Side Effects of aminophylline: A Synthesis of Findings from 30 Studies

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Original Abstract of the Article

Main Research Findings

Aminophylline, a commonly used bronchodilator, has been found to have various side effects, particularly in relation to the cardiovascular system. 4 showed that aminophylline increased heart rate and contractility in human pluripotent stem cell-derived cardiomyocytes, suggesting an arrhythmogenic potential. While aminophylline has been investigated as a potential cancer treatment, it was found to be less effective than theophylline and exhibited high cytotoxicity at higher doses. 25 Additionally, aminophylline may cause changes in blood pressure, heart rate, and heart rate variability in newborns, particularly in cases of meconium aspiration syndrome (MAS). 1

Reasons for Side Effects

The side effects of aminophylline arise from its mechanism of action. Aminophylline inhibits the breakdown of intracellular cyclic AMP (cAMP), leading to increased cAMP levels. This elevation in cAMP can affect various cellular activities, potentially contributing to increased heart rate and blood pressure as well as arrhythmias. 4 Aminophylline also blocks adenosine receptors, which are involved in vasodilation. This blockade can lead to vasoconstriction and subsequently, higher blood pressure. 17

Common Side Effects

Cardiovascular

Aminophylline can lead to increased heart rate, blood pressure, and arrhythmias. 4 In newborns, aminophylline can impact blood pressure, heart rate, and heart rate variability. 1

Gastrointestinal

Aminophylline may cause gastrointestinal side effects such as stomach pain, nausea, vomiting, and diarrhea. 26

Nervous System

Aminophylline can lead to neurological side effects including headache, dizziness, tremors, anxiety, and insomnia. 19

Respiratory

While aminophylline is primarily used for asthma treatment, it can rarely cause difficulty breathing. 21

Countermeasures for Side Effects

Cardiovascular

Close monitoring of blood pressure, heart rate, and electrocardiogram is essential during aminophylline administration. Caution is advised for individuals with pre-existing cardiovascular conditions, the elderly, and newborns. 4 1

Gastrointestinal

Taking aminophylline after meals may help minimize stomach irritation. 26

Nervous System

Patients should be advised to avoid driving or operating machinery while taking aminophylline. 19

Comparison between Studies

Commonalities

Multiple studies have demonstrated the potential of aminophylline to affect the cardiovascular system, with findings including increased heart rate, blood pressure, and arrhythmias. 4 1

Differences

The manifestation of aminophylline's side effects can vary based on factors such as dosage, administration method, and individual patient characteristics. It's crucial to acknowledge that the results from different studies might have been obtained under distinct conditions.

Notes on Applying to Real Life

While aminophylline is a valuable bronchodilator, it's important to be aware of the potential for cardiovascular side effects. Individuals with heart conditions, the elderly, and newborns should exercise particular caution. Always follow your doctor's instructions when taking aminophylline. If you suspect any side effects, seek immediate medical attention. 4 1

Limitations of Current Research

The available research on the side effects of aminophylline is still limited. More studies are needed, particularly regarding long-term side effects. Furthermore, side effect profiles can vary significantly depending on individual patient characteristics and genetic background.

Future Research Directions

Additional research is crucial to further understand the side effects of aminophylline. This includes investigations into long-term side effects and how individual factors, such as patient condition and genetics, influence the occurrence of side effects.

Conclusion

Aminophylline is an effective bronchodilator but carries the risk of cardiovascular side effects. Always adhere to your doctor's instructions when taking aminophylline. If you experience any suspected side effects, seek immediate medical advice.

Literature analysis of 30 papers
Positive Content
26
Neutral Content
2
Negative Content
2
Article Type
6
3
2
4
30
1.

Cardiovascular side effects of aminophylline in meconium-induced acute lung injury.

Author: MokraD, TonhajzerovaI, MokryJ, PetraskovaM, HutkoM, CalkovskaA

Treat MAS
Cardiovascular changes

Intravenous aminophylline, a PDE inhibitor, can cause acute cardiovascular changes in neonatal meconium aspiration syndrome, leading to increased blood pressure and heart rate.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

2.

[Relation of dose, serum concentration and side effects in intravenous aminophylline therapy].

Author: KatzG, KewitzG, VozehS, FollathF

Aminophylline efficacy
Aminophylline side effects

Aminophylline therapy for chronic obstructive bronchitis required monitoring of serum theophylline levels to avoid toxicity.

English AbstractA summary of a research paper/publication written in English for a wider audience.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : German

5.

The effect of preoperative aminophylline on the recovery profile after major pelvic-abdominal surgeries: a randomized controlled double-blinded study.

Author: KasimSamaa A, BahrMahmoud Hussein, AbdelkaderMohamed, RashwanDoaa Abu Elkassim

Recovery enhancement

Premedication with aminophylline enhanced the recovery profile after pelvic-abdominal surgeries under general anesthesia without cardiovascular complications.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

6.

Comparative efficacy and safety of caffeine citrate and aminophylline in treating apnea of prematurity: A systematic review and meta-analysis.

Author: MiaoYiqun, ZhouYun, ZhaoShuliang, LiuWenwen, WangAihua, ZhangYuanyuan, LiYanan, JiangHuimin

Depression management
PPD

This meta-analysis compared the efficacy and safety of caffeine citrate and aminophylline for apnea of prematurity. Both medications had similar therapeutic effectiveness on respiratory function, but caffeine was associated with fewer side effects, including tachycardia and feeding intolerance.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.
Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.

Language : English

8.

Aminophylline shortage and current recommendations for reversal of vasodilator stress: an ASNC information statement endorsed by SCMR.

Author: AbidovAiden, DilsizianVasken, DoukkyRami, DuvallW Lane, DykeChristopher, ElliottMichael D, HageFadi G, HenzlovaMilena J, JohnsonNils P, SchwartzRonald G, ThomasGregory S, EinsteinAndrew J

SISE reversal
aminophylline shortage

This information statement addresses pharmacologic reversal of serious or intolerable side effects (SISEs) from vasodilator stress, focusing on the need for alternative agents to aminophylline due to its recurring shortages. It provides recommendations on indications for reversal, timing of agents, SISE incidence, and alternative non-aminophylline based reversal protocols.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

9.

Aminophylline shortage and current recommendations for reversal of vasodilator stress: An ASNC information statement endorsed by SCMR.

Author: AbidovAiden, DilsizianVasken, DoukkyRami, DuvallW Lane, DykeChristopher, ElliottMichael D, HageFadi G, HenzlovaMilena J, JohnsonNils P, SchwartzRonald G, ThomasGregory S, EinsteinAndrew J

SISE reversal
aminophylline shortage

This information statement addresses pharmacologic reversal of serious or intolerable side effects (SISEs) from vasodilator stress, focusing on the need for alternative agents to aminophylline due to its recurring shortages. It provides recommendations on indications for reversal, timing of agents, SISE incidence, and alternative non-aminophylline based reversal protocols.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

10.

Aminophylline and caffeine for reversal of adverse symptoms associated with regadenoson SPECT MPI.

Author: DoranJesse A, SajjadWaseem, SchneiderMarabel D, GuptaRohit, MackinMaria L, SchwartzRonald G

Rapid reversal

Intravenous aminophylline and IV caffeine provide rapid, safe reversal of regadenoson-induced adverse effects during SPECT MPI. Oral caffeine appeared similarly effective for complete reversal but not for the combined complete and predominant reversal.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Retracted PublicationCases where a publication has been formally withdrawn due to the discovery of serious errors or misconduct.

Language : English

11.

A prospective assessment of the effect of aminophylline therapy on urine output and inflammation in critically ill children.

Author: TamburroRobert F, ThomasNeal J, CenevivaGary D, DettorreMichael D, BrummelGretchen L, LuckingSteven E

Anti-inflammatory effect
Diuretic effect

A prospective study assessed the hypothesis that aminophylline increases urine output and decreases inflammation in critically ill children.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

12.

Experience of low-dose aminophylline use to relieve minor adverse effects of dipyridamole in patients undergoing stress myocardial perfusion imaging.

Author: LinLi-Fan, ChengCheng-Yi, HouCheng-Han, KuChih-Hung, TsengNeng-Chuan, ShenDaniel H Y

Relief of mild AEs

Low-dose (≤50mg) aminophylline is sufficient to relieve mild dipyridamole-related AEs during stress MPI.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

13.

Comparison of the recovery and respiratory effects of aminophylline and doxapram following total intravenous anesthesia with propofol and remifentanil.

Author: KimDae Woo, JooJin Deok, InJang Hyeok, JeonYeon Su, JungHong Soo, JeonKyeong Bae, ParkJae Sik, ChoiJin Woo

Improved early recovery
Shortened time to ventilation
None

Aminophylline 3 mg/kg or doxapram 1 mg/kg shortened the time to spontaneous ventilation and improved early recovery from TIVA without appreciable side effects. Aminophylline showed comparable arousal and respiratory effects to doxapram.

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

14.

The safety and tolerability of regadenoson in patients with end-stage renal disease: the first prospective evaluation.

Author: DoukkyRami, RangelMaria Octavia, WassoufMarwan, DickRizcallah, AlqaidAmmar, Morales DemoriRaysa

Diarrhea
Dizziness

Regadenoson (REG) stress testing was safe and well-tolerated in patients with end-stage renal disease (ESRD).

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.

Language : English

16.

Safety and feasibility of regadenoson use for suboptimal heart rate response during symptom-limited standard Bruce exercise stress test.

Author: PartingtonSara L, LankaViswanatha, HainerJon, BlanksteinRon, SkaliHicham, FormanDaniel E, Di CarliMarcelo F, DorbalaSharmila

Reduced side effects
Safe and feasible

Injecting regadenoson at peak exercise stress test (ETT) for submaximal heart rate response was safe, feasible, and well-tolerated. It provided a diagnostic myocardial perfusion imaging (MPI) with reporting of functional capacity and exercise information.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.

Language : English

17.

Additive diuretic response of concurrent aminophylline and furosemide in children: a case series and a brief literature review.

Author: da SilvaPaulo Sérgio Lucas, de AguiarVânia Euzébio, FonsecaMarcelo Cunio Machado

Increased urine output

Aminophylline, a drug used for diuresis, was successfully used as an adjunct diuretic in 4 critically ill children unresponsive to furosemide.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

18.

Safety of regadenoson as a pharmacologic stress agent for myocardial perfusion imaging in chronic kidney disease patients not on hemodialysis.

Author: PalaniGurunanthan, HusainZehra, SalinasRafael Cabrera, KarthikeyanVanji, KarthikeyanAarthee S, AnanthasubramaniamKarthik

REG-SPECT safety
Blunted heart rate

REG-SPECT can be safely performed in CKD non-dialysis patients with excellent tolerability, minimal side effects, and favorable hemodynamic responses compared to the control group.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

19.

Bemegride lengthens seizure duration during electric convulsive therapy in a schizophrenic patient with increased seizure threshold.

Author: KatagaiHiroshi, Yasui-FurukoriNorio, KikuchiAtsuhiro, KanekoSunao

Improved seizure quality
Hypertension
Tachycardia

This case report describes the use of bemegride as an alternative measure to improve seizure quality in a patient with schizophrenia undergoing electroconvulsive therapy.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

20.

Aminophylline reversal of prolonged postoperative sedation induced by propofol.

Author: SakuraiSatoru, FukunagaAtsuo, FukudaKenichi, KasaharaMasataka, IchinoheTatsuya, KanekoYuzuru

Propofol reversal

Aminophylline, a drug used to treat breathing problems, can reverse prolonged sedation caused by propofol, a common anesthetic. This was shown in case reports where aminophylline was used to wake up patients who had not fully recovered from propofol anesthesia. Aminophylline was found to be effective in reversing the sedative effects of propofol without any side effects or delayed re-sedation.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

21.

Side effect profile and tolerability of adenosine myocardial perfusion scintigraphy in patients with mild asthma or chronic obstructive pulmonary disease.

Author: ReyesEliana, LoongChee Y, WechalekarKshama, LatusKatherine, AnagnostopoulosConstantinos, UnderwoodS Richard

Myocardial perfusion scintigraphy
Bronchoconstriction

Adenosine stress testing was found to be tolerable in patients with mild asthma or COPD undergoing myocardial perfusion scintigraphy.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

22.

Adverse drug reactions and therapeutic errors in older adults: a hazard factor analysis of poison center data.

Author: CobaughDaniel J, KrenzelokEdward P

Medication hazards

An analysis of adverse drug reactions (ADRs) and therapeutic errors involving older adults and reported to poison control centers from 1993 through 2002 revealed overall rates of major effects and death of 7.5% and 1.6% in the ADR and therapeutic error groups, respectively. Antineoplastics, aminophylline or theophylline, cardiac glycosides, heparin, morphine, and warfarin were implicated in more than 50 cases and associated with hazard factors of > or =2.0 for both exposure groups.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

23.

Oral xanthines as maintenance treatment for asthma in children.

Author: SeddonP, BaraA, DucharmeF M, LassersonT J

Improved lung function
Reduced rescue medication use
Increased adverse events

Xanthines as first-line preventers alleviate symptoms and reduce the requirement for rescue medication in children with mild to moderate asthma.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Meta-AnalysisA statistical technique that integrates the results of multiple studies to draw more general conclusions about a particular issue.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.
Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.

Language : English

24.

Induction of apoptosis in non-small lung carcinoma cell line (H1299) by combination of anti-asthma drugs with gemcitabine and cisplatin.

Author: MerimskyO, HirshL, DantesA, Land-BrachaA, SuhB S, AmsterdamA

Increased apoptosis
Reduced chemotherapy dose

Theophylline and aminophylline, anti-asthma drugs, were investigated for their potential to enhance the effectiveness of gemcitabine and cisplatin, chemotherapy drugs. Theophylline significantly increased apoptosis in lung cancer cells when combined with gemcitabine or cisplatin.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

25.

Phosphodiesterase inhibitors as anti-cancer drugs.

Author: HirshLiron, DantesAda, SuhByong-Sun, YoshidaYoshio, HosokawaKumiko, TajimaKimihisa, KotsujiFumikazu, MerimskyOfer, AmsterdamAbraham

Cancer cell death
Reduced chemotherapy dosage
Cytotoxicity

This study examined the effectiveness of theophylline and aminophylline, phosphodiesterase blockers that can elevate intracellular cAMP, in inducing cell death in various cancer cell lines. The results showed that theophylline synergized with cisplatin and gemcitabine to induce apoptosis, allowing for a reduction in the effective doses of these chemotherapy drugs.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

26.

Study on the effect of food on the absorption of theophylline.

Author: SuYih-Ming, ChengTien-Pao, WenCheng-Yu

This study investigates the impact of food, especially Chinese food, on the pharmacokinetics of Euphyllin Retard in Chinese subjects.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

28.

Dose response of intrathecal adenosine in experimental pain and allodynia.

Author: EisenachJames C, CurryRegina, HoodDavid D

Pain relief
Side effects

This study investigated the dose-response relationship of intrathecal adenosine in patients with experimental hypersensitivity. Two doses of intrathecal adenosine were administered, and the ability of aminophylline, an adenosine receptor antagonist, to reverse adenosine's effects was evaluated.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, U.S. Gov't, P.H.S.Research funding provided by the Public Health Service (PHS).

Language : English

29.

A randomized, controlled, double-blind trial comparing two loading doses of aminophylline.

Author: HochwaldChristine, KennedyKathleen, ChangJocelin, MoyaFernando

Faster theophylline level achievement

This study compared 8 mg/kg and 6 mg/kg loading doses of aminophylline in 61 preterm infants weighing <1500 g. The 8 mg/kg group achieved recommended serum theophylline levels (7-12 microg/ml) more frequently than the 6 mg/kg group (39% vs 3%, p=0.002). There were no increases in side effects with the higher loading dose. The use of an 8 mg/kg loading dose appears to be a better and safe way to quickly achieve serum theophylline levels within the recommended range.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

30.

Comparison of aminophylline and insulin-dextrose infusions in acute therapy of hyperkalemia in end-stage renal disease patients.

Author: MahajanS K, ManglaM, KishoreK

Reduced potassium levels
Hypoglycemia

Aminophylline is an effective treatment for acute hyperkalemia in patients with end-stage renal disease (ESRD). However, insulin-dextrose infusion is more effective in lowering potassium levels. Both treatments were well-tolerated, with one episode of hypoglycemia observed in the insulin-dextrose group.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

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