How Do I Choose the Best Antihistamine for Allergies?

Antihistamine antiallergic drugs are divided into first-generation antihistamines, second-generation antihistamines and third-generation antihistamines, currently represented by diphenhydramine, chlorpheniramine, and promethazine, etc. The first-generation antihistamines were gradually replaced by second-generation antihistamines without sedation or mild sedation due to their strong central nervous system inhibitory effects. Some second-generation antihistamine drugs have been gradually reduced due to the obvious cardiotoxicity (such as terfenadine, astemizole, etc.), and third-generation agents such as fexofenadine, levocetirizine Antihistamines have come out.

Antihistamine

Antihistamine antiallergic drugs are divided into first-generation antihistamines, second-generation antihistamines and third-generation antihistamines, currently represented by diphenhydramine, chlorpheniramine, and promethazine, etc. The first-generation antihistamines were gradually replaced by second-generation antihistamines without sedation or mild sedation due to their strong central nervous system inhibitory effects. Some second-generation antihistamine drugs have been gradually reduced due to the obvious cardiotoxicity (such as terfenadine, aspartazol, etc.),

non-

Levocetirizine

[Commodity name] Xyral, disco

[In vivo process] Levocetirizine is the levorite of cetirizine, which has a high binding rate to plasma proteins after oral absorption into the blood. The effect of levocetirizine after 1 hour of oral administration is obvious, and the duration is 24.4 Hours, peaking within 6 hours. Pharmacokinetic studies confirm that racemic cetirizine, composed of two equal amounts of enantiomers, is not metabolized in the body by the liver. Plasma concentrations of levocetirizine are almost right after 4 and 8 hours of oral administration It is twice as much as dextrotirizine, and its metabolites are mainly excreted from the urine. After 32 hours of oral administration, 50% -60% of the drug is excreted in the urine, and a small amount is excreted in the feces.

[Pharmacological mechanism] Levocetirizine

[Commodity name] Enris; Fu Bi Ding; Clarinex; Neoclarityn; Aerius

Synonym DescarboethoxyIoratadine NEW 2001; Decarboxyloratadine; Deloratadine; Deethoxycarbonyl loratadine

[Chemical name] 8-chloro-6,11-dihydro-11- (4-piperidine subunit) -5H-benzo- [5,6] cycloheptane [1,2-b] pyridine

[In vivo process] Oral absorption is good, peak plasma concentration is reached in about 3 hours, and elimination half-life is about 27 hours. Evidence shows that continuous administration will not produce clinically relevant drug accumulation in the body, no food was found to desloratadine Effect on metabolism.

[Pharmacological mechanism]

Cetirizine

[Trade name] Vircox, Cetrizet,

Azelastine

[Product name] Azeptin ASTELIN

[Synonym] Azelastine hydrochloride

[Chemical name] (±) -4- (4-chlorobenzyl) -2- (hexahydro-1-methyl-1H-azapyridyl-4) 1 (2H) phthalazinone hydrochloride

[Properties] White crystalline powder, odorless, bitter taste, easily soluble in chloroform, dichloromethane and glacial acetic acid, slightly soluble in methanol, slightly soluble in water or absolute ethanol, insoluble in acetone and ether. Melting point is 225-229 ° C.

[In vivo process] After taking azelastine 1mg, 2mg, 3mg and 4mg respectively, the peak plasma concentration was reached in 3-4 hours, and the peak concentrations were 0.6ng / ml, 1.1ng / ml, 2.0ng / ml and 12 respectively. 7ng / ml. Twice daily, 3mg each time for 3-4 consecutive days can stabilize the plasma concentration at 3-4ng / ml; peak plasma concentration time is 4 hours when 1-3mg orally, and 5 hours when 4mg orally. The biological half-life of azelastine is about 16-25 hours. After oral administration, liver metabolism is the main factor, and bioavailability is 78%. Adult healthy people take 10mg orally at one time, and only 2.5% are excreted from the urine in the original form within 72 hours, and 1.2% are excreted from the feces. Excretion is 25%, and excretion is 53.2%. Demethyl azelastine hydrochloride is the active ingredient in the metabolite, and its half-life is about 42 hours.

[Pharmacological mechanism] Since the discovery of azelastine in Japan in 1981, many laboratories have conducted extensive basic and clinical pharmacological studies on it, but so far its pharmacological mechanism has not been fully elucidated. Azelastine is derived from phthalazine, its molecular formula is C22H24 CIN3O.HCI, and its molecular weight is 418.37. Aztrostine is a chemical structure that mimics ketotifen, and has been structurally modified, so it is not only similar in structure to ketotifen, but also very close in pharmacological mechanism and clinical effects. It was initially thought to have only H1 receptor antagonistic effects, so it was classified as an antihistamine antiallergic drug, but further research confirmed that in addition to histamine antagonistic effects, azelastine has multiple antiallergic mechanisms and is considered to be It is a new kind of asthma treatment with strong effect, long time duration, anti-airway inflammation properties, and improved allergic rhinitis symptoms. Aztrostine's extensive pharmacological effects and good clinical efficacy have attracted the attention of clinicians and have been widely used in Europe and the United States. At present, it is believed that the mechanism of azelastine in the treatment of asthma has at least the following aspects:

1. Directly block the binding of histamine to the H1 receptor: Azelastine has the pharmacological activity of selectively binding to the H1 receptor. Its binding effect on the H1 receptor is the strongest among all antihistamine drugs. Its binding to the H1 receptor is a non-competitive form of binding, which is not easily replaced by local high concentrations of histamine.

2. Inhibit the release of histamine and leukotriene by mast cells: Azelastine can enhance the membrane stability of mast cells and inhibit the release of inflammatory mediators such as histamine and leukotriene by mast cells. It inhibits antigen and non-antigen stimulation Histamine release by mast cells is 5000 times stronger than ketotifen, sodium cromoglycate, theophylline, and astemizole. The mechanism is that azelastine can inhibit the activity of 5-lipoxygenase in the cell, block the inflow of calcium ions, increase the level of cAMP and stabilize the mast cell membrane. Animal experiments show that azelastine can significantly inhibit the activity of histamine, leukotriene and other inflammatory mediators released by mast cells / basophils in guinea pigs, rats and rabbits. Azelastine is selectively absorbed by alveolar macrophages in the lungs and airways, and inhibits their release of cytokines and leukotrienes. Azelastine also significantly inhibited the release activity of human mast cells induced by the allergen, A23187 and 48 \ 80 complexes, but had no effect on the spontaneous release of mast cells; when the concentration of Azelastine was At 1-30umol \ L, it can inhibit the release of leukotriene by mast cells, and the intensity of the effect is dose-dependent.

3. Antagonizing other inflammatory mediators: Animal experiments have shown that azelastine can significantly inhibit the experimental asthma induced by thiopeptide leukotriene in guinea pigs. Clinical studies have shown that azelastine can significantly inhibit bronchial smooth muscle spasm activity induced by human inhalation of thiopeptide leukotriene. In addition, animal tests have confirmed that azatrostin can antagonize inflammatory mediators such as bradykinin, substance P, serotonin, and platelet activating factor. Among them, the effect of antagonizing leukotriene is stronger.

4. Inhibition of the number and release activity of airway inflammatory cells: Animal experiments have confirmed that azelastine can significantly reduce the increase in the number of eosinophils induced by asthma guinea pig allergen inhalation challenge test. Studies have also confirmed that azelastine can also inhibit the ability of macrophages to synthesize interleukin-1 and TNF- in mice. In recent years, it has been found that azelastine can inhibit the synthesis and release of thiopeptide leukotriene by human eosinophils, neutrophils and macrophages, and also inhibit the ability of eosinophils to synthesize PAF.

5. Inhibit phosphodiesterase activity and increase cAMP concentration in cells:

6. Enhance the sensitivity of 2 adrenergic receptors in the airways and reverse the low regulation of 2 adrenergic receptors caused by long-term use of 2 receptor agonists.

In addition to the above pharmacological effects, azelastine can also inhibit the release of acetylcholine from the vagus nerve and prevent the influx of calcium from target cells. Long-term use can reduce airway hyperresponsiveness.

Clinical application

Aztrostine was first introduced by the German company Asta-werk in 1986. It is an antihistamine antiallergic drug that is effective for oral inhalation and can prevent and treat asthma. It has a strong airway anti-inflammatory effect. Now it has been marketed in more than 10 countries including Europe and the United States. In 1997, Aztrostine aerosol was approved by the US FDA. From the current state of research, azelastine is a promising new drug for the treatment of asthma with anti-inflammatory properties. Clinical studies have shown that a single oral azelastine 8.8mg can relieve bronchospasm for 6-8 hours, and its bronchial spasmolytic effect is close to that of inhaled 2-receptor agonists, which is stronger than theophylline slow-release agents. Oral azelastine 8mg before the allergen bronchial challenge test can bi-directionally inhibit the rapid-phase and late-phase asthma responses. 4mg twice daily for two weeks can significantly improve asthma in adults and adolescents. In terms of improving pulmonary ventilation indicators, oral azelastine 8 mg twice daily was similar to the oral theophylline sustained-release tablet 700 mg / day or ketotifen 20 mg / day. Low-dose azelastine has also achieved good results in the prevention and treatment of mild to moderate asthma. In an observation of 54 patients with asthma, it was confirmed that 4 mg of azelastine was taken orally daily, and 52% of patients took two weeks of continuous administration. Symptoms improved significantly after 74 and 81% of patients improved their lung function after four and six weeks, respectively. Recently, the results of an international joint research group on azelastine concluded that azelastine was significantly better than placebo in alleviating asthma symptoms.

In several observations on the efficacy of pediatric asthma, it has been confirmed that children with asthma aged 3-5 years 2 times a day, 1 mg each time. The clinical symptoms of children with mild to moderate asthma during medication can be completely controlled; children with moderate to severe asthma Can significantly reduce the number of asthma attacks and reduce the severity of attacks, pulmonary function indicators have been significantly improved; children over 5 years of age 2 times a day, 5mg each time also achieved similar efficacy, in 136 cases of 5-12 years old Children with asthma, given azatrostin 2-4mg twice daily, can achieve better efficacy than oral ketotifen 1mg twice daily.

Aztrostine can improve the symptoms of asthma, at the same time, it also has the effect of improving allergic rhinitis and atopic dermatitis, and has a certain effect on improving the atopic quality of asthma patients.

[Formulation and dosage] Aztrostine hydrochloride tablets are available in 4mg and 2mg each. The recommended clinical dose for adults and adolescents over 12 years is 4 mg twice daily; to prevent asthma attacks in the early morning at night, 8 mg can be taken before bedtime. For children 6 to 12 years old, 2 mg can be given twice daily. In addition, the drug has been made into MDI inhalation dosage forms and 0.2% granular preparations for children.

[Side effects] Aztrostine has a low incidence of side effects and is relatively minor. Asthma patients take this product orally at 4 mg / day, and the total incidence of side effects is 7-14%, while 8 mg / day is 18-25%. The side effects of oral administration are mainly drowsiness and burnout, with an incidence of 3-18%. Taste abnormalities are also common with an incidence of 2-26%. Other adverse reactions are rare, including occasional dry mouth, nausea, Poor appetite, abdominal pain, diarrhea, numbness of hands and feet, weight gain, facial fever, drug rash, and increased liver enzyme activity, the incidence rates are all below 5%. Side effects were significantly reduced when administered by inhalation. Volunteer oral high-dose azelastine studies have shown that there is no interaction between this product and erythromycin, ketoconazole, ranitidine, and theophylline; testing for patients taking erythromycin or ketoconazole No conductive system affecting the heart was found.

Precautions

1. Animal experiments have confirmed that high-dose azelastine has teratogenic effects, so women in pregnancy and lactation should use this product with caution. FDA classifies azelastine as Class C (less safe) for pregnant women;

2. There are no data on the safety of newborns and infants.

3. Due to drowsiness side effects, dangerous mechanical operators such as drivers should be disabled or used with caution.

4. Alcohol can enhance the central inhibitory effect of azelastine, so you should not drink alcohol during medication.