aminophylline, ephedrine and phenobarbitone

Action and Spectrum

Actions and spectrum: 

• aminophylline: aminophylline is a bronchodilator and smooth muscle relaxant. It helps relax the airway muscles, making it easier to breathe. It is primarily used to treat respiratory conditions like asthma and COPD. 
• ephedrine: ephedrine acts as a sympathomimetic agent, meaning it stimulates the sympathetic nervous system. It is a vasoconstrictor and bronchodilator. It is used to increase blood pressure and treat conditions like low blood pressure and nasal congestion. 
• phenobarbitone: phenobarbitone is a barbiturate that acts as a sedative and anticonvulsant. It helps to control seizures and may be used for certain types of epilepsy. 

This combination is typically prescribed to address a range of respiratory issues, including asthma attacks and bronchospasms, where its components work together to alleviate symptoms and improve breathing. 

Drug Interaction

Adverse Reaction

Frequency not defined 

Drowsiness 

Somnolence 

Nausea 

Depression 

Headache 

Ataxia 

Urticaria 

Hypotension 

Rash 

Hypothermia 

Nystagmus 

Confusion 

Vomiting 

Arrhythmias 

Tachycardia 

Nervousness 

Dizziness 

Anorexia 

Muscle weakness 

Insomnia 

Hypertension 

Abdominal pain 

Tremor 

Decreased appetite 

Irritability 

Increased urination 

Flushing 

Anxiety 

Black Box Warning

Black Box Warning: 

There were no specific black box warnings associated with aminophylline, ephedrine, and phenobarbitone. 

Contraindication / Caution

Contraindication/Caution: 

Contraindication: 

• Hypersensitivity: Contraindicated in individuals with a known hypersensitivity or allergy to any of the active ingredients or other components of the medication. 
• Epilepsy: phenobarbitone is an anticonvulsant and should not be used in patients with a history of hypersensitivity or severe adverse reactions to barbiturates. It may also interact with other antiepileptic drugs. 
• Closed-Angle Glaucoma: ephedrine can increase intraocular pressure and is contraindicated in patients with closed-angle glaucoma. 
• Thyroid Disorders: ephedrine can stimulate the release of thyroid hormones and should be used cautiously in patients with hyperthyroidism. 
• Pregnancy and Lactation: Depending on the specific formulation and circumstances, this combination may be contraindicated during pregnancy and breastfeeding. Each component should be evaluated individually for safety.

Caution: 

• Cardiovascular Conditions: Caution is advised when administering this combination to patients with underlying cardiovascular conditions, such as hypertension, arrhythmias, or coronary artery disease. These medications can have stimulant effects on the heart and blood vessels, potentially exacerbating cardiovascular issues. 
• Respiratory Conditions: Although aminophylline is used as a bronchodilator, caution is required in patients with underlying respiratory conditions, such as asthma or COPD. Close monitoring of respiratory function is necessary, as excessive bronchodilation can lead to adverse effects. 
• Central Nervous System (CNS) Depression: phenobarbitone is a central nervous system depressant, and its sedative effects can be potentiated when combined with other medications that affect the CNS, potentially leading to excessive sedation or drowsiness. This caution is especially relevant when considering the patient’s level of alertness and coordination. 
• Drug Interactions: aminophylline, ephedrine, and phenobarbitone may interact with various other medications, including over-the-counter drugs and herbal supplements. Healthcare providers should review the patient’s complete medication list to identify potential interactions.

Comorbidities: 

• Asthma and COPD: This combination can be used in patients with comorbid asthma or COPD who are experiencing acute exacerbations or severe bronchospasm. aminophylline helps relax the airway smooth muscles, ephedrine acts as a bronchodilator, and phenobarbitone may help suppress severe respiratory distress. 
• Status Epilepticus: aminophylline, ephedrine, and phenobarbitone may be used to manage status epilepticus, a life-threatening condition characterized by prolonged seizures. phenobarbitone has anticonvulsant properties, while aminophylline and ephedrine can help improve cerebral blood flow. 
• Anaphylaxis: In cases of severe allergic reactions that lead to bronchoconstriction and shock, this combination may be used to counteract bronchospasm and support blood pressure. 
• Cardiac Arrest: In cases of cardiac arrest, especially when associated with severe respiratory distress, this combination might be used to support ventilation and oxygenation. 
• Drug-Induced Hypotension: ephedrine, in combination with the other medications, can be used to treat severe hypotension caused by various medications or medical conditions. 

Pregnancy / Lactation

Pregnancy consideration: pregnancy category: not assigned 

Lactation: excreted into human milk: unknown   

Pregnancy category: 

• Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 
• <b>Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 
• Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.   
• Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits. 
• Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women. 
• Category N: There is no data available for the drug under this category. 

Pharmacology

Pharmacology: 

The combination of aminophylline, ephedrine, and phenobarbitone represents a pharmacological synergy designed to address specific medical emergencies. aminophylline, a xanthine derivative, acts as a bronchodilator by relaxing smooth muscles. ephedrine, a sympathomimetic agent, stimulates adrenergic receptors, leading to bronchodilation and increased cardiac output.

phenobarbitone is a barbiturate that possesses anticonvulsant properties and can help control seizures. Together, these drugs are used in acute situations such as severe asthma attacks, status epilepticus, or anaphylaxis, where rapid bronchodilation, improved oxygenation, and seizure control are essential.  

Pharmacodynamics: 

• aminophylline: aminophylline is a bronchodilator that works by inhibiting the enzyme phosphodiesterase, leading to increased levels of cyclic AMP (cAMP) within smooth muscle cells. Elevated cAMP levels result in the relaxation of bronchial smooth muscles, leading to bronchodilation. This effect helps improve airflow in the respiratory tract, making it easier for patients to breathe. 
• ephedrine: ephedrine is a sympathomimetic amine that acts by stimulating adrenergic receptors, particularly alpha and beta receptors. This stimulation leads to increased heart rate, cardiac output, and bronchodilation. ephedrine’s actions enhance cardiovascular function and can support blood pressure and oxygen delivery. 
• phenobarbitone: phenobarbitone is a barbiturate with anticonvulsant properties. It works by enhancing the inhibitory effects of GABA neurotransmitter in the central nervous system. This results in the suppression of abnormal electrical activity in the brain, making it effective in controlling seizures. 

The combined pharmacodynamic effects of these drugs make this combination therapy valuable in critical situations, such as severe asthma attacks or status epilepticus, where rapid bronchodilation, improved oxygenation, and seizure control are essential for patient management.  

Pharmacokinetics: 

aminophylline: 

• Absorption: aminophylline is typically administered orally or intravenously. When taken orally, it is absorbed from gastrointestinal tract. 
• Distribution: It distributes throughout the body, crossing cell membranes easily due to its small molecular size. It is bound to plasma proteins to some extent. 
• Metabolism: aminophylline is metabolized in the liver, primarily by the enzyme cytochrome P450 1A2, into its active form, theophylline. 
• Excretion: Theophylline, the active metabolite, is primarily excreted in the urine. The rate of excretion can be influenced by factors like age, liver function, and interactions with other drugs. 

ephedrine: 

• Absorption: ephedrine is well absorbed when administered orally. 
• Distribution: It is distributed throughout the body, including the central nervous system. It can also cross the placenta. 
• Metabolism: ephedrine is metabolized primarily in the liver. 
• Excretion: The metabolites of ephedrine are excreted in the urine. 

phenobarbitone: 

• Absorption: phenobarbitone can be administered orally or intravenously. It is well absorbed from the gastrointestinal tract. 
• Distribution: It has a relatively long half-life and distributes throughout the body. It can cross the blood-brain barrier. 
• Metabolism: phenobarbitone undergoes extensive hepatic metabolism. 
• Excretion: Metabolites are excreted in the urine. 

Adminstartion

Administration: 

• Oral Administration: Tablets or liquid forms of these medications can be taken orally. This is commonly used when the patient can tolerate oral intake. 
• Intravenous Administration: Intravenous administration is used in emergency situations or when rapid onset of action is required. A healthcare provider will administer the drugs directly into a vein. 
• Intramuscular administration: Intramuscular injections may be used when IV access is not readily available. The combination can be injected into a large muscle, such as the thigh or buttock. 
• Intratracheal Administration: In some cases, aminophylline can be administered directly into the trachea via an endotracheal tube when dealing with severe asthma exacerbations. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: aminophylline, ephedrine and phenobarbitone 

Pronounced: (A-min-oh-FIL-een, e-FED-rin, and FEE-no-BAR-bi-tone)  

Why do we use aminophylline, ephedrine and phenobarbitone? 

• Severe Asthma or COPD: aminophylline, a bronchodilator, is used to relax muscles and improve airflow. It can be administered in severe asthma or exacerbations of COPD when other treatments have not been effective. 
• Cardiac Arrest: ephedrine, a sympathomimetic agent, can be used to increase heart rate and blood pressure during cardiac arrest or severe hypotension when other measures are insufficient. 
• Status Epilepticus: phenobarbitone, an anticonvulsant, is used to treat and prevent status epilepticus, a prolonged and life-threatening seizure activity. 
• Respiratory Distress in Newborns: ephedrine may be used in neonates to treat apnea and episodes of bradycardia by stimulating the respiratory centers.