Aminophylline, Discovery, Action, Best Uses, Side effects, Precautions, Dosage and 12 Brands.

Introduction

Aminophylline belongs to a class of drugs called bronchodilators. It is used to treat various respiratory conditions, including asthma, chronic bronchitis, emphysema, and COPD (chronic obstructive pulmonary disease).

Aminophylline is a drug combination that contains theophylline and ethylenediamine in a 2:1 ratio it works by relaxing the muscles in the bronchial tubes (air passages) of the lungs, thereby increasing airflow and making it easier to breathe. Alleviating symptoms such as cough, wheezing, shortness of breath, and troubled breathing, plays a crucial role in managing these respiratory conditions.

Discovery of Aminophylline

The Discovery of Aminophylline: A Breakthrough in Respiratory Medicine

The discovery of Aminophylline represents a significant milestone in the field of respiratory medicine. It was discovered, its pharmacological properties, and its impact on the treatment of respiratory conditions.

Origins of Theophylline

The story of Aminophylline begins with the discovery of its parent compound, theophylline. Theophylline, a methylxanthine alkaloid, was first isolated from tea leaves in the early 19th century. Its stimulating effects on the central nervous system were noted, but its potential therapeutic applications remained largely unexplored.

Exploration of Bronchodilator Effects

In the late 19th and early 20th centuries, researchers began to investigate the pharmacological properties of theophylline. It was observed that theophylline had bronchodilator effects, leading to interest in its potential use for respiratory conditions.

Synthesis of Aminophylline

In the mid-20th century, medicinal chemists synthesized various derivatives of theophylline in search of compounds with enhanced therapeutic properties. It was created by adding an amino group to the theophylline molecule.

Pharmacological Properties

It was found to possess potent bronchodilator effects, making it a promising candidate for the treatment of asthma, chronic bronchitis, and other respiratory diseases. Additionally, It exhibited improved solubility compared to theophylline, enhancing its bioavailability and therapeutic efficacy.

Mechanism of Action

Aminophylline, a medication belonging to the class of bronchodilators, exerts its therapeutic effects through several distinct mechanisms. These mechanisms primarily target the smooth muscles lining the bronchial tubes (air passages) within the lungs, ultimately leading to bronchodilation and improved airflow. Here’s a detailed explanation of how Aminophylline works:

1. Bronchial Smooth Muscle Relaxation

Aminophylline acts directly on the smooth muscles surrounding the bronchial tubes, causing relaxation. Smooth muscle relaxation leads to the widening (dilation) of the air passages, allowing for increased airflow in and out of the lungs. This effect helps alleviate symptoms such as wheezing, coughing, and shortness of breath associated with respiratory conditions like asthma and chronic obstructive pulmonary disease (COPD).

2. Inhibition of Phosphodiesterase Enzymes

It inhibits the activity of phosphodiesterase enzymes, particularly phosphodiesterase 4 (PDE4). Phosphodiesterase enzymes are responsible for breaking down cyclic adenosine monophosphate (cAMP), a signalling molecule involved in regulating smooth muscle tone. By inhibiting PDE4, It increases the levels of cAMP within smooth muscle cells. Elevated cAMP levels lead to the relaxation of the bronchial smooth muscles, further promoting bronchodilation.

3. Antagonism of Adenosine Receptors

Aminophylline acts as an antagonist (blocker) of adenosine receptors, particularly the A1 and A2 receptors. Adenosine is a naturally occurring molecule that can induce bronchoconstriction (narrowing of the airways) when it binds to its receptors. Blocking these receptors, prevents the bronchoconstrictive effects of adenosine, thereby promoting bronchodilation and improving airflow in the lungs.

4. Stimulation of Respiratory Drive

It stimulates respiratory drive by acting on respiratory centres located in the brainstem. Enhancing the sensitivity of these respiratory centres to signals related to breathing increases respiratory rate and tidal volume. This stimulation facilitates gas exchange and improves oxygenation, particularly in individuals experiencing respiratory distress.

Forms of Aminophylline

Aminophylline is available in various pharmaceutical forms, allowing for flexible administration based on patient needs and medical requirements. The most common forms of Aminophylline include:

1. Oral Tablets: Aminophylline tablets are taken orally and are available in different strengths, typically ranging from 100mg to 400mg per tablet. They are commonly used for long-term management of respiratory conditions such as asthma and chronic obstructive pulmonary disease (COPD).
2. Oral Liquid/Syrup: Aminophylline oral liquid or syrup is a convenient option for patients who have difficulty swallowing tablets. It is available in different concentrations, allowing for precise dosage adjustments, particularly in pediatric patients or individuals with specific dosing requirements.
3. Intravenous (IV) Injection: It is administered intravenously for rapid onset of action, particularly in emergencies where immediate bronchodilation is needed. Intravenous its commonly used in hospital settings for the treatment of severe asthma exacerbations or acute respiratory distress.
4. Intramuscular (IM) Injection: It is administered via intramuscular injection, although this route of administration is less common compared to oral and intravenous routes.

Aminophylline Uses

Aminophylline, a medication belonging to the class of bronchodilators, is primarily used for the treatment of various respiratory conditions. Its medical uses include:

Asthma:

Aminophylline is widely utilized in the management of asthma, a chronic respiratory condition characterized by airway inflammation and bronchoconstriction. It helps alleviate symptoms such as wheezing, coughing, shortness of breath, and chest tightness during asthma attacks. By relaxing the bronchial smooth muscles, it promotes bronchodilation and improves airflow in the lungs.

Chronic Obstructive Pulmonary Disease (COPD):

Aminophylline is also prescribed for individuals with COPD, including chronic bronchitis and emphysema. It aids in relieving symptoms such as coughing, wheezing, and dyspnea (difficulty breathing), thereby improving lung function and quality of life for COPD patients.

Acute Exacerbations:

In cases of acute exacerbations of asthma or COPD, intravenous Aminophylline is administered in hospital settings to rapidly alleviate severe symptoms and improve respiratory function. It serves as an adjunct therapy alongside other treatments, such as corticosteroids and supplemental oxygen, during acute respiratory distress.

Bronchospasm:

It effectively treats bronchospasm, a sudden and reversible narrowing of the airways that can occur in various respiratory conditions. By relaxing the smooth muscles lining the bronchial tubes, Aminophylline helps relieve bronchospasm and restore normal breathing patterns.

Premature Labor:

It is used to prevent premature labour by relaxing the uterine muscles. Intravenous is administered under medical supervision to delay premature contractions and prolong pregnancy, particularly in high-risk situations.

Other Respiratory Disorders:

it is prescribed for other respiratory disorders characterized by airway constriction and breathing difficulties, such as bronchiolitis and bronchiectasis. However, its use for these conditions is less common compared to asthma and COPD.

Side effects

Aminophylline is effective in treating respiratory conditions, but it can also cause side effects in some individuals. It’s essential to be aware of these potential adverse reactions and to seek medical advice if they occur. Common side effects of aminophylline  include:

Nausea and Vomiting:

Some individuals experience nausea, and in some cases, vomiting, particularly when first starting aminophylline treatment. Taking the medication with food or dividing the dose into smaller, more frequent doses help alleviate these symptoms.

Gastrointestinal Disturbances:

Aminophylline can cause gastrointestinal discomfort, including stomach pain, abdominal cramps, and diarrhoea. Maintaining adequate hydration and adjusting the dosage or formulation of the medication may help mitigate these effects.

Headache:

Headaches are a common side effect of aminophylline therapy. If headaches become severe or persistent, it’s essential to inform a healthcare professional for further evaluation.

Insomnia or Sleep Disturbances:

Aminophylline is a central nervous system stimulant and causes insomnia or other sleep disturbances, particularly if taken close to bedtime. Taking the medication earlier in the day or adjusting the dosage helps reduce sleep-related side effects.

Tachycardia (Rapid Heart Rate):

Aminophylline can increase heart rate, leading to palpitations or feelings of a rapid or irregular heartbeat. Individuals with pre-existing cardiac conditions may be at higher risk of experiencing this side effect and should be closely monitored during treatment.

Tremors or Restlessness:

Some individuals experience tremors or feelings of restlessness while taking aminophylline. These effects are usually mild and improve over time as the body adjusts to the medication.

Hypokalemia (Low Potassium Levels):

Aminophylline can lower potassium levels in the blood, leading to symptoms such as muscle weakness, fatigue, and irregular heartbeat. Regular monitoring of electrolyte levels is necessary, particularly in individuals at risk of electrolyte imbalances.

Allergic Reactions:

In rare cases, aminophylline can cause allergic reactions, including skin rash, itching, swelling, or difficulty breathing. Any signs of an allergic reaction should be reported to a healthcare professional immediately.

Aminophylline precautions

General:

• Use with caution in patients with a history of seizure disorders, heart disease, or hypertension
• Monitor serum theophylline levels regularly
• Avoid sudden withdrawal or dose changes

Pregnancy and lactation:

• Use only when clearly needed and under medical supervision
• Monitor fetal heart rate and maternal serum theophylline levels
• Caution when breastfeeding, as theophylline is excreted in milk.

Pediatric use:

• Use with caution in children under 12 years old
• Monitor serum theophylline levels regularly
• Adjust the dose according to age and weight.

Drug interactions:

• Avoid concomitant use with other xanthines (e.g., caffeine)
• Monitor serum theophylline levels when co-administering with drugs that affect theophylline metabolism (e.g., cimetidine, erythromycin)
• Caution when co-administering with drugs that increase the risk of seizures (e.g., fluoroquinolones)

Other precautions:

• Use with caution in patients with a history of alcoholism or drug abuse
• Avoid smoking and excessive caffeine consumption
• Monitor for signs of theophylline toxicity (e.g., seizures, arrhythmias).

Dosage

The dosage for Aminophylline varies based on age, weight, and medical condition.
Here are some general guidelines:

• Adults: Loading dose: 5.7 mg aminophylline/kg (ideal body weight) intravenously over 30 minutes
  Maintenance dose: 0.5 mg aminophylline/kg ideal body weight/hour as a constant infusion
• Geriatric: Refer to adult dosing
  Maximum dose: 507 mg/day unless serum levels indicate the need for a larger dose
• Pediatric: Loading dose: 5.7 mg aminophylline/kg (ideal body weight) intravenously over 30 minutes
  Maintenance dose: 1 mg aminophylline/kg ideal body weight/hour as a constant infusion.

Please note that the dosage may vary depending on the patient’s condition and response to the medication. It is important to consult a healthcare professional for personalized advice and guidance.

Brands in Pakistan

Here are some brands of Aminophylline tablets along with their manufacturers:

1. Hydryllin DM Syrup (Manufacturer: Searle)
2. Cosome-E Syrup (Manufacturer: Zafa Pharmaceuticals)
3. Coldrex Syrup 120ml (Manufacturer: GSK (GlaxoSmithKline))
4. Pulmonal Syrup 120ml (Manufacturer: Hilton Pharma)
5. Hydryllin Syrup (Manufacturer: Searle)
6. Aminophylline – manufactured by Unexo Labs (Pvt) Ltd.
7. amphyll – manufactured by GlaxoSmithKline
8. asmolin – manufactured by Irza Pharma (Pvt) Ltd.
9. contophylin – manufactured by Rex Pharmaceuticals Pakistan
10. geophyllin – manufactured by Gaba Pharmaceuticals Labs
11. kohilin – manufactured by Kohs Pharmaceuticals
12. phyline tablet.