Theophylline works in three distinct ways:. The bronchodilatory effect is not maximal at therapeutically effective dosages. Theophylline antagonizes adenosine receptors A1, A2 strongly, and A3 less potently. It binds to adenosine A2B receptors to prevent bronchoconstriction by inhibiting the release of mediators like histamine and leukotrienes from mast cells. Theophylline also increases calcium uptake through the adenosine-mediated calcium channels in the diaphragm leading to increased contraction and reversal of diaphragm fatigue.
This antagonism of the adenosine receptors, specifically A1 receptors, is responsible for some of the side effects of theophylline, like seizures and cardiac arrhythmias. In inflammatory states, histone deacetylase activity becomes reduced due to oxidative stress via the activation of phosphoinositidekinase-delta PI3K-Delta.
This mechanism is distinct from PDE and adenosine receptor inhibition. Recently, mitochondrial dysfunction has been linked to the development of chronic obstructive pulmonary disease COPD and asthma. A new study indicates that aminophylline plays an essential role in mitochondrial biogenesis in epithelial cells of the lung.
Consequently, aminophylline is believed to have a beneficial effect on epithelial mitochondrial function in lung diseases.
The remaining unbound theophylline distributes freely throughout the body except for body fat. The volume of distribution ranges from 0. It passes across the placenta and is present in breast milk. Theophylline metabolism occurs in the liver via the cytochrome CYP system. Pharmacokinetics of theophylline are not predictable by sex, age, or other characteristics. Besides, other factors like certain illnesses, tobacco use, marijuana use, and co-administration of other drugs can significantly alter its clearance.
Below is a list of factors affecting the clearance of theophylline. Aminophylline comes in the form of an oral solution, oral tablets, and extended-release- tablets. The absorption of the solution and oral tablets give wide fluctuations of serum concentrations and therefore are usually not recommended.
The extended-release tablets are absorbed slowly over 12 to 24 hours and provide a steady plasma concentration. Intravenous administration of aminophylline occurs via two methods. The dosage depends on theophylline clearance and whether the person has taken theophylline in the last 24 hours.
These dosages vary by age, body weight, and the health status of the patient. The loading dose is 5. This dose is for patients who have not taken aminophylline in the past 24 hours.
The loading dose calculation must use the formula given below for patients who have taken aminophylline in the last 24 hours. These dosage forms are not widely used due to inconsistent absorption and the occurrence of proctitis. Aminophylline has a narrow therapeutic index and is associated with a wide range of adverse effects.
The adverse effects depend on the peak serum concentrations of theophylline in the body. Aminophylline contraindications include patients with hypersensitivity to theophylline, ethylenediamine, or any component of the drug formulation.
Precautions are necessary for patients with concurrent illnesses like:. Aminophylline is a pregnancy category C drug and passes into breast milk and across the placenta. Therefore, consistent monitoring and dose adjustment can help prevent adverse effects in this population. Breastfeeding Avoid breastfeeding for 2 hours after intravenous or 4 hours after an oral aminophylline product to reduce the dose received by the breastfed infant.
Patients receiving aminophylline require monitoring for CNS effects, respiratory rate, arterial blood gasses, and serum theophylline concentrations. Clinicians must measure serum concentrations before initiating a loading dose in a person who has taken theophylline in the last 24 hours. A repeat serum concentration is necessary before starting the maintenance dose, as well.
Aminophylline toxicity can present with the following clinical features. Aminophylline is an adjunct to beta2-agonists and corticosteroids in treating reversible bronchoconstriction caused by asthma and chronic lung conditions. However, the drug demonstrates a narrow therapeutic index, and even with regular monitoring, it can lead to adverse effects.
Without precise management, the morbidity and mortality from aminophylline overdose are high. Therefore Healthcare workers, including nurses, pharmacists, and prescribing clinicians, should be aware of the complications of aminophylline toxicity.
Clinicians should prescribe aminophylline after risk-benefit evaluation for appropriate indications considering the recent global initiative for asthma GINA guidelines and global initiative for chronic obstructive lung disease GOLD guidelines. There is no specific antidote to reverse toxicity, so it is vital to avoid taking high doses without approval from the clinician. Nursing staff can monitor vital signs and treatment effectiveness and communicate with the healthcare team if they notice any adverse event.
The pharmacist should suggest a safer option for treating asthma to clinicians who prescribe this drug, verify dosing, perform thorough medication reconciliation, alert the team to any issues. Also, drug interactions and concurrent illnesses require strong consideration before initiating treatment as clearance rates vary widely. In cases of acute overdose, tirage nurses and emergency department physicians should rapidly stabilize patients and promptly initiate treatment.
Clinicians should consult intensivists for refractory seizures, arrhythmias, and hypotension. Nephrologist consultation is necessary for hemodialysis.
As illustrated above, multiple healthcare providers, including clinicians MDs, DOs, NPs, PAs , specialists, nurses, pharmacists, are involved in taking care of the patient receiving aminophylline therapy. Hence, only through a collaborative, interprofessional team approach can the morbidity of this medication be lowered while achieving improved outcomes.
American family physician. Iranian Red Crescent medical journal. Advances in experimental medicine and biology. The European respiratory journal. Hide glossary Glossary Study record managers: refer to the Data Element Definitions if submitting registration or results information. Search for terms. Save this study. Warning You have reached the maximum number of saved studies Effects of Aminophylline on Renal Function and Urine Volume of AKI Patient The safety and scientific validity of this study is the responsibility of the study sponsor and investigators.
Listing a study does not mean it has been evaluated by the U. Federal Government. Read our disclaimer for details. Recruitment status was: Not yet recruiting First Posted : December 6, Last Update Posted : December 6, Study Description.
This study evaluates the effects of aminophylline on serum creatinine and urine volume of AKI Patient. Half of participants will receive aminophylline and furosemide in combination,while the other half will receive only furosemide. Detailed Description:. Drug Information available for: Furosemide Aminophylline. FDA Resources. Arms and Interventions. Placebo bolus followed by IV infusions of normal saline 0. Outcome Measures. Secondary Outcome Measures : dose of norepinephrine [ Time Frame: Change from dose of norepinephrine at 2 weeks ] blood pressure [ Time Frame: Change from baseline systolic blood pressure at 2 weeks ] central venous pressure [ Time Frame: Change from central venous pressure at 2 weeks ].
Eligibility Criteria. Information from the National Library of Medicine Choosing to participate in a study is an important personal decision. Contacts and Locations. Information from the National Library of Medicine To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials. More Information. A pilot study to investigate the effects of an infusion of aminophylline on renal function following major abdominal surgery. Low-dose aminophylline for the treatment of neonatal non-oliguric renal failure-case series and review of the literature.
J Pediatr Pharmacol Ther. Pediatr Crit Care Med. Low-dose dopamine or low-dose nesiritide in acute heart failure with renal dysfunction: the ROSE acute heart failure randomized trial.
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