phenobarbital + theophylline

The combination of phenobarbital and theophylline is a medication that has been used historically for respiratory conditions. This combination was often formulated with ephedrine as well, creating a three-component medication known by brand names such as Tedral. ## Composition and Mechanism of Action This combination contains two primary active ingredients: 1. **Phenobarbital**: A barbiturate that acts as a central nervous system depressant. It works by enhancing the inhibitory effects of GABA, a neurotransmitter that reduces brain activity. 2. **Theophylline**: A methylxanthine bronchodilator that relaxes bronchial smooth muscle and pulmonary artery smooth muscle. It works through multiple mechanisms: - Inhibits phosphodiesterase enzymes (particularly types III and IV) - Acts as a nonselective adenosine receptor antagonist - Inhibits nuclear factor-kappaB - Increases interleukin-10 secretion - Affects histone deacetylase 2 levels[6] ## Clinical Use and Status This combination was historically used to treat bronchial asthma, asthmatic bronchitis, and other bronchospastic disorders. However, it's important to note that products containing theophylline, ephedrine, and phenobarbital were withdrawn from the U.S. market by Parke Davis in April 1993[1]. The FDA withdrew new drug applications for products containing this combination. ## Drug Interactions A significant interaction exists between these two components. Phenobarbital can induce theophylline metabolism, which may decrease theophylline's effectiveness. Studies have shown that after phenobarbital therapy, there can be a significant increase in apparent theophylline clearance, accompanied by a decrease in steady-state serum theophylline concentration[2][3]. This interaction may require theophylline dosage adjustment in patients receiving both drugs concurrently. ## Side Effects The combination may cause various side effects including: - Drowsiness - Fast heartbeat - Headache - Muscle cramps - Nausea - Nervousness or restlessness - Trembling - Trouble sleeping[7] More serious side effects that may require medical attention include: - Heartburn and/or vomiting - Abdominal pain - Confusion or behavioral changes - Seizures - Dark or bloody vomit - Diarrhea - Dizziness - Irregular heartbeat[7]

Brand names

Tedral