophylline first report on the bronchospasmolytic action in man by S R Hirsch in Frankfurt Main 1922 Clinical Allergy 12 2 211 215 doi 10 1111 j 1365 2222 1982 tb01641 x PMID 7042115 S2CID 38178598 External links edit nbsp Media related to Theophylline at Wikimedia Commons Retrieved from https en wikipedia org w index php title Theophylline amp oldid 1226084651, wikipedia, wiki, book, books, library,

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