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'''Teofilin/efedrin''' ([[Nama NonproprietaryGenerik Internasional INNTooltip|INN]])<ref name="Mansfield1991" /> adalah formulasi kombinasi dosis tetap dari [[teofilin]], suatu antagonis reseptor [[adenosin,]]; dandengan [[efedrin]], suatu agen pelepas norepinefrin dan agen simpatomimetik yang bekerja secara tidak langsung,; yang telah digunakan sebagai [[bronkodilator]] dalam pengobatan [[asma]] dan sebagai [[dekongestan]] hidung.<ref name="Elks2014">{{cite book | vauthors = Elks J | title=The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies | publisher=Springer US | year=2014 | isbn=978-1-4757-2085-3 | url=https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA1179 | access-date=29 August 2024 | page=1179}}</ref><ref name="WHO-INN-1964">{{cite web | title=INN Proposed List 14 | website= World Health Organization (WHO) | date=31 October 1964 | url=https://www.who.int/publications/m/item/inn-pl-14 | ref={{sfnref | World Health Organization (WHO) | 1900}} | access-date=29 August 2024}}</ref><ref name="FederalRegister1978">{{cite book | author=National Archives (U.S.) | title=Federal Register | publisher=Office of the Federal Register, National Archives and Records Service, General Services Administration | issue=v. 43, nos. 57-63 | year=1978 | url=https://books.google.com/books?id=h-EVER6fsmAC&pg=PA12450 | language=de | access-date=30 August 2024 | pages=12450–12382}}</ref><ref name="SimsdoPicoReed1978">{{cite journal | vauthors = Sims JA, doPico GA, Reed CE | title = Bronchodilating effect of oral theophylline-ephedrine combination | journal = The Journal of Allergy and Clinical Immunology | volume = 62 | issue = 1 | pages = 15–21 | date = July 1978 | pmid = 350932 | doi = 10.1016/0091-6749(78)90066-0 }}</ref><ref name="WeinbergerBronskyBensch1975">{{cite journal | vauthors = Weinberger M, Bronsky E, Bensch GW, Bock GN, Yecies JJ | title = Interaction of ephedrine and theophylline | journal = Clinical Pharmacology and Therapeutics | volume = 17 | issue = 5 | pages = 585–592 | date = May 1975 | pmid = 1092514 | doi = 10.1002/cpt1975175585 | quote = Brown1 reported uncontrolled clinical observations suggesting the apparent effectiveness of a fixed dose combination of ephedrine and theophylline in 1940, Such preparations have become very popular, though a search of the literature since that initial report unearthed only one controlled study (of very limited scope) that suggested additive effect from drug combination.15 }}</ref><ref name="PinnasSchachtelChen1991">{{cite journal | vauthors = Pinnas JL, Schachtel BP, Chen TM, Roseberry HR, Thoden WR | title = Inhaled epinephrine and oral theophylline-ephedrine in the treatment of asthma | journal = Journal of Clinical Pharmacology | volume = 31 | issue = 3 | pages = 243–247 | date = March 1991 | pmid = 2019665 | doi = 10.1002/j.1552-4604.1991.tb04969.x }}</ref><ref name="StargroveTreasureMcKee2007">{{cite book | vauthors = Stargrove M, Treasure J, McKee D | title=Herb, Nutrient, and Drug Interactions: Clinical Implications and Therapeutic Strategies | publisher=Elsevier Health Sciences | year=2007 | isbn=978-0-323-02964-3 | url=https://books.google.com/books?id=49kLK--eumEC&pg=PA45 | access-date=2024-08-31 | page=45 | quote = Theophylline is generally more potent than caffeine in its effects; it was often combined with ephedrine in nasal decongestant products before more selective adrenergic blockers became available. An early study found the theophylline-ephedrine combination no more effective than theophylline alone in 23 asthmatic children, whereas the ADR rate was higher for the combination than for theophylline.40 Another study of asthmatic children, however, showed no additional adverse effects from the combination.}}</ref><ref name="Head2022">{{cite journal | vauthors = Head S | title=A breath of fresh air | journal=Prescriber | volume=33 | issue=2 | date=2022 | issn=0959-6682 | doi=10.1002/psb.1973 | pages=41–42 | quote = Amesec contained ephedrine and amylobarbitone with a whiff of aminophylline. Franol contained ephedrine and theophylline, and earlier versions also contained phenobarbital.}}</ref> Obat ini pertama kali dipelajari dan digunakan untuk mengobati asma pada tahun 1930-an atau 1940-an dan kombinasi kedua obat tersebut kemudian digunakan secara luas.<ref name="StargroveTreasureMcKee2007" /><ref name="WeinbergerBronskyBensch1975" /><ref name="WeinbergerHendeles1986">{{cite journal | vauthors = Weinberger M, Hendeles L | title = Therapeutic effect and dosing strategies for theophylline in the treatment of chronic asthma | journal = The Journal of Allergy and Clinical Immunology | volume = 78 | issue = 4 Pt 2 | pages = 762–768 | date = October 1986 | pmid = 3534057 | doi = 10.1016/0091-6749(86)90058-8 | quote = Theophylline has undergone a major transition in clinical use over the past 10 to 15 years. Used primarily for its cardiovascular effects in the early part of this century, theophylline was found in the 1920s to have clinically beneficial effects on acute bronchospasm.1 In the 1930s, theophylline became popular as an oral agent, particularly in fixed-dose combination with ephedrine. Its predominant use continued in this manner into the early 1970s. Since then, definition of the pharmacodynamics and pharmacokinetics of theophylline has led to its present use as a major prophylactic agent for the prevention of chronic asthma. }}</ref> Rasio teofilin dan efedrin 5:1 biasanya digunakan dalam kombinasi obat-obatan tersebut.<ref name="O'Loughlin1979">{{cite journal | vauthors = O'Loughlin JM | title = Drug therapy of bronchial asthma | journal = The Medical Clinics of North America | volume = 63 | issue = 2 | pages = 391–396 | date = March 1979 | pmid = 35721 | doi = }}</ref> Penelitian selanjutnya menemukan bahwa kombinasi tersebut tidak lebih efektif untuk asma daripada teofilin saja tetapi menghasilkan lebih banyak [[efek samping]].<ref name="StargroveTreasureMcKee2007" /><ref name="Mansfield1991" /><ref name="HendelesWeinberger1980" /><ref name="WeinbergerBronskyBensch1975" />
 
Kombinasi teofilin, efedrin, dan [[fenobarbital]] juga telah banyak digunakan untuk mengobati asma.<ref name="HendelesWeinberger1980">{{cite journal | vauthors = Hendeles L, Weinberger M | title = Avoidance of adverse effects during chronic therapy with theophylline | journal = European Journal of Respiratory Diseases. Supplement | volume = 109 | issue = | pages = 103–119 | date = 1980 | pmid = 7002576 | doi = | quote = Until recently, combination products containing theophylline, ephedrine, and a "sedative" were the most frequently prescribed bronchodilators in the United States. Several studies, however, have documented that the combination of ephedrine and theophylline produce synergistic toxicity without significantly enhancing the therapeutic efficacy of theophylline alone (Figure 1). }}</ref><ref name="KhouzamTanGill2007">{{cite book | vauthors = Khouzam H, Tan D, Gill T | title=Handbook of Emergency Psychiatry | publisher=Elsevier Health Sciences | year=2007 | isbn=978-0-323-07661-6 | url=https://books.google.com/books?id=Izob_Qe-EKwC&pg=PA53 | access-date=30 August 2024 | page=53}}</ref><ref name="Henzelman1972">{{cite book | vauthors = Heinzelman RV | title=Annual Reports in Medicinal Chemistry | publisher=Elsevier Science | series=ISSN | year=1972 | isbn=978-0-08-058351-8 | url=https://books.google.com/books?id=52joNWUvZakC&pg=PA92 | access-date=30 August 2024 | page=92}}</ref><ref name="ProjectLabel1979" /> Banyak kombinasi tersebut telah dipasarkan dengan berbagai nama merek. Teofilin juga telah dipasarkan dalam kombinasi dengan simpatomimetik serupa efedrin lainnya seperti [[rasefedrin]] dan [[pseudoefedrin]] serta dengan [[barbiturat]] lainnya seperti [[amobarbital]] dan [[butabarbital]].<ref name="ProjectLabel1979">{{cite book | title=Project Label: Alphabetical Listing by Drug Product | publisher=Department of Justice, Drug Enforcement Administration, Office of Compliance and Regulatory Affairs, Regulatory Support Division, Information Systems Section | year=1979 | url=https://books.google.com/books?id=8HJc_WTwdNsC | access-date=2024-08-31}}</ref> Kombinasi teofilin, efedrin, dan [[hidroksizin]] telah dipasarkan juga.<ref name="EmergMedCare1983">{{cite book | title=Emergency Medical Care: A Manual for the Paramedic in the Field | publisher=U.S. Department of Transportation, National Highway Traffic Safety Administration | series=Emergency Medical Care: A Manual for the Paramedic in the Field | issue=v. 1 | year=1983 | url=https://books.google.com/books?id=Ljgl1bvwKdwC&pg=RA3-PA33 | access-date=31 August 2024 | page=3-PA33}}</ref><ref name="EmergDepTrends2002">{{cite book | title=Emergency Department Trends from the Drug Abuse Warning Network: Preliminary Estimates January-June 2001 with Revised Estimates 1994-2000 | publisher=Department of Health and Human Services, Substance Abuse and Mental Health Services Administration | series=DHHS publication | issue=v. 3 | year=2002 | url=https://books.google.com/books?id=i4Xhbcw-vK0C&pg=PA210 | access-date=31 August 2024 | page=210}}</ref><ref name="Mosby2016">{{cite book | title=Mosby's Pocket Dictionary of Medicine, Nursing & Health Professions - E-Book: Mosby's Pocket Dictionary of Medicine, Nursing & Health Professions - E-Book | publisher=Elsevier Health Sciences | year=2016 | isbn=978-0-323-41427-2 | url=https://books.google.com/books?id=sH-JDAAAQBAJ&pg=PA810 | access-date=31 August 2024 | page=810}}</ref> Kombinasi teofilin, efedrin, dan barbiturat kemudian dihapuskan demi kombinasi teofilin dan efedrin saja.<ref name="Head2022" /><ref name="Mansfield1991">{{cite journal | vauthors = Mansfield PR | title = Classifying improvements to drug marketing and justifications for claims of efficacy | journal = The International Journal of Risk & Safety in Medicine | volume = 2 | issue = 4 | pages = 171–184 | date = 1991 | pmid = 23511913 | doi = 10.3233/JRS-1991-2401 | quote = Dr Lathem, Sterling's Vice President for Scientific Affairs replied to MaLAM that "Franol is approved for marketing in the United Kingdom in a formulation containing theophylline and ephedrine. We have initiated a re-formulation worldwide to make all Franol formulations consistent with those of the U.K.". Weinberger and Bronsky (1974) compared theophylline and ephedrine separately and combined. They concluded that "the inclusion of ephedrine resulted in no further benefit but did appear to increase the frequency of adverse effects" [26]. }}</ref> Kombinasi dosis tetap teofilin dan efedrin ditinggalkan setelah tahun 1970-an karena tidak memungkinkan titrasi dosis dalam terapi asma akibat toksisitas efedrin.<ref name="AkazawaStempel2006">{{cite journal | vauthors = Akazawa M, Stempel DA | title = Single-inhaler combination therapy for asthma: a review of cost effectiveness | journal = PharmacoEconomics | volume = 24 | issue = 10 | pages = 971–988 | date = 2006 | pmid = 17002480 | doi = 10.2165/00019053-200624100-00005 | quote = The concept of using a single therapy and maximising the dose of ICS might have been driven by the desire to avoid fixed combinations. These were commonly used in the US during the 1970s with products such as Tedral®1 and Marax® that combined theophylline and ephedrine with a sedative. The earlier fixed combinations did not allow for significant dose titration, due to the toxicity of ephedrine, and thus the concept of fixed dosing combinations for asthma was relegated to an ‘unacceptable’ status. }}</ref>
Kombinasi teofilin, efedrin, dan fenobarbital (nama merek Tedral antara lain) juga telah banyak digunakan untuk mengobati asma.[12][13][14][15] Banyak kombinasi tersebut telah dipasarkan dengan berbagai nama merek.[15] Teofilin juga telah dipasarkan dalam kombinasi dengan simpatomimetik seperti efedrin lainnya seperti rasefedrin dan pseudoefedrin dan dengan barbiturat lainnya seperti amobarbital dan butabarbital, di antara obat-obatan lainnya.[15] Kombinasi teofilin, efedrin, dan hidroksizin telah dipasarkan dengan nama merek Marax antara lain juga.[16][17][18] Kombinasi teofilin, efedrin, dan barbiturat kemudian dihapuskan demi kombinasi teofilin dan efedrin saja (misalnya, nama merek Franol).[2][1] Kombinasi dosis tetap teofilin dan efedrin ditinggalkan setelah tahun 1970-an karena tidak memungkinkan titrasi dosis dalam terapi asma akibat toksisitas efedrin.[19]
 
Efek teofilin/efedrin sebagai [[zat ergogenik|obat peningkat performa]] dalam [[latihan fisik]] dan [[olahraga]] telah dipelajari.<ref name="Kennedy2021">{{cite journal | vauthors = Kennedy M | title = Effects of theophylline and theobromine on exercise performance and implications for competition sport: A systematic review | journal = Drug Testing and Analysis | volume = 13 | issue = 1 | pages = 36–43 | date = January 2021 | pmid = 33188564 | doi = 10.1002/dta.2970 }}</ref><ref name="SidneyLefcoe1978">{{cite journal | vauthors = Sidney KH, Lefcoe NM | title = Effects of anti-asthmatic medication (ephedrine plus theophylline) upon the physical performance and work capacity of healthy track athletes | date = 1978 | journal = Can J Appl Sport Sci | volume = 3 | pages = 93–97 | url = https://scholar.google.com/scholar?cluster=707479795512859830}}</ref> Penggunaan kombinasi teofilin/efedrin telah menyebabkan diskualifikasi atlet elit karena efedrin dilarang dalam olahraga kompetitif.<ref name="HeleniusHaahtela2000">{{cite journal | vauthors = Helenius I, Haahtela T | title = Allergy and asthma in elite summer sport athletes | journal = The Journal of Allergy and Clinical Immunology | volume = 106 | issue = 3 | pages = 444–452 | date = September 2000 | pmid = 10984362 | doi = 10.1067/mai.2000.107749 | quote = Dokter tim mulai tertarik pada asma pada atlet elit setelah Olimpiade 1972 di Munich. Pemenang lomba renang gaya bebas putra 400 m didiskualifikasi karena sejumlah besar obat terlarang, termasuk efedrin yang ditemukan dalam sampel urinalisisnya setelah lomba. Perenang tersebut telah menggunakan kombinasi teofilin dan efedrin untuk mengobati asmanya. Sejak saat itu, Komite Olimpiade AS dan Australia telah memberikan penekanan khusus pada diagnosis dan pengobatan asma yang akurat pada tim Olimpiade mereka.1,2 }}</ref>
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[[Kategori:Simpatomimetik]]
[[Kategori:Xantina]]
[[Kategori:Hidroksiamfetamin beta]]
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