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Aminophylline

Aminophylline is known as a potent bronchodilator medicine. This means that it opens the airways of the lungs by relaxing the smooth muscles. Because of this effect, aminophylline is prescribed for the treatment of wheezing, breathing difficulties, asthma, emphysema, chronic bronchitis, acute bronchospasm, and other respiratory disorders.

Overall Health Benefits of Aminophylline

  • Promotes Weight Loss [1-5]
  • Improves Cognitive Function [6-8]
  • Improves Sleep Quality [9-11]
  • Improves Cardiovascular Health [12-20]
  • Treats Lung Diseases/Injuries [21-39]
  • Improves Kidney Function [40-50]

How Aminophylline Works

Aminophylline achieves its therapeutic effect through the following mechanisms:

  • It relaxes the smooth muscles of the lungs to allow more air in.
  • It reduces inflammation by decreasing the sensitivity of the lungs to allergens.
  • It draws more air into the lungs by increasing the contractions of the diaphragm.

Proven Benefits of Aminophylline

Promotes Weight Loss

A good deal of evidence also suggests that aminophylline can improve body composition by reducing body fat percentage and promoting lean muscle mass:

  • In overweight men and women, application of 0.5% aminophylline cream to the waist twice a day was associated with significant reduction in waist circumference. [1]
  • In participants with fat deposits on their thighs, application of aminophylline lotion significantly reduced thigh circumference, thigh skinfold thickness, and thigh fat mass. [2]
  • Twelve weeks of 0.5% aminophylline cream administration significantly decreased waist-to-hip ratios in overweight female participants compared to male participants. [3]
  • A study found that aminophylline promotes fat loss by inducing breakdown of fat cells. [4]
  • In women with lower body fat distribution, application of aminophylline cream significantly reduced thigh fat. [5]

Improves Cognitive Function

Studies also support that aminophylline has cognitive-boosting properties:

  • Administration of escalating doses of aminophylline in patients who received sevoflurane anesthesia accelerated postoperative cognitive recovery. [6]
  • In school-aged patients, aminophylline administration led to greater improvement on all tests of memory and concentration. [7]
  • In patients with brain damage, aminophylline administration improved cognitive function by increasing oxygen levels within the brain. [8]

Improves Sleep Quality

Aminophylline administration can also help treat sleeping difficulties associated with various medical conditions:

  • In healthy male volunteers, aminophylline administration normalized high-altitude sleep-disordered breathing. [9]
  • In patients with obstructive sleep apnea syndrome, aminophylline improved impaired breathing and increased NREM (non-rapid eye movement) sleep or dreamless sleep. [10]
  • In patients with sleeping difficulties related to acute mountain sickness, aminophylline administration improved sleep efficiency without any adverse effects. [11]

Improves Cardiovascular Health

There’s also increasing evidence showing that aminophylline can help improve heart health:

  • A study found that aminophylline has the ability to restore normal heart rhythm, thus reducing one’s risk for heart failure and other fatal heart conditions. [12]
  • In COPD patients, oral and intravenous administration of aminophylline enhanced both right and left heart systolic pump function. [13-14]
  • In human subjects, aminophylline administration increased heart rate and cardiac output via stimulation of the sympathetic nervous system. [15-16]
  • In COPD patients, aminophylline administration improved global cardiac function and reduced dyspnea. [17-18]
  • In animal models, aminophylline improved left ventricular contractility and heart rate variability (interval between heartbeats). [19-20]

Treats Lung Diseases/Injuries

Aminophylline is often prescribed for a multitude of lung conditions. There’s robust evidence supporting the benefits of this drug on pulmonary health:

  • In adults hospitalized for acute asthma, treatment with aminophylline was associated with fewer nebulizations of albuterol and lower rate of exacerbations. [21-22]
  • In patients with acute severe asthma, aminophylline infusions improved lung function and symptoms. [23]
  • In patients with respiratory fatigue, aminophylline administration reduced the risk of intubation. [24]
  • In patients with partially reversible severe airway obstruction, intravenous injections of aminophylline (250 mg) was associated with consistent improvement in the mean forced expiratory volume, a measure of how much air a person can exhale during a forced breath. [25]
  • In patients with acute exacerbation of asthma or chronic obstructive pulmonary disease, aminophylline infusion decreased hospital admissions. [26]
  • In patients with chronic obstructive pulmonary disease (COPD), aminophylline administration improved symptoms by reducing the levels of inflammatory markers. [27]
  • In patients with COPD, oral administration of aminophylline (400 mg) increased mean forced expiratory volume and forced vital capacity. [28-29]
  • In patients with COPD, low dose aminophylline increased the efficacy of inhaled corticosteroids by reducing the incidence of exacerbations. [30-31]
  • In patients undergoing valve replacement, aminophylline administration had anti-inflammatory effect and improved pulmonary oxygenation. [32]
  • Prolonged use of maintenance aminophylline therapy in COPD patients increased diaphragmatic contractility and endurance and improved several aspects of mucociliary function (defense mechanism of the lung). [33]
  • Administration of long-acting 225-mg aminophylline compounds twice daily for 8 weeks improved peak expiratory flow rate in younger COPD patients and relieved symptoms of chest tightness in older COPD patients. [34]
  • Aminophylline administration in COPD patients enhanced the anti-inflammatory effect of corticosteroids. [35]
  • In patients with chronic bronchitis and moderate to severe chronic obstruction to airflow, aminophylline administration at 800 mg daily led to an improvement in peripheral ventilation. [36]
  • In normal young adults, aminophylline prevented alterations in breathing pattern. [37]
  • In patients with mild asthma, low-dose aminophylline led to a significant reduction in mean sputum eosinophils (a measure of allergic reaction). [38]
  • In patients with atopic asthma, aminophylline administration at 200 mg every 12 hours reduced airway inflammatory response to allergen inhalation. [39]

Improves Kidney Function

Numerous studies also support the beneficial effects of aminophylline on kidney function and related diseases:

  • In patients with acute kidney injury, aminophylline therapy significantly improved renal excretory function as evidenced by increased urine output. [40]
  • In neonates and children, a single dose of aminophylline prevented acute kidney injury and severe renal dysfunction. [41]
  • In patients with renal colic, a type of pain associated with kidney stones, administration of 375 mg of aminophylline reduced pain by 24% to 39%. [42]
  • Aminophylline administration also reduced the prevalence of acute kidney injury after cardiac surgery in pediatric patients. [43]
  • In patients with acute renal failure, aminophylline administration was associated with an improvement in renal function indices. [44]
  • In premature infants, aminophylline improved kidney function by enhancing urinary calcium and uric acid excretion. [45]
  • Intravenous aminophylline administration in human subjects was associated with a 52% reduction in the risk of contrast-induced acute kidney injury. [46-47]
  • In intensive care unit patients with acute kidney injury, aminophylline infusion at 5 mg/kg increased urine output. [48]
  • In patients admitted to a general intensive care unit following major surgery, aminophylline administration increased blood flow to the kidneys and improved glomerular filtration rate (filtering ability of the kidneys). [49]
  • In patients undergoing chemotherapy, aminophylline administration prevented the deterioration of glomerular filtration rate. [50]

References:

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  2. Escalante G, Bryan P, Rodriguez J. Effects of a topical lotion containing aminophylline, caffeine, yohimbe, l-carnitine, and gotu kola on thigh circumference, skinfold thickness, and fat mass in sedentary females. J Cosmet Dermatol. 2018.
  3. Lundberg GD. Fat reduction by topical waist applications may actually work. Medscape J Med. 2008;10(2):43. Published 2008 Feb 21.
  4. Available from https://academic.oup.com/asj/article/17/5/304/177651.
  5. Available from https://journals.lww.com/plasreconsurg/fulltext/2013/09000/Thigh_Girth_Loss_in_Women_with_Lower_Body_Fat.61.aspx.
  6. El tahan MR. Effects of aminophylline on cognitive recovery after sevoflurane anesthesia. J Anesth. 2011;25(5):648-56.
  7. Furukawa CT, Duhamel TR, Weimer L, Shapiro GG, Pierson WE, Bierman CW. Cognitive and behavioral findings in children taking theophylline. J Allergy Clin Immunol. 1988;81(1):83-8.
  8. Mitrouska I, Kondili E, Prinianakis G, Siafakas N, Georgopoulos D. Effects of theophylline on ventilatory poststimulus potentiation in patients with brain damage. Am J Respir Crit Care Med. 2003;167(8):1124-30.
  9. Fischer R, Lang SM, Leitl M, Thiere M, Steiner U, Huber RM. Theophylline and acetazolamide reduce sleep-disordered breathing at high altitude. Eur Respir J. 2004;23(1):47-52.
  10. Espinoza H, Antic R, Thornton AT, Mcevoy RD. The effects of aminophylline on sleep and sleep-disordered breathing in patients with obstructive sleep apnea syndrome. Am Rev Respir Dis. 1987;136(1):80-4.
  11. Küpper TE, Strohl KP, Hoefer M, Gieseler U, Netzer CM, Netzer NC. Low-dose theophylline reduces symptoms of acute mountain sickness. J Travel Med. 2008;15(5):307-14.
  12. Rudusky BM. Aminophylline: exploring cardiovascular benefits versus medical malcontent. Angiology. 2005;56(3):295-304.
  13. Matthay RA. Favorable cardiovascular effects of theophylline in COPD. Chest. 1987;92(1 Suppl):22S-26S.
  14. Matthay RA. Effects of theophylline on cardiovascular performance in chronic obstructive pulmonary disease. Chest. 1985;88(2 Suppl):112S-117S.
  15. Vestal RE, Eiriksson CE, Musser B, Ozaki LK, Halter JB. Effect of intravenous aminophylline on plasma levels of catecholamines and related cardiovascular and metabolic responses in man. Circulation. 1983;67(1):162-71.
  16. Walther FJ, Sims ME, Siassi B, Wu PY. Cardiac output changes secondary to theophylline therapy in preterm infants. J Pediatr. 1986;109(5):874-6.
  17. Matthay RA, Mahler DA. Theophylline improves global cardiac function and reduces dyspnea in chronic obstructive lung disease. J Allergy Clin Immunol. 1986;78(4 Pt 2):793-9.
  18. Dutt AK, De soyza ND, Au WY, Hargis JL, Tuck RL. The effect of aminophylline on cardiac rhythm in advanced chronic obstructive pulmonary disease: correlation with serum theophylline levels. Eur J Respir Dis. 1983;64(4):264-70.
  19. Rutherford JD, Vatner SF, Braunwald E. Effects and mechanism of action of aminophylline on cardiac function and regional blood flow distribution in conscious dogs. Circulation. 1981;63(2):378-87.
  20. Mokra D, Tonhajzerova I, Mokry J, Petraskova M, Hutko M, Calkovska A. Cardiovascular side effects of aminophylline in meconium-induced acute lung injury. Adv Exp Med Biol. 2013;756:341-7.
  21. Huang D, O’brien RG, Harman E, et al. Does aminophylline benefit adults admitted to the hospital for an acute exacerbation of asthma?. Ann Intern Med. 1993;119(12):1155-60.
  22. Mahemuti G, Zhang H, Li J, Tieliwaerdi N, Ren L. Efficacy and side effects of intravenous theophylline in acute asthma: a systematic review and meta-analysis. Drug Des Devel Ther. 2018;12:99-120.
  23. Neame M, Aragon O, Fernandes RM, Sinha I. Salbutamol or aminophylline for acute severe asthma: how to choose which one, when and why?. Arch Dis Child Educ Pract Ed. 2015;100(4):215-22.
  24. Nuhoglu Y, Nuhoglu C. Aminophylline for treating asthma and chronic obstructive pulmonary disease. Expert Rev Respir Med. 2008;2(3):305-13.
  25. Freitag A. Aminophylline injection and theophylline tablets: Acute response in partially reversible chronic airway obstruction. Med J Aust. 1976;1(14):478-9.
  26. Wrenn K, Slovis CM, Murphy F, Greenberg RS. Aminophylline therapy for acute bronchospastic disease in the emergency room. Ann Intern Med. 1991;115(4):241-7.
  27. Rabe KF, Hiemstra PS. Theophylline for chronic obstructive pulmonary disease?.Time to move on. Am J Respir Crit Care Med. 2010;182(7):868-9.
  28. Shim CS, Williams MH. Bronchodilator response to oral aminophylline and terbutaline versus aerosol albuterol in patients with chronic obstructive pulmonary disease. Am J Med.
    1983;75(4):697-701.
  29. Ram FS, Jardin JR, Atallah A, et al. Efficacy of theophylline in people with stable chronic obstructive pulmonary disease: a systematic review and meta-analysis. Respir Med. 2005;99(2):135-44.
  30. Devereux G, Cotton S, Barnes P, et al. Use of low-dose oral theophylline as an adjunct to inhaled corticosteroids in preventing exacerbations of chronic obstructive pulmonary disease: study protocol for a randomised controlled trial. Trials. 2015;16:267. Published 2015 Jun 10. doi:10.1186/s13063-015-0782-2.
  31. Devereux G, Cotton S, Fielding S, et al. Effect of Theophylline as Adjunct to Inhaled Corticosteroids on Exacerbations in Patients With COPD: A Randomized Clinical Trial. JAMA. 2018;320(15):1548-1559.
  32. Luo WJ, Ling X, Huang RM. Effects of aminophylline on cytokines and pulmonary function in patients undergoing valve replacement. Eur J Cardiothorac Surg. 2004;25(5):766-71.
    Available from https://www.jacionline.org/article/0091-6749(86)90064-3/fulltext.
  33. Chen CY, Yang KY, Lee YC, Perng PP. Effect of oral aminophylline on pulmonary function improvement and tolerability in different age groups of COPD patients. Chest. 2005;128(4):2088-92.
  34. Barnes PJ. Theophylline in chronic obstructive pulmonary disease: new horizons. Proceedings of the American Thoracic Society. 2005; 2(4):334-9; discussion 340-1.
  35. Chrystyn H, Mulley BA, Peake MD. Dose response relation to oral theophylline in severe chronic obstructive airways disease. BMJ. 1988;297(6662):1506-10.
  36. Georgopoulos D, Holtby SG, Berezanski D, Anthonisen NR. Aminophylline effects on ventilatory response to hypoxia and hyperoxia in normal adults. J Appl Physiol. 1989;67(3):1150-6.
  37. Lim S, Tomita K, Caramori G, et al. Low-dose theophylline reduces eosinophilic inflammation but not exhaled nitric oxide in mild asthma. Am J Respir Crit Care Med. 2001;164(2):273-6.
  38. Sullivan P, Bekir S, Jaffar Z, Page C, Jeffery P, Costello J. Anti-inflammatory effects of low-dose oral theophylline in atopic asthma. Lancet. 1994;343(8904):1006-8.
  39. Axelrod DM, Anglemyer AT, Sherman-levine SF, et al. Initial experience using aminophylline to improve renal dysfunction in the pediatric cardiovascular ICU. Pediatr Crit Care Med. 2014;15(1):21-7.
  40. Bhatt GC, Gogia P, Bitzan M, Das RR. Theophylline and aminophylline for prevention of acute kidney injury in neonates and children: a systematic review. Arch Dis Child. 2019.
  41. Djaladat H, Tajik P, Fard SA, Alehashemi S. The effect of aminophylline on renal colic: a randomized double blind controlled trial. South Med J. 2007;100(11):1081-4.
  42. Mcmahon K, Zappitelli M. Aminophylline for Acute Kidney Injury After Pediatric Cardiac Surgery: Finally Entering the Next Phase in Child Acute Kidney Injury Research. Pediatr Crit Care Med. 2016;17(2):170-1.
  43. Lynch BA, Gal P, Ransom JL, et al. Low-dose aminophylline for the treatment of neonatal non-oliguric renal failure-case series and review of the literature. J Pediatr Pharmacol Ther. 2008;13(2):80–87. doi:10.5863/1551-6776-13.2.80.
  44. Mazkereth R, Laufer J, Jordan S, Pomerance JJ, Boichis H, Reichman B. Effects of theophylline on renal function in premature infants. Am J Perinatol. 1997;14(1):45-9.
  45. Mccullough PA, Larsen T, Brown JR. Theophylline or aminophylline for the prevention of contrast-induced acute kidney injury. Am J Kidney Dis. 2012;60(3):338-9.
  46. Ix JH, Mcculloch CE, Chertow GM. Theophylline for the prevention of radiocontrast nephropathy: a meta-analysis. Nephrol Dial Transplant. 2004;19(11):2747-53.
    Available from https://clinicaltrials.gov/ct2/show/NCT02983422.
  47. Parker MR, Willatts SM. A pilot study to investigate the effects of an infusion of aminophylline on renal function following major abdominal surgery. Anaesthesia. 2001;56(7):670-5.
  48. Benoehr P, Krueth P, Bokemeyer C, Grenz A, Osswald H, Hartmann JT. Nephroprotection by theophylline in patients with cisplatin chemotherapy: a randomized, single-blinded, placebo-controlled trial. J Am Soc Nephrol. 2005;16(2):452-8.
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