Usage
Ephedrine and theophylline are typically prescribed together for the relief of bronchospasm and bronchoconstriction in conditions like asthma and other chronic obstructive pulmonary diseases. This combination is not commonly prescribed now as safer and more effective alternatives exist.
Pharmacological Classification: Bronchodilator (combined sympathomimetic and xanthine derivative)
Mechanism of Action: Theophylline acts as a bronchodilator by relaxing the smooth muscles around the airways. It is also a phosphodiesterase inhibitor, leading to increased intracellular cAMP, further contributing to bronchodilation. Ephedrine also promotes bronchodilation by stimulating beta-2 adrenergic receptors in the lungs and stimulating norepinephrine release which in turn activates those receptors.
Alternate Names
The combination of ephedrine and theophylline is often referred to as theophylline-ephedrine compound.
Brand Names: Franol (Note: Brand names may vary regionally and some may no longer be available. This combination product has fallen out of favor and may no longer be marketed).
How It Works
Pharmacodynamics: Theophylline relaxes bronchial smooth muscle, leading to bronchodilation. Ephedrine, through its sympathomimetic action, also causes bronchodilation, increases heart rate, and constricts blood vessels, increasing blood pressure.
Pharmacokinetics:
- Absorption: Both drugs are absorbed orally. Theophylline absorption can vary depending on the formulation. Ephedrine is rapidly absorbed.
- Metabolism: Theophylline is primarily metabolized in the liver by CYP450 enzymes. Ephedrine is metabolized to norephedrine.
- Elimination: Theophylline is eliminated primarily through renal excretion, while ephedrine and its metabolites are also excreted renally.
Mode of Action: Theophylline inhibits phosphodiesterase enzymes, leading to increased intracellular cAMP levels, which relaxes smooth muscles. It also antagonizes adenosine receptors which may contribute to its bronchodilatory effect. Ephedrine directly and indirectly stimulates beta-2 adrenergic receptors in the lungs causing bronchodilation and also stimulates alpha-adrenergic receptors causing vasoconstriction.
Receptor Binding/Enzyme Inhibition: Theophylline inhibits phosphodiesterase enzymes and antagonizes adenosine receptors. Ephedrine stimulates alpha and beta-adrenergic receptors.
Elimination Pathways: Primarily renal excretion for both drugs. Theophylline metabolism involves CYP450 enzymes.
Dosage
Theophylline and ephedrine as a fixed-dose combination is not commonly prescribed. Because of the potential for adverse effects, theophylline and ephedrine should not be used together unless prescribed by a physician. There is no recommended dosing for the combination at this time.
Side Effects
Common Side Effects
- Nervousness
- Insomnia
- Tremors
- Nausea
- Vomiting
- Gastrointestinal upset
- Headache
- Dizziness
- Tachycardia
- Palpitations
Rare but Serious Side Effects
- Seizures
- Cardiac arrhythmias
- Hypertension
- Stroke
Contraindications
- Hypersensitivity to ephedrine or theophylline
- Severe hypertension
- Coronary artery disease
- Hyperthyroidism
- Seizure disorders
- Prostatic hypertrophy
Drug Interactions
- Caffeine and other xanthines: Increased risk of side effects
- Beta-blockers: Reduced bronchodilatory effect
- MAO inhibitors: Risk of hypertensive crisis
- Cardiac glycosides: Increased risk of arrhythmias
- CYP450 inducers/inhibitors: Altered theophylline levels
Pregnancy and Breastfeeding
Ephedrine is categorized as Pregnancy Category C. Theophylline is considered generally safe during pregnancy but serum levels should be monitored. It is not recommended to breastfeed while taking either of these medications.
Drug Profile Summary
- Mechanism of Action: Bronchodilation through different pathways. Theophylline inhibits phosphodiesterase and antagonizes adenosine receptors, while ephedrine stimulates adrenergic receptors.
- Side Effects: Nervousness, insomnia, tremors, nausea, vomiting, gastrointestinal upset, headache, dizziness, tachycardia, palpitations, seizures (rare), cardiac arrhythmias (rare).
- Contraindications: Hypersensitivity, severe hypertension, coronary artery disease, hyperthyroidism, seizure disorders.
- Drug Interactions: Caffeine, beta-blockers, MAO inhibitors, cardiac glycosides, CYP450 inducers/inhibitors.
- Pregnancy & Breastfeeding: Consult a physician. Monitor theophylline levels during pregnancy if used. Breastfeeding is not recommended.
- Dosage: A fixed-dose combination is not routinely prescribed.
- Monitoring Parameters: Serum theophylline levels, heart rate, blood pressure, ECG.
Popular Combinations
The combination of theophylline, ephedrine, and a barbiturate (like phenobarbital) was previously available under brand names such as Tedral, but has been discontinued. It should be noted that this combination had increased risks of adverse reactions.
Precautions
- Monitor cardiac function and blood pressure, particularly in patients with cardiovascular disease.
- Use with caution in patients with hyperthyroidism, seizure disorders, prostatic hypertrophy, diabetes.
- Avoid in patients with hypersensitivity to either drug.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Ephedrine + Theophylline?
A: A fixed-dose combination is generally not prescribed. Individualized dosing of each component may be considered in specific situations under the guidance of a physician if other treatments are ineffective or unavailable. Safer and more effective medications for asthma are available, so this combination is not preferred and is rarely used.
Q2: What are the major side effects of this combination?
A: Common side effects include nervousness, insomnia, tremors, nausea, and tachycardia. Rare but serious side effects include seizures and cardiac arrhythmias.
Q3: Is this combination safe during pregnancy?
A: It is recommended to consult a physician before using ephedrine or theophylline during pregnancy. The potential benefits must be carefully weighed against the risks. Alternatives may be preferred.
Q4: What are the key drug interactions to be aware of?
A: Significant interactions can occur with caffeine, beta-blockers, MAO inhibitors, cardiac glycosides, and drugs that affect CYP450 enzyme activity.
A: Primarily by CYP450 enzymes in the liver.
Q6: Why is this fixed combination not recommended?
A: Due to the increased risk of adverse effects and the availability of safer and more effective alternatives for asthma and COPD management.
A: Patients with cardiovascular disease, hyperthyroidism, seizure disorders, prostatic hypertrophy, and diabetes.
Q8: What should be monitored in patients taking theophylline?
A: Serum theophylline levels should be monitored to ensure they are within the therapeutic range and to minimize toxicity. Heart rate, blood pressure, and ECG should also be monitored, especially when used in combination with ephedrine.
Q9: Are there any dietary restrictions while taking this combination?
A: Patients should limit their intake of caffeine-containing products (coffee, tea, chocolate) as they can exacerbate the side effects of theophylline and ephedrine.
