National Safe Medication Use Month丨“Second Generation Medicine” Ambroxol: Do you know how hard I try to eliminate phlegm?

Opening remarks

The 2023 "National Safe Medication Month" activity with the theme of "Safe Medication for the Health of the People" will be held from mid-November to mid-December. This activity will promote the concept and knowledge of safe medication through various forms to build a social consensus on drug safety. From now on, we will open a "Safe Medication Month" column to provide scientific interpretations on the safe use of drugs and further improve the public's health and scientific literacy.

Whether it is a common cold, acute or chronic bronchitis, or pneumonia, when there is phlegm in the respiratory tract that needs to be dealt with, ambroxol is indispensable. When used alone, ambroxol is available in tablets, injections, solutions, inhalers, sprays and other dosage forms. As a compound preparation, its "comrades-in-arms" include antibacterial drugs, β2 receptor agonists, glucocorticoids, antitussive drugs, etc. In addition, it can also be used in combination with other drugs to work together.

Why can ambroxol single-handedly hold up half of the market share of expectorants?

Expectorants that could have flourished

Why is phlegm so sticky?

The respiratory tract secretes fluid all the time. On the one hand, it keeps the respiratory tract moist. On the other hand, the respiratory tract secretions need to cooperate with the ciliary movement of the bronchial epithelium to expel dust, bacteria, etc. in the air.

Under normal circumstances, sputum will be "driven" into the digestive tract by cilia and will not cause discomfort. However, when the respiratory tract is inflammatory, the glands and goblet cells on the bronchus will secrete a large amount of mucin. At the same time, due to the death of a large number of inflammatory cells, the DNA remaining in the cell nucleus makes the sputum seem to be "thickened", and the viscosity increases significantly. In some cases, blocking the respiratory tract can be life-threatening.

In order to remove phlegm, people have found many medicines. According to the type, they are roughly divided into the following categories:

Sputum thinning drugs

There are nausea expectorants and irritant expectorants. Nausea expectorants stimulate the gastric mucosa, causing the vagus nerve to reflexively promote the secretion of bronchial glands, thereby diluting sputum. Representative drugs include ammonium chloride. Irritant expectorants are more straightforward, directly stimulating bronchial secretion and diluting sputum. Representative drugs include guaifenesin. This type of drug is still made into a single or compound oral medicine for use, but it is more irritating.

Mucolytics

This type of drug can destroy the disulfide bonds in mucin, degrade DNA in sputum, and reduce the viscosity of sputum. Representative drugs include acetylcysteine, carbocysteine, etc. This type of drug is also mainly taken orally. The smelly acetylcysteine ​​has an aerosol formulation, but there is no injection formulation for expectoration.

The above drugs have a very realistic problem to face: what about patients who cannot take the drug orally? For example, patients with dysphagia or poor gastrointestinal function, or uncooperative children, because there is no injectable dosage form available, the scope of application is limited.

It seems that there are many flowers blooming, but it always feels a little lacking. The field of expectorants urgently needs a "flower queen" to stabilize the scene.

The growth process of the “second generation of medicine”

Ambroxol can be injected, taken orally or nebulized, and its emergence has brought a turning point to the somewhat embarrassing expectorant.

In 1984, Ambroxol was first launched in Germany and came to my country in 1991. Compared with drugs that have a history of hundreds of years of use, it is not an old drug. In fact, Ambroxol is a "second-generation drug".

As early as 1963, a drug called bromhexine was developed and marketed by researchers after structural modification of a substance called dapoxetine. It was used to dissolve thick sputum.

The way bromhexine works is quite confusing: the first-pass effect is obvious, but it does not affect the efficacy. What does it mean? After the drug is taken orally, it needs to go through the liver before it can start to work. After bromhexine goes through this process, only about 1/5 of the drug can be used, and the other 4/5 are "repaired" by the liver.

This "repair" is not a big deal, the product of the repair is exactly ambroxol. And ambroxol is the active substance that really plays the role of expectorant.

Bromhexine is a drug that is inactive itself but has pharmacological effects as its metabolites in the body. It is called a prodrug. Prodrugs enter the body and then take effect after being metabolized. However, since it is the metabolite ambroxol that has the expectorant effect, why can't ambroxol be developed?

Thus, Ambroxol was launched on the market. It seems that Ambroxol came into the world by stepping on the shoulders of Bromhexine, and is an absolute "second-generation drug".

In clinical practice, people have found that bromhexine has more adverse reactions and its expectorant effect is not as good as ambroxol. As time goes by, bromhexine is gradually washed away by the waves behind it.

Ambroxol has been "working hard"

In order to achieve the ideal expectorant effect, ambroxol uses "four legs to walk".

1. Inhibit the release of DNA from the cell nucleus. The residual DNA in the nucleus of dead inflammatory cells can increase the viscosity of sputum. Ambroxol blocks this path first.

2. Inhibit the secretion of acidic mucopolysaccharides and mucins by the glands on the trachea and bronchi, and dissolve the acidic mucopolysaccharides that have already been produced. This blocks another way for sputum to become viscous.

3. Increase the secretion of respiratory fluid. The fluid can effectively dilute the viscous sputum and facilitate the discharge of sputum.

4. Promote the movement of bronchial cilia. Cilia can "scrub" faster and expel phlegm from the respiratory tract.

Ambroxol's expectorant ability can be described as a natural gift, and with the continuous expansion of its administration routes, its "efforts" have finally paid off. It has firmly occupied most of the expectorant market and firmly stood in the "C position" of expectorants.

Although it is excellent, it is not perfect. This is because the adverse reactions of ambroxol are still worth being vigilant about. Common adverse reactions include gastrointestinal reactions such as nausea and vomiting, nervous system reactions such as taste disorders, and rare severe skin adverse reactions. In addition, it is forbidden to use within 3 months of pregnancy, and pregnant and lactating women should use it with caution.

Although ambroxol has outstanding advantages, you should not be too "superstitious" about its efficacy when using it at home. If the symptoms of coughing and sputum do not improve after using it for a period of time, you should seek medical attention in time.