Astemizole is a so-called antihistamine, which is used to treat allergies symptomatically. However, this drug is no longer available on the German market.
What is astemizole?
Astemizole is a so-called antihistamine, which is used to treat allergies symptomatically. Astemizole is an H1 receptor antagonist as well as a second-generation antihistamine. By blocking the histamine receptors, astemizole eliminates or at least attenuates the formation of the neurotransmitter histamine. Unlike first-generation preparations, astemizole cannot cross the blood–brain barrier and thus cannot enter the central nervous system. Astemizole, like similar preparations, came onto the market in 1984. In Germany and Austria, this preparation was marketed under the brand name Hisamanal. In the meantime, this preparation has been withdrawn from the market in most countries. The reason: in rare cases, it can interact strongly with some enzyme inhibitors. However, further research is being conducted with the drug. One possible area of application in the future could be tumor therapy.
Pharmacologic action
Astemizole has been used to treat allergic conjunctivitis, allergic rhinitis, hay fever, and hives and administered orally. The active ingredient binds H1 receptors in blood vessels, bronchial musculature, gastrointestinal tract, and uterus. In the gastrointestinal tract, astemizole is rapidly absorbed by the body, giving it a half-life of only 24 hours. Because the active ingredient binds to a receptor, astemizole is called a competitive antagonist. In other words, the active ingredient occupies the receptors and forms a complex with them. By displacing the neurotransmitter histamine from the H1 receptors, astemizole has an anti-allergic effect. This means that symptoms such as itching, swelling and reddening of the skin do not occur. In addition, the preparation has an anticholinergic effect because it also docks onto the muscarinic receptors. This is a membrane-resistant receptor in which acetylcholine, one of the most important neurotransmitters in the human organism, is produced. This plays an important role in the transmission of excitation between nerves and muscles, for example. This messenger substance is linked to numerous cognitive processes, which is why it is also an important factor in connection with diseases such as Alzheimer’s disease. This is because this disease is also manifested by a deficiency of that messenger substance.
Medical application and use
The drug astemizole was used to weaken or completely cancel the effect of the neurotransmitter histamine. The most important application is considered to be the treatment of allergic symptoms. These include itching and reddening of the skin as well as inflammation of the body and conjunctiva of the eye. First-generation H1 antihistamines were replaced by preparations such as astemizole because the former were able to cross the blood–brain barrier very easily, allowing the active ingredients to penetrate the central nervous system rapidly. This significantly reduced the potential side effects. Second-generation preparations such as astemizole have now been withdrawn from the market in Germany and many other countries and have been replaced by newer preparations. These cause fewer side effects and also offer further therapeutic advantages. Due to its relatively long half-life of 24 hours, astemizole offered patients who tolerated the drug the advantage that once-daily administration was sufficient. Excretion of the drug, which was absorbed by the body mainly in the gastrointestinal tract, was via feces.
Risks and side effects
In addition to milder side effects such as dry mouth, fatigue, and gastrointestinal disturbances, astemizole had mainly cardiac side effects. For example, in addition to cardiac arrhythmias, the drug could cause cardiac arrest or ventricular fibrillation. Although these side effects occurred rarely, they were very severe. For this reason, the use of astemizole was completely discontinued in numerous countries, and greatly reduced in others. Side effects affecting the heart have been found to be particularly severe in patients who have suffered from liver damage or QT prolongation. The reason for this is that potassium channels are blocked within the heart muscle.In extreme cases, this blockage can lead to torsades de pointes tachycardia, which is manifested by a heart rate of 150 beats per minute. In extreme cases, this can progress to ventricular fibrillation, posing a life-threatening situation for the patient.
