Usage
Aminophylline is primarily prescribed for the treatment and prophylaxis of bronchospasm associated with conditions like asthma, chronic obstructive pulmonary disease (COPD), and chronic bronchitis. It is also used in adults for the treatment of left ventricular and congestive cardiac failure. Pharmacologically, aminophylline is classified as a bronchodilator and a xanthine derivative. It works by relaxing the smooth muscles in the airways, allowing for easier breathing.
Alternate Names
Aminophylline is also known as theophylline ethylenediamine. Brand names vary depending on the region and manufacturer but can include Phyllocontin and Truphylline.
How It Works
Pharmacodynamics: Aminophylline exerts its bronchodilatory effects primarily through the inhibition of phosphodiesterase, leading to increased intracellular cyclic adenosine monophosphate (cAMP). This increase in cAMP relaxes bronchial smooth muscle. It also exhibits some adenosine receptor antagonism and may influence intracellular calcium levels.
Pharmacokinetics: Administered intravenously, aminophylline is rapidly absorbed. Orally, absorption can be variable depending on the formulation. It is metabolized in the liver, primarily by the cytochrome P450 enzymes CYP1A2, CYP2E1, and CYP3A4. Elimination occurs through renal excretion. The half-life is approximately 8.7 hours in healthy non-smoking adults but can vary significantly based on factors such as age, smoking status, and liver function.
Mode of Action: Aminophylline’s main mechanism of action involves nonselective inhibition of phosphodiesterase enzymes, especially phosphodiesterase 4, leading to an increase in cAMP levels. Elevated cAMP levels promote smooth muscle relaxation in the airways.
Receptor Binding, Enzyme Inhibition, or Neurotransmitter Modulation: Aminophylline inhibits phosphodiesterase enzymes and also acts as an adenosine receptor antagonist.
Elimination Pathways: Aminophylline is primarily eliminated through hepatic metabolism, followed by renal excretion.
Dosage
Standard Dosage
Adults:
- IV: Loading dose: 5-6mg/kg (ideal body weight), max 500mg, infused slowly over 20-30 minutes at a rate not exceeding 25mg/minute. Maintenance dose: 0.5-0.7 mg/kg/hour (0.3mg/kg/hour in elderly), adjustable based on plasma theophylline concentration.
- Oral: Initially, 225-450mg twice daily, increased if necessary. Modified-release formulations are available.
Children:
- IV: Loading dose: Same as adult dose. Maintenance dose (based on age and theophylline product): Refer to detailed product-specific guidelines. Pediatric dosages should be carefully calculated based on ideal body weight, and serum theophylline monitoring is crucial.
- Oral: >3 years: 12 mg/kg daily, increased to 24 mg/kg daily in two divided doses after one week (modified-release formulation).
Special Cases:
- Elderly Patients: Reduced doses are recommended (0.3 mg/kg/hour IV maintenance) due to age-related changes in clearance.
- Patients with Renal Impairment: Dose adjustments are required, based on creatinine clearance or glomerular filtration rate.
- Patients with Hepatic Dysfunction: Reduced doses are necessary due to impaired metabolism.
- Patients with Comorbid Conditions: Dosage adjustments may be needed for patients with heart failure, cor pulmonale, or other conditions affecting clearance.
Clinical Use Cases
Dosage adjustments should be made based on patient response and serum theophylline levels. Refer to product-specific guidelines for detailed recommendations in clinical settings such as intubation, surgical procedures, mechanical ventilation, ICU use, and emergency situations.
Dosage Adjustments
Dose modifications should be individualized based on factors like renal/hepatic function, smoking status, age, and concomitant medications.
Side Effects
Common Side Effects
Nausea, vomiting, headache, insomnia, irritability, restlessness, increased urine volume, shakiness, abdominal pain, diarrhea.
Rare but Serious Side Effects
Seizures, cardiac arrhythmias (including multifocal atrial tachycardia), persistent vomiting, CNS depression, allergic skin reactions, hepatotoxicity (indicated by elevated liver enzymes and jaundice).
Long-Term Effects
Potential long-term effects of aminophylline use are not well-established but may include dependence and tolerance.
Adverse Drug Reactions (ADR)
Serious ADRs include severe theophylline toxicity, seizures, and cardiac arrhythmias.
Contraindications
Acute porphyria, hypersensitivity to theophylline or ethylenediamine. Coronary artery disease where myocardial stimulation may be harmful.
Drug Interactions
Aminophylline interacts with numerous medications, including:
- CYP450 interactions: Cimetidine, erythromycin, ciprofloxacin, and fluconazole can inhibit theophylline metabolism, increasing serum levels. Rifampin, phenobarbital, and phenytoin can induce metabolism, decreasing serum levels.
- Other interactions: Lithium, beta-blockers, anticoagulants (like warfarin), and other sympathomimetics.
Pregnancy and Breastfeeding
Aminophylline is a pregnancy category C drug. It crosses the placenta and is excreted in breast milk. Use during pregnancy and breastfeeding should be carefully considered, weighing the benefits against the potential risks to the fetus or infant. Monitor infants for signs of irritability and stimulation.
Drug Profile Summary
- Mechanism of Action: Bronchodilation via phosphodiesterase inhibition and adenosine receptor antagonism.
- Side Effects: Nausea, vomiting, headache, insomnia, irritability, seizures, cardiac arrhythmias.
- Contraindications: Hypersensitivity, acute porphyria.
- Drug Interactions: Numerous drug interactions, notably with CYP450 inducers and inhibitors.
- Pregnancy & Breastfeeding: Category C; caution advised.
- Dosage: Individualized based on age, weight, and clinical status.
- Monitoring Parameters: Serum theophylline levels, ECG, heart rate, blood pressure, potassium levels.
Popular Combinations
Aminophylline is sometimes used in combination with other bronchodilators, such as beta-agonists, for additive effects.
Precautions
Careful dosage titration, monitoring of serum theophylline levels, and consideration of drug interactions are crucial. Pre-existing medical conditions, especially cardiac, renal, or hepatic dysfunction, require cautious use. Adjustments are necessary for elderly patients and smokers.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Aminophylline?
A: Dosage is individualized based on factors such as age, weight, medical condition, and route of administration. See the detailed dosage guidelines above.
Q2: What are the common side effects of Aminophylline?
A: Common side effects include nausea, vomiting, headache, insomnia, irritability, and restlessness.
Q3: What are the serious side effects of Aminophylline?
A: Serious side effects can include seizures, cardiac arrhythmias, and persistent vomiting.
Q4: What are the contraindications for Aminophylline?
A: Aminophylline is contraindicated in patients with hypersensitivity to the drug or acute porphyria.
Q5: How does Aminophylline interact with other medications?
A: Aminophylline interacts with numerous medications, particularly those affecting CYP450 enzyme activity. Consult a drug interaction database for detailed information.
Q6: Can Aminophylline be used during pregnancy and breastfeeding?
A: Aminophylline is a pregnancy category C drug and is excreted in breast milk. Use should be carefully considered, weighing the benefits against the potential risks.
A: Aminophylline is primarily metabolized in the liver and eliminated through renal excretion.
Q8: What monitoring parameters are important during Aminophylline therapy?
A: Monitor serum theophylline levels, ECG, heart rate, blood pressure, and potassium levels.
Q9: What are the key drug interactions to be aware of with Aminophylline?
A: Key interactions occur with CYP450 inducers and inhibitors, as well as certain antibiotics, beta-blockers, and anticoagulants.
