Usage
Salbutamol + Theophylline is prescribed for the relief of bronchospasm in various respiratory conditions, including:
- Bronchial asthma (all types)
- Chronic bronchitis
- Emphysema
Pharmacological Classification: Bronchodilator (combining a β₂-adrenergic agonist and a methylxanthine)
Mechanism of Action: Salbutamol acts as a short-acting β₂-adrenergic agonist, relaxing bronchial smooth muscle. Theophylline, a methylxanthine, inhibits phosphodiesterase enzymes, leading to increased intracellular cAMP levels, bronchodilation, and some anti-inflammatory effects.
Alternate Names
No widely recognized alternate names exist for the combination product itself. Individual components have other names:
- Salbutamol: Albuterol (USAN)
- Theophylline: Theophylline anhydrous
Brand Names: Jopamol-F, DuoNeb, Asthalin Theophylline (various combinations exist with different brand names)
How It Works
Pharmacodynamics: Salbutamol rapidly relaxes bronchial smooth muscle, relieving bronchospasm. Theophylline has a slower onset but longer duration of bronchodilation. It also has mild anti-inflammatory and immunomodulatory effects.
Pharmacokinetics:
- Absorption: Salbutamol is well-absorbed orally. Theophylline absorption varies depending on the formulation (immediate-release vs. extended-release).
- Metabolism: Salbutamol is primarily metabolized in the liver. Theophylline is extensively metabolized by the liver via CYP450 enzymes (CYP1A2, CYP2E1, CYP3A4).
- Elimination: Salbutamol is excreted primarily in the urine. Theophylline is also mainly excreted in the urine.
Mode of Action: Salbutamol binds to β₂-adrenergic receptors on bronchial smooth muscle, activating adenylate cyclase, increasing cAMP, and leading to muscle relaxation. Theophylline inhibits phosphodiesterase enzymes, preventing cAMP breakdown and promoting bronchodilation. It also has other proposed mechanisms, including adenosine receptor antagonism and modulation of intracellular calcium.
Receptor Binding: Salbutamol: β₂-adrenergic receptor agonist. Theophylline: Adenosine receptor antagonist.
Enzyme Inhibition: Theophylline: Phosphodiesterase inhibitor.
Neurotransmitter Modulation: No direct neurotransmitter modulation by either drug in this context.
Elimination Pathways: Both Salbutamol and Theophylline are predominantly eliminated via renal excretion.
Dosage
Standard Dosage
Adults: Salbutamol: 2-4mg three or four times daily, up to a maximum of 8mg per dose. Theophylline: Dosage is adjusted based on serum levels (therapeutic range: 10-20 mcg/mL).
Children (2-12 years): Salbutamol: 1-2 mg (2-6 years) or 2 mg (6-12 years) three or four times daily. Theophylline: Dosage is weight-based and should be carefully titrated based on serum levels.
Special Cases:
- Elderly Patients: Start with lower doses of both drugs and titrate cautiously.
- Patients with Renal Impairment: Reduce theophylline dose based on creatinine clearance.
- Patients with Hepatic Dysfunction: Reduce theophylline dose and monitor closely for adverse effects.
- Patients with Comorbid Conditions: Consider drug interactions and potential exacerbations of pre-existing conditions.
Clinical Use Cases
Dosage adjustments are based on clinical response and serum theophylline levels. Consult specialized resources for detailed guidelines for specific clinical scenarios like intubation, surgical procedures, mechanical ventilation, and ICU use. In emergency situations, IV formulations of salbutamol and/or aminophylline may be used under close monitoring.
Dosage Adjustments
Dose adjustments are necessary for patients with renal or hepatic impairment, metabolic disorders, or genetic polymorphisms affecting drug metabolism. Monitor serum theophylline levels to guide dosage and minimize toxicity.
Side Effects
Common Side Effects:
- Tremor
- Palpitations
- Tachycardia
- Headache
- Nausea
- Insomnia
- Irritability
Rare but Serious Side Effects:
- Seizures
- Cardiac arrhythmias
- Hypotension
- Hyperglycemia
- Hypokalemia
Long-Term Effects:
- Tolerance to bronchodilator effects (with theophylline)
- Osteoporosis (with long-term corticosteroid use, often co-prescribed)
Adverse Drug Reactions (ADR):
- Severe hypokalemia
- Cardiac arrhythmias (ventricular tachycardia, fibrillation)
- Seizures
- Anaphylaxis (rare)
Contraindications
- Hypersensitivity to either drug
- Non-i.v. formulations of salbutamol are contraindicated in uncomplicated premature labor or threatened abortion.
Drug Interactions
- β-blockers (antagonize salbutamol’s effects)
- Xanthines (additive effects with theophylline)
- Certain antibiotics (macrolides, fluoroquinolones - can increase theophylline levels)
- CYP450 inducers/inhibitors (affect theophylline metabolism)
Pregnancy and Breastfeeding
- Salbutamol: Generally considered safe during pregnancy and breastfeeding, but use with caution.
- Theophylline: Crosses the placenta and enters breast milk. Potential for fetal and neonatal toxicity. Use with caution during pregnancy and breastfeeding.
Drug Profile Summary
- Mechanism of Action: Bronchodilation via β₂-agonism (salbutamol) and phosphodiesterase inhibition (theophylline).
- Side Effects: Tremor, palpitations, tachycardia, headache, nausea, insomnia.
- Contraindications: Hypersensitivity.
- Drug Interactions: β-blockers, xanthines, certain antibiotics, CYP450 inducers/inhibitors.
- Pregnancy & Breastfeeding: Use with caution.
- Dosage: See detailed dosage section above.
- Monitoring Parameters: Serum theophylline levels, lung function, potassium levels, blood glucose.
Popular Combinations
Salbutamol + Theophylline is itself a popular combination. Inhaled corticosteroids are often added for long-term asthma control.
Precautions
- Monitor for side effects, especially in elderly patients and those with renal or hepatic impairment.
- Check serum theophylline levels regularly.
- Avoid abrupt discontinuation of theophylline.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Salbutamol + Theophylline?
A: See detailed dosage section above. Dosage varies depending on age, medical condition, and individual patient response.
Q2: What are the common side effects?
A: Common side effects include tremor, palpitations, tachycardia, headache, nausea, and insomnia.
Q3: What are the serious side effects?
A: Serious side effects can include seizures, cardiac arrhythmias, and severe hypokalemia.
Q4: Can this combination be used during pregnancy?
A: Both drugs should be used with caution during pregnancy and breastfeeding. Consult specialized resources for specific recommendations.
Q5: What are the drug interactions I should be aware of?
A: Important interactions include β-blockers, other xanthines, certain antibiotics, and CYP450 inducers/inhibitors.
A: Theophylline is extensively metabolized in the liver by the CYP450 enzyme system.
Q7: What should I monitor in patients taking this combination?
A: Monitor serum theophylline levels, lung function, potassium levels, blood glucose, and heart rate.
Q8: What are the contraindications to using this drug?
A: Contraindications include hypersensitivity to either drug and the use of non-IV salbutamol in uncomplicated premature labour or threatened abortion.
Q9: Should the dosage be adjusted for elderly patients?
A: Yes, elderly patients typically require lower doses due to age-related changes in drug clearance.
Q10: Are there any specific precautions for patients with liver or kidney problems?
A: Patients with liver or kidney dysfunction require dosage adjustments and close monitoring.
