Asthma is a chronic condition that affects the airways in the lungs. The image shows the difference between a healthy bronchial airway (left) and a bronchial airway during an asthma attack (right). Exposure to asthma triggers can lead to inflammation and narrowing of airways in asthma patients, resulting in asthma attacks and breathing difficulties.[12] And Tedral exerts its therapeutic effects by decreasing airway responsiveness to allergens and relaxing the smooth muscle of the airways, thereby, making breathing easier.
The image above shows the difference between a normal, healthy lung (left) and a COPD patient's lung (right). Chronic obstructive pulmonary disease (COPD), is a progressive lung disease. The term COPD includes two main conditions: (1) emphysema and (2) chronic bronchitis. Emphysema develops when the walls of alveoli are destroyed, forming fewer larger alveoli. Chronic bronchitis is triggered by repeated or constant irritation and inflammation in the lining of airways. Bronchioles thus, lose their shape and become clogged with mucus.[17] These conditions result in difficulty in breathing. Symptoms can be improved by Tedral because of its bronchodilating property.
Mechanism of action
There are three active ingredients in Tedral and they have different mechanisms of action.
Second, theophylline is also a nonselective adenosine receptor antagonist, which acts on A1, A2, and A3 receptors with almost the same affinity. This possibly explains theophylline's cardiac effects. Adenosine-mediated channels also enhance diaphragmatic muscle contractility by promoting calcium uptake.
Other mechanisms of action of theophylline have also been proposed.[3] These include the inhibition of nuclear factor-kappaB prevents the translocation of the pro-inflammatory transcription factor (NF-kappaB) to the nucleus, thereby reducing the expression of known inflammatory genes in conditions such as COPD and asthma. Additionally, it increases the secretion of interleukin-10, which has broad anti-inflammatory effects. This process also decreases poly (ADP-ribose) polymerase-1 (PARP-1), promotes apoptosis of inflammatory cells, including T cells and neutrophils, and increases levels of histone deacetylase 2 by inhibiting phosphoinositide 3-kinase-delta.
It directly binds to both alpha and beta receptors. However, its primary mechanism of action is indirectly achieved by the inhibition of neuronal norepinephrine reuptake and displacement of more norepinephrine from storage vesicles. These actions prolong the presence of norepinephrine in the synapse for binding to postsynaptic alpha and beta receptors. Thereby, leading to alpha- and beta-adrenergic stimulation.[9]
Phenobarbital prolongs the time that chloride channels are open. Thereby, depressing the central nervous system. This is accomplished by acting on GABA-A receptor subunits. When phenobarbital binds to these receptors, the chloride ion gates open and remain open, allowing these ions to enter neuronal cells steadily. This action causes the cell membrane to hyperpolarize, leading to a raise in the action potential threshold.[5]
Adverse effects
Theophylline
Due to the presence of theophylline in Tedral, the most common side effects of this drug include:[3][6]
Phenobarbital also results in the adverse effects of Tedral. The most common side effects caused by phenobarbital are dizziness, sedation, incoordination, and impaired balance. However, these adverse effects affect geriatric patients to a greater extent.[5]
Concerning the adverse effects of phenobarbital after long-term usage, loss of appetite, depression, irritability, achiness in the bones, joints, or muscles, and liver damage may occur.[5]
Ephedrine raises both chronotropy and inotropy, increasing myocardial oxygen demand. Therefore, it has to be used in caution in patients with ischemic heart disease or heart failure. It should also be avoided in situations where tachycardia would be undesirable, for example aortic stenosis.[9]
Ephedrine's alpha-adrenergic stimulation causes contraction of the smooth muscle at the base of the bladder, resulting in resistance to urine output. It is, therefore, the use of Tedral in patients with urinary retention and prostatic hyperplasia has to be cautious.[9]
The history of Tedral can be traced back to the early 20th century when theophylline was first isolated from tea leaves and later found to have bronchodilator properties.[25] In the 1920s and 1930s, ephedrine was introduced as a treatment for asthma and other respiratory conditions due to its bronchodilating effect and ability to increase blood flow to the lungs.[26]
The combination of theophylline and ephedrine was first used in the 1940s as a treatment for asthma, and the addition of a barbiturate such as pentobarbital or phenobarbital was later added to enhance the sedative effects of the medication and improve patient compliance.[27]
Tedral was withdrawn from the US market in 2006 due to safety concerns related to the use of ephedrine. The US Food and Drug Administration (FDA) had previously issued warnings about the use of ephedrine-containing products due to their potential for serious side effects, including heart attack, stroke, and death.[30] In response, many pharmaceutical companies voluntarily removed their ephedrine-containing products from the market. In the case of Tedral, its manufacturer, Novartis Pharmaceuticals Corporation, voluntarily withdrew the medication from the market in 2006 after the FDA issued a warning letter to the company citing safety concerns related to the use of ephedrine.[31]
