Side Effects of theophylline: A Synthesis of Findings from 19 Studies

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Original Abstract of the Article

Main Research Findings

Theophylline, a bronchodilator, has been used to treat asthma and chronic obstructive pulmonary disease (COPD). However, it carries a risk of side effects and its effectiveness may be inferior to other drugs. Several side effects have been reported in patients who received theophylline. The 6 study found that patients who read the package insert describing the side effects of theophylline experienced significantly more side effects than those who did not. The rate of patients who stopped treatment due to complaints of side effects was also significantly higher in the group that read the package insert. The 10 study showed that an increase in theophylline plasma concentration did not significantly improve lung function. In addition, theophylline can affect the gastrointestinal, nervous, and cardiovascular systems, potentially causing serious side effects. The 8 study found that several patients discontinued treatment due to theophylline side effects. The 17 study found that patients with COVID-19 who received remdesivir experienced significant bradycardia and QTc prolongation. The 19 study suggests that theophylline may induce seizures. The 16 study found that caffeine was more effective and had fewer side effects than aminophylline/theophylline in treating apnea of prematurity. The 14 study aims to develop a clinical care bundle incorporating caffeine citrate to prevent and manage AOP in tertiary healthcare facilities in Kenya, as caffeine has been found to be more effective and have fewer side effects than aminophylline/theophylline in the treatment of apnea of prematurity. The study reported that theophylline can cause side effects such as nausea, vomiting, headache, dizziness, tremor, insomnia, etc. The 1 study suggested that theophylline may cause behavioral changes in children. The 11 study found that long-term theophylline users with vague gastrointestinal symptoms or cardiac symptoms should be suspected of theophylline toxicity. The 13 study found that caffeine can improve exercise performance, but can cause side effects such as insomnia and anxiety. The 9 study found that side effects can occur even when theophylline plasma concentrations are within the therapeutic range. The 15 study found that elderly patients are more susceptible to theophylline side effects. The 5 study found that there are some points to note when using theophylline for acute asthma, such as age and concomitant medications. The 3 study found that theophylline has more psychological side effects than beclomethasone. The 18 study suggests that theophylline may be effective in preventing syncope. The 7 study found that bamifylline has fewer side effects than theophylline. The 4 study found that theophylline may slow gastric emptying in very low birth weight neonates.

Reasons for Side Effects

The reason for theophylline side effects lies in its pharmacological action. Theophylline acts on various organs including the central nervous system, cardiovascular system, and digestive system, resulting in various side effects. Theophylline acts as an adenosine receptor antagonist, inhibiting the vasodilatory and bronchoconstrictive effects of adenosine. However, adenosine plays an important role in heart function and digestive system function, so theophylline side effects such as increased heart rate, digestive disorders, and vomiting can occur.

Common Side Effects

Gastrointestinal

Theophylline can affect the gastrointestinal system, causing side effects such as nausea, vomiting, abdominal pain, and loss of appetite. The 11 study reported gastrointestinal symptoms from long-term theophylline use. The study also reported gastrointestinal side effects. The 4 study showed that theophylline may slow gastric emptying in preterm infants, potentially causing abdominal distention and vomiting.

Nervous System

Theophylline can affect the nervous system, causing side effects such as headache, dizziness, tremor, insomnia, anxiety, and nervousness. The study reported side effects related to the nervous system. The 1 study suggested that theophylline may cause behavioral changes in children. The 19 study suggests that theophylline may induce seizures. The 13 study found that caffeine can improve exercise performance, but can cause side effects such as insomnia and anxiety.

Cardiovascular

Theophylline can affect the cardiovascular system, causing side effects such as increased heart rate, palpitations, and increased blood pressure. The 17 study found that bradycardia and QTc prolongation were observed in patients with COVID-19 after remdesivir administration. The 18 study suggests that theophylline may be effective in preventing syncope.

Others

Other side effects of theophylline include rash, itching, and fever. The 6 study found that patients who saw the package insert describing the side effects of theophylline had significantly more side effects than those who did not. The proportion of patients who stopped treatment due to complaints of side effects was also significantly higher in the group that saw the package insert. The 15 study found that elderly patients are more susceptible to theophylline side effects.

Side Effect Countermeasures

Gastrointestinal Side Effects

To reduce gastrointestinal side effects, it is recommended that theophylline be taken with meals or in small doses. Reducing the dose of theophylline can also be effective. The 11 study found that patients who experienced gastrointestinal symptoms had their theophylline levels measured and received appropriate treatment.

Nervous System Side Effects

To reduce nervous system side effects, it is recommended that theophylline dosage be reduced. In some cases, it may be necessary to stop taking theophylline. The 1 study found that if behavioral changes are observed in children, it may be necessary to consider discontinuing theophylline use.

Cardiovascular Side Effects

To reduce cardiovascular side effects, it is recommended that theophylline dosage be reduced. In some cases, it may be necessary to stop taking theophylline. The 17 study found that patients with bradycardia stopped taking theophylline.

Other Side Effects

If you experience side effects such as rash or fever, consult a doctor. It may be necessary to reduce the dose of theophylline or stop taking it altogether.

Comparison between Studies

Commonalities

Multiple studies have shown that theophylline can affect the gastrointestinal, nervous, and cardiovascular systems, causing a variety of side effects. It has also been shown that theophylline side effects vary from patient to patient.

Differences

The incidence and severity of theophylline side effects vary from study to study. This may be due to factors such as the study population, theophylline dosage, and concomitant medications. Theophylline side effects are individual-specific and caution is required.

Precautions for Real-life Application

Theophylline is an effective bronchodilator, but it has the risk of side effects. Always follow your doctor's instructions when taking theophylline. If you experience any unusual symptoms while taking theophylline, consult your doctor immediately.

Limitations of Current Research

Research on theophylline side effects is still insufficient. In particular, more research is needed on the long-term effects of theophylline and the side effects of theophylline in specific patient groups.

Future Research Directions

Further research on theophylline side effects is needed. In particular, more research is needed on the long-term effects of theophylline and the side effects of theophylline in specific patient groups. There is also a need to develop new ways to reduce theophylline side effects.

Conclusion

Theophylline is an effective bronchodilator, but it has the risk of side effects. Always follow your doctor's instructions when taking theophylline. If you experience any unusual symptoms while taking theophylline, consult your doctor immediately. Further research on theophylline side effects is needed. In particular, more research is needed on the long-term effects of theophylline and the side effects of theophylline in specific patient groups. There is also a need to develop new ways to reduce theophylline side effects.

Literature analysis of 19 papers
Positive Content
13
Neutral Content
2
Negative Content
4
Article Type
5
1
1
3
17
1.

Theophylline-induced behavior change in children. An objective evaluation of parents' perceptions.

Author: BenderB, MilgromH

Side effects

Parental beliefs about theophylline-induced behavioral side effects were not supported by their own observations.

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, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

2.

Effects of theophylline on behavior and learning in children with asthma.

Author: RappaportL, CoffmanH, GuareR, FentonT, DeGrawC, TwarogF

Improved memory
Shaking hands
Stomach ache

Theophylline had no significant effects on behavior, attention, memory, or fine motor function in children with asthma. However, parents and children reported more stomachaches and shaking hands when taking theophylline.

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, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

3.

Neuropsychological and behavioral changes in asthmatic children treated with beclomethasone dipropionate versus theophylline.

Author: BenderB G, IkléD N, DuHamelT, TinkelmanD

Psychological side effects

The relative psychological side effects of theophylline and beclomethasone in asthmatic children need further investigation.

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.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.

Language : English

4.

Theophylline and gastric emptying in very low birthweight neonates: a randomised controlled trial.

Author: GounarisA, KokoriP, VarchalamaL, KonstandinidiK, SkouroliakouM, AlexiouN, CostalosC

Delayed gastric emptying

Theophylline treatment delays gastric emptying in very low birthweight neonates, which should be considered when using the drug to treat apnea of prematurity.

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

5.

Efficacy and side effects of intravenous theophylline in acute asthma: a systematic review and meta-analysis.

Author: MahemutiGulixian, ZhangHui, LiJing, TieliwaerdiNueramina, RenLili

Asthma treatment

Theophylline is a long-standing asthma treatment, but its effectiveness and side effects in different patient groups need further investigation. This meta-analysis assesses theophylline's usefulness and side effects in acute 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

6.

Manufacturer's information insert and subjective theophylline side-effects.

Author: VescoD, ToumiM, FarajF, RazzoukH, OrehekJ

Side-effect awareness

The presence of a manufacturer's insert detailing side effects in theophylline packages may lead to increased reporting of side effects and decreased compliance to therapy in asthmatic patients.

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

7.

[Bamifylline in the therapy of asthmatic syndromes. Efficacy and side effects vs delayed-action theophylline anhydride].

Author: AlciatoP, CantoneP A, FicoD, GagliardiniR, PetrellaV

Bronchodilation
Symptom relief
Gastric intolerance

Slow-release theophylline anhydride and bamiphylline are equally effective in treating bronchial asthma and chronic obstructive bronchial pneumonia, with minimal side effects.

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
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 : Italian

8.

[Effect and side effects of a depot theophylline preparation within the scope of a clinical trial].

Author: WilkeA, WeineckeA, WeideW, SchäferK, IwainskyH

Improved lung function
Side effects

Aminophylline-retard-preparation V 37 was effective in treating obstructive lung disease, but dosage adjustments were often required to achieve optimal therapeutic effects.

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.
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

9.

[Possibilities for optimizing therapy with theophylline preparations. Clinical effectiveness and side effects of microcrystalline theophylline].

Author: WiesnerB, SehrtI, IwainskyH

Asthma treatment

Microcrystalline theophylline improved subjective state of health, reduced beta2-stimulant consumption, and increased lung function in patients with stabilized bronchial asthma.

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

12.

Caffeine versus other methylxanthines for the prevention and treatment of apnea in preterm infants.

Author: MorescoLuca, SjögrenAlice, MarquesKeri A, SollRoger, BruschettiniMatteo

Improved outcomes
Respiratory drive
Uncertainty of efficacy

This study looked at the effectiveness of different methylxanthines, including caffeine, theophylline, and aminophylline, for treating apnea of prematurity.

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.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

13.

Caffeine and sport.

Author: SaundersBryan, da CostaLarissa Registro, de SouzaRicardo Augusto Silva, BarretoGabriel, MarticorenaFelipe Miguel

Improved exercise performance

Caffeine is a stimulant that can enhance athletic performance in various sports, including high-intensity endurance exercise, explosive efforts, resistance training, team sports, and combat sports. While caffeine is generally safe, athletes should be aware of potential side effects and its impact on sleep.

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

Language : English

14.

Developing and testing a clinical care bundle incorporating caffeine citrate to manage apnoea of prematurity in a resource-constrained setting: a mixed methods clinical feasibility study protocol.

Author: IrimuGrace, OkwaroFerdinand, ColemanJesse, WaiyegoMary, MurilaFlorence, ChombaDorothy, ParsimeiMillicent, ShitoteCynthia, OchiengRoseline, ShahJasmit, OgeroMorris, GinsburgAmy Sarah, AnserminoJ Mark, MachariaWilliam

AOP prevention

This study aims to develop an evidence-based care bundle that includes caffeine citrate for preventing and managing apnoea of prematurity (AOP) in tertiary healthcare facilities in Kenya. The bundle will address challenges in resource-constrained settings such as identifying eligible preterm infants and monitoring vital signs.

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

Language : English

17.

Remdesivir-Associated Significant Bradycardia: A Report of Three Cases.

Author: ShirvaniMaria, SayadBabak, ShojaeiLida, AminiAzadeh, ShahbaziForoud

Bradycardia
QTc prolongation

This study describes 3 patients with COVID-19 who experienced significant bradycardia and QTc prolongation after remdesivir administration.

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.

Language : English

18.

Theophylline in patients with syncope without prodrome, normal heart, and normal electrocardiogram: a propensity-score matched study verified by implantable cardiac monitor.

Author: BrignoleMichele, IoriMatteo, StranoStefano, TomainoMarco, RivasiGiulia, UngarAndrea, CarrettaDomenico, SolariDiana, NapoliPaola, DeharoJean Claude, GuieuRegis

Syncope prevention

This study investigates the efficacy of theophylline, a non-selective adenosine receptor antagonist, in preventing syncopal events in patients with non-classical neurally mediated syncope. This type of syncope is characterized by the absence of prodromes and low adenosine plasma levels. The study explores the potential of theophylline to prevent syncope in this patient group.

Clinical StudyResearch involving human participants to assess the safety, efficacy, and effects of an intervention/treatment.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

19.

[Machine Learning-based Prediction of Seizure-inducing Action as an Adverse Drug Effect].

Author: GaoMengxuan, SatoMotoshige, IkegayaYuji

Seizure-inducing side effect detection

A machine learning-based in vitro system may provide a new platform to pre-clinically detect seizure-inducing side effects of drugs. The system uses local field potentials recorded from acute mouse neocortico-hippocampal slices to identify seizure-inducing drugs.

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 : Japanese

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