For asthma, do not use formoterol alone for a long time

Asthma is a chronic airway disease. The clinical manifestations are recurrent wheezing, shortness of breath, chest tightness, or coughing. It needs to be treated with anti-asthmatic drugs. Antiasthmatic drugs refer to drugs that can act on different parts of the onset of asthma to relieve or prevent asthma attacks. Commonly used anti-asthmatic drugs can be divided into 6 categories: ① β adrenal receptor agonists; ② M choline receptor antagonists; ③ xanthine drugs; ④ allergy mediator release agents; ⑤ adrenal glucocorticoids; ⑥ anti-leukotrienes drug.

Among them, β adrenergic receptor agonists include non-selective β receptor agonists and (selective) β 2 receptor agonists. β2 receptor agonists mainly stimulate the β2 receptors of the respiratory tract, activate adenylate cyclase, increase the content of cyclic adenosine monophosphate (cAMP) in cells and decrease free calcium ions, thereby relaxing bronchial smooth muscle and inhibiting the release of inflammatory cells Allergic reaction mediators, enhance cilia movement and mucus clearance, reduce vascular permeability, reduce respiratory tract edema, and thus play an anti-asthmatic effect. For example, salbutamol and terbutaline are short-acting β2 receptor agonists. In recent years, people have also developed long-acting β2 receptor agonists that are more selective for β2 receptors and last longer, including today’s protagonist-formoterol.

Good absorption, quick onset and long acting time
Formoterol is a β2 receptor agonist developed by a Japanese company. Its tablets were first marketed in Japan in March 1986 for the treatment of chronic bronchial asthma, nocturnal asthma, exercise asthma, chronic obstructive pulmonary disease and children’s non-asthma Sexual respiratory disease.

Formoterol has a strong and continuous bronchiectasis effect, which can dilate the trachea and reduce airway resistance after a few minutes of inhalation, and this effect is significantly stronger than the same dose of salbutamol and terbutaline. Oral absorption is good, and it takes effect 30 minutes after taking it, and the maximum effect is reached after about 4 hours; it takes effect within 5 minutes after inhalation, and reaches a peak in about 2 hours, and it is excreted by the kidneys.

Short-acting β2 receptor agonists, such as salbutamol, can be selected for acute asthma attacks. Since formoterol has a stronger bronchodilator effect than salbutamol, has a faster onset and a longer duration (about 12 hours), can formoterol be used alone during an acute asthma attack? the answer is negative. It has been clinically found that long-acting β2 receptor agonists can increase the risk of death related to asthma. Therefore, it is only used for patients who are not adequately controlled by other asthma drugs, or those who are seriously ill and need to start using two drugs including this drug. , Not used alone for acute attacks of asthma.

Bronchial asthma is a chronic airway inflammation involving a variety of inflammatory cells, including eosinophils (EOS), mast cells, lymphocytes, epithelial cells, etc. and their cellular components. EOS plays a particularly critical role. Aggregated activated EOS can secrete a variety of inflammatory substances, participate in airway inflammation and airway remodeling, and also participate in suppressing the airway immune response.

Formoterol has anti-allergic and anti-inflammatory effects, can resist increased vascular permeability, can inhibit the aggregation of EOS induced by antigen, and can also inhibit the aggregation of EOS induced by platelet activating factor, and can also inhibit mast cell mediators. The release of histamine is similar to histamine H1 receptor antagonists (such as loratadine) and mast cell stabilizers (such as ketotifen). Clinical studies have shown that formoterol can reduce the content of eosinophil cationic protein (ECP) in lung tissue; some studies have shown that formoterol can inhibit the activation of EOS by inhibiting platelets or fibroblasts in a variety of ways. , Reduce the release of inflammatory mediators.

The use of formoterol has obvious anti-inflammatory effects, which can significantly inhibit antigen-induced EOS aggregation and infiltration, and increase in vascular permeability; it also has a significant protective effect on microvascular leakage and pulmonary edema caused by inhaled histamine. It is often used clinically. Other drugs are used in combination for the treatment of immediate and delayed asthmatic reactions and pulmonary edema.

Individualized medication, pay attention to the correct use method
The fumarate of formoterol is commonly used clinically, namely formoterol fumarate. Its tablets are mainly used to relieve symptoms such as dyspnea caused by airway obstructive diseases such as bronchial asthma, acute bronchitis, asthmatic bronchitis or emphysema. Adults take formoterol fumarate tablets 40-80μg (micrograms) twice a day; children take formoterol fumarate tablets 4μg per kilogram of body weight daily, divided into 2 to 3 times. The dosage can be appropriately increased or decreased according to age and symptoms.

Formoterol fumarate powder inhalation is used to treat and prevent reversible airway obstruction. In maintenance therapy, this product is also suitable as an additional drug for anti-inflammatory treatment. This dosage form is administered as an inhalation, the dosage should be individualized, and the lowest effective dosage should be used as much as possible. Due to lack of safety and effectiveness data, it is not recommended for children under 6 years of age. For adults, the conventional dose is 12 μg once or twice a day, administered in the morning and/or evening. Some patients need to increase the dose, 1 to 2 times a day, 12 to 24 μg each time, up to 48 μg per day. Asthma attacks at night, and can be administered once in the evening. This product should not (not enough) be used in the first-line treatment of asthma.

The adverse reactions of formoterol are headache, palpitations, and tremor. Occasionally, irritability, restlessness, insomnia, muscle cramps, and tachycardia may occur; tremor and palpitations may appear, usually transient, and decrease with the progress of treatment; rashes, urticaria and bronchospasm are rare.

There are the following precautions in clinical application:

1. People who are allergic to this product are prohibited.

2. Cardiovascular disorders, diabetes, liver insufficiency, hypokalemia, pheochromocytoma, renal insufficiency, hyperthyroidism patients and pregnant women should be used with caution; the safety of medication for premature infants and newborns has not been determined.

3. Use the medicine correctly under the guidance of a doctor. If the effect is not seen after correct usage according to the usage and dosage, the drug should be considered unsuitable and the administration should be terminated. When administering medicine to children, it is necessary to correctly guide the usage method and closely observe the treatment process.

4. Continuous over-dose may cause arrhythmia and sometimes cardiac arrest, so be careful not to over-dose.

5. Like all β2 receptor agonists, hyperthyroidism, pheochromocytoma, hypertrophic infarct cardiomyopathy, idiopathic submembranous aortic stenosis, severe hypertension, internal carotid artery-posterior communicating artery aneurysm, or other Patients with severe cardiovascular disease (myocardial ischemia, tachycardia or severe heart failure) should be used with caution. Formoterol can cause Q-TC interval prolongation, so patients with Q-TC interval prolongation and the use of drugs that affect Q-TC interval (such as astemizole, terfenadine, loratadine, cissar) Pride, ciprofloxacin, ofloxacin, levofloxacin, gatifloxacin, moxifloxacin, amiodarone, quinidine, etc.) should be used with caution.

6. β2 receptor agonists affect blood glucose metabolism. In the early stage of medication, patients with diabetes should pay attention to blood sugar control.

7. Because of its activation of beta receptors, it may cause hypokalemia. Combination of theophylline drugs, steroid drugs and diuretics may enhance the effect of hypokalemia. You should pay more attention to acute asthma attacks, as hypoxia can increase this risk. Combination medication may also increase the risk of hypokalemia. Therefore, in the above cases, it is recommended to monitor blood potassium concentration.

8. If β-receptor blockers are used at the same time, including the use of eye drops (such as timolol eye drops), the effect of this drug may be inhibited.

Long-term single use is not recommended, combined with glucocorticoids are more effective
Long-term, single-use long-acting β2 receptor agonists (such as formoterol, salmeterol) will cause certain damage to liver and kidney function, and will also have certain effects on the digestive system, and may also lead to the body’s resistance to drugs. The sensitivity is reduced and the use effect cannot be achieved. Studies have shown that airway allergic inflammation is the main pathological feature of asthma, so inhibiting airway inflammation is one of the fundamental measures to treat asthma. The use of long-acting β2 receptor agonists can reduce or disappear asthma symptoms, but alone cannot treat the underlying inflammatory response. Instead, it will cause the illusion that asthma is cured. Once patients encounter predisposing factors, they are likely to experience asthma exacerbation. And because the persistent airway inflammation has not been controlled, its condition will gradually worsen overall, and there is even a risk of death from asthma. Although the incidence is very low, it requires vigilance.

Therefore, national guidelines suggest that long-acting β2 receptor agonists should always be used in combination with inhaled glucocorticoids, and only used when inhaled glucocorticoids cannot control asthma symptoms; when there is no conventional glucocorticoid to treat asthma Therefore, long-acting β2 receptor agonists should not be used to relieve symptoms of exercise-induced asthma.

Glucocorticoids can control chronic airway inflammation, and at the same time make the body more sensitive to β2 receptor agonists; long-acting β2 receptor agonists can relax bronchial smooth muscle in patients with reversible airway obstruction. The two types of drugs are combined It has synergistic anti-inflammatory and anti-asthmatic effects, and reduces the adverse effects of large doses of glucocorticoids and the use of long-acting β2 receptor agonists alone, achieving an effect of 1+1>2. Therefore, in clinical treatment, formoterol and salmeterol are usually not used alone, but combined with glucocorticoids for nebulized inhalation, or use their compound preparations, such as budesonide formoterol powder inhalation (buddy A compound preparation of acetonide and formoterol, trade name Xin Bica Tubao), salmeterol ticasone powder inhalation (a compound preparation of fluticasone propionate and salmeterol, trade name seretide).

So how do you choose between Sibica Tubao and Seretide? We separate the two for comparison.

Let’s first look at budesonide and fluticasone propionate, both of which belong to glucocorticoids, which are mainly used to control inflammation and anti-allergic. While retaining high lipophilicity, budesonide has high hydrophilicity and is easier to penetrate the mucus layer of the airway to exert a rapid anti-inflammatory effect; it also has a high deposition rate in the lung and has a strong anti-inflammatory effect. Fluticasone propionate is more fat-soluble than budesonide and has stronger receptor affinity, but at the same time, because it is insoluble in water, it does not easily penetrate the hydrophilic layer of the airway mucosa and stays in the airway for a short time. The apparent volume of distribution is large, the half-life is long, the clearance in the lung is slowed, the effect is stronger than budesonide, the effect is longer, and the potential risk of systemic adverse reactions is greater than budesonide. But budesonide works faster. It is currently the only inhaled glucocorticoid approved by the U.S. Food and Drug Administration that can be used during pregnancy. In terms of safety during pregnancy, budesonide is even better.

Let’s look at salmeterol and formoterol. Both of them are long-acting selective β2 receptor agonists. In terms of time of action (both around 12 hours), there is no obvious difference between the advantages and disadvantages of the two drugs. If you have severe wheezing at night, it is recommended to use salmeterol, and formoterol for airway spasm, so different types of effects are emphasized. The onset time of formoterol (2 to 5 minutes) is faster than salmeterol (5 to 15 minutes). When an acute asthma attack occurs, we all hope to control the symptoms as soon as possible. The speed of formoterol is better than salmeterol. Luo. Therefore, formoterol can be used to quickly relieve the symptoms of asthma, but also can be used as a maintenance therapy, and salmeterol is more suitable for maintenance therapy. Formoterol is mostly metabolized by the liver and excreted in bile; while salmeterol is excreted in urine and feces with different elimination methods.

The last is the difference in inhalation devices. The inhalation device of Sibica Dubao is called “Dubao”, and the inhalation device of Seretide is called “Duobao”: ①Dubao is elongated, and the quasi-suction device is round. ②There is no counting window, and the remaining amount of medicine can only be judged by the change of color; the quasi-dose device has a counting window, which can accurately display the number of times remaining after inhalation. ③Dubao’s inhalation resistance is relatively large, which is not suitable for elderly patients, pediatric patients and patients with poor lung function; the inhalation resistance of the quasi-acceptor is relatively small, and it is easier to inhale, which is more suitable for the above patients. ④The lactose content in Dubao is relatively low. After inhalation, patients usually report that they have no sense of taste and do not know whether they have inhaled it; the content of lactose in the powder of the quasi-navigator is relatively high, and patients have a sense of taste after inhalation.

Overall, in terms of avoiding acute attacks of asthma, budesonide formoterol powder inhalation (Sibica Dubao) has more advantages than salmeterol ticasone powder inhalation (seretide). And if the liver function is insufficiency, it is recommended to choose salmeterol ticasone powder inhalation (seretide) to have relatively little effect on the liver. Finally, remind everyone that you must use a special inhalation device when using inhalants, and ensure that the inhalation device can be used correctly in strict accordance with the instructions.

>>Extended link to the usage and dosage of salbutamol
Salbutamol is a more well-known asthma treatment drug that we are more familiar with. There are many dosage forms such as tablets, capsules, aerosols, powder mists, injections and so on. Aerosol inhalation is often used when asthma attacks occur, and oral administration can be used to prevent attacks.

The dosage for adults is: (1) Oral, 2~4mg (mg) each time, 3 times a day; Aerosol inhalation, 0.1~0.2mg each time (ie spray 1~2 times), repeat every 4 hours if necessary 1 time, but not more than 8 times within 24 hours; intravenous injection, 0.4mg once, diluted with 5% glucose injection 20ml (ml) or sodium chloride injection 2ml and then slowly injected; intravenous drip, 0.4mg once, Dilute with 100ml of 5% glucose injection and instill it; intramuscular injection, 0.4mg once, if necessary, the injection can be repeated in 4 hours.

According to the recommendations of “China National Formulary (Volume of Chemical Medicines and Biological Products·Children’s Edition)”, the dosage of salbutamol for children is oral, 1 month to 2 years old, 0.1 mg/kg once, 3 to 4 times a day, the maximum once Dosage no more than 2mg; 2 to 6 years old, 1 to 2 mg once, 3 to 4 times a day; 6 to 12 years old, 2 mg once, 3 to 4 times a day; 12 to 18 years old, 2 to 4 mg once, 3 times a day ~4 times. Inhalation: ①Aerosol, administered for children 10-15 minutes before relieving symptoms or exercising and contact with allergens, 0.1-0.2mg each time; in the first hour of acute attack, it can be administered once every 20 minutes for a total of 3 consecutive times Times, and thereafter as needed every 2 to 4 hours. ②The solution is mainly used to relieve the symptoms of acute attacks. The minimum starting dose for children under 12 years old is 2.5 mg once, diluted with 1.5-2 ml of sodium chloride injection, and inhaled by a driven nebulizer; in the first hour of an acute attack, it can be administered once every 20 minutes for a total of Three times in a row, and then every 2 to 4 hours as needed.