What drugs are used for chronic cough? How to use it? A complete summary of the article

Severe chronic cough can have a serious impact on the patient's work and life, so what drugs can treat chronic cough? Let's move on!

1. Common causes

Common causes such as cough variant asthma (CVA), upper airway cough syndrome (UACS), eosinophilic bronchitis (EB), allergic cough (AC), and gastroesophageal reflux cough (GERC), which account for 70% to 95% of chronic cough causes, should be considered first in the diagnosis of chronic cough. Second, chronic bronchitis, occupational cough, angiotensin-converting enzyme inhibitors (ACE Inhibitors), and other drug-induced coughs are also common causes [1].

The cause is different, and the treatment drug selected is also different, so the diagnosis and treatment of chronic cough must pay attention to the history and the search for the cause.

2. Treatment of etiology

Etiological treatment drugs include glucocorticoids, beta2-agonists, antihistamines, anti-reflux drugs, and antibiotics.

(1) Glucocorticoids:

Glucocorticoids can interfere with arachidonic acid metabolism, reduce the synthesis of leukotrienes and prostaglandins, inhibit the synthesis of cytokines, reduce microvascular leakage, increase the synthesis of β2 receptors on the cell membrane, thereby reducing airway epithelial inflammation and reducing airway hyperreactivity, for the treatment of CVA, EB, UACS and AC.

Inhaled corticosteroids (ICS) are currently the first choice for the long-term standardized treatment of CVA and EB, representing drugs such as budesonide, beclomethasone, fluticasone and so on. EB responds well to glucocorticoids, the cough disappears quickly or decreases significantly after treatment, and it is recommended to continue to use for more than 8 weeks.

Initial treatment can be combined with oral prednisone 10 to 20 mg/day for 3 to 5 days. If ineffective, attention should be paid to the presence of systemic disorders associated with eosinophilia, such as eosinophilic hypertrophic syndrome and eosinophilic granulomatous polyangiitis [1].

Inhaled ICS plus bronchodilators such as long-acting beta2 agonists or ICS alone are recommended in patients with CVA. Combination therapy provides faster and more effective relief of cough symptoms than ICS or bronchodilator alone, with a duration of at least 6 to 8 weeks. Most patients with CVA respond very well to treatment, but some patients relapse after discontinuation of the drug, and even develop in the direction of typical asthma, requiring long-term prophylaxis. UACS, a disease based on allergic rhinitis, is currently the preferred nasal inhalation of glucocorticoids, commonly used as budesonide, and the duration of treatment ≥ 12 weeks [2].

(2) β2 receptor agonists

β2 receptor agonists can excite β2 receptors on the surface of the airway smooth muscle and mast cell membrane, relax the smooth muscle of the airway, reduce the release of mast cell and basophil degranulation and its mediators, reduce the permeability of microvessels, increase the oscillation of the airway epithelial cilia. Representative drugs are salmeterol, formoterol, bambouterol and the like. The first two are often combined with glucocorticoids to make a dry powder for the treatment of cough variant asthma. Bambutrol is administered orally every night before bedtime, and the effect is long and the effect can last for 24 hours.

(3) Antihistamines

The first generation of antihistamines has a short half-life, easy to pass through the blood-brain barrier, can block cholinergic receptors, has a central antitussive and anticholinergic effect, but is easy to cause adverse reactions such as sedative drowsiness, representing drugs such as chlorpheniramine maleate and ketotefen.

Despite the above adverse reactions, first-generation antihistamines still have an irreplaceable advantage over second-generation antihistamines in the treatment of UACS caused by non-allergic rhinitis. Compared with the first generation of antihistamines, the second generation of antihistamines has a prolonged half-life, is difficult to pass through the blood-brain barrier, acts specifically on peripheral H1 histamine receptors, and does not cause adverse reactions such as sedation and drowsiness, representing the drugs such as loratadine and cetirizine [2].

Non-allergic rhinitis and the common cold: oral first-generation antihistamines and decongestants are currently the first choice. Most patients respond within a few days to 2 weeks after initial treatment. Allergic rhinitis: currently the preferred treatment with nasal inhaled nasal glucocorticoids and oral second-generation antihistamines is recommended[1]. AC therapy recommends inhaled ICS and/or oral antihistamine therapy for more than 4 weeks, with short-term oral low-dose glucocorticoids for 3 to 5 days.

(4) Anti-reflux drugs

Antirelux drugs include acid suppressants, gastric motility agents, and gastric mucosal protectors. In the treatment of gastroesophageal reflux cough (GERC), the drug is often combined, and some patients are effective with acid suppressants alone. If H2 receptor blockers are ineffective, switching to proton pump inhibitors (PPIs) may be effective.

PPI alone or in combination with gastric motility medication for 6 weeks can provide 80% gerclepsy. The onset time of drug therapy is slow, generally taking 2 to 4 weeks to take effect, and generally need to continue treatment for 3 months after the cough disappears, and then gradually stop the drug.

1. H2 receptor blocker: the drug inhibits the secretion of basal gastric acid and nocturnal gastric acid by blocking the H2 receptor on parietal cells, and its inhibition of gastric acid secretion is stronger and longer-lasting than that of anticholinergic drugs, and sudden discontinuation of the drug will lead to an increase in gastric acid secretion rebound. Commonly used H2 receptor blockers include famotidine, ranitidine, cimetidine and so on. The intensity of action of famotidine is 30 to 100 times greater than that of cimetidine, 6 to 10 times greater than that of ranitidine, and the time of action is about 30% longer than that of cimetidine and ranitidine.

2. Proton pump inhibitors: PPI is a kind of gastric acid secretion inhibitory drugs found to be strong, the first generation has omeprazole, lansoprazole and pantoprazole, there are obvious individual differences in pharmacokinetics and pharmacodynamics, and the acid suppression effect may be relatively large between different patients. In addition, in most cases, the first generation of PPIs can exert maximum acid-suppressing effects only after multiple administrations and cannot inhibit gastric acid for 24 hours, so clinical use is limited. The new generation of esomeprazole has a strong and long-lasting acid inhibition effect, and has a strong ability to inhibit gastric acid at night, which is time-dose dependent.

3. Gastric motility drugs: domperidone is the first peripheral dopamine receptor antagonist, with poor permeability to the blood-brain barrier and small central adverse reactions. Cisapride increases the release of acetylcholine by stimulating the 5-HT4 receptors of the intermuscular motor neurons of the enteric nervous system, exerting its total gastrointestinal provocative effect. Tosapride is a new generation of gastrointestinal motility drugs, which are more potent and selective 5-HT4 receptor agonists, enhance gastric and duodenal movements, and have no effect on the small intestine and colon.

4. Gastric mucosal protective drugs: can be used to enhance the cellular barrier and mucus-bicarbonate barrier function of the gastric mucosa, representative drugs are sucralfate and aluminum magnesium carbonate. Because the adverse reactions of sucralfate are large, it is easy to cause constipation, and it is generally only used for short periods of time. Aluminum magnesium carbonate only acts on the gastrointestinal tract, adverse reactions are small, its active ingredient hydrated magnesium hydroxide aluminum has a special layered network structure, which has an important cytoprotective effect on the gastric mucosal barrier.

(5) Antibiotics

Most chronic coughs are not associated with infection and do not require antimicrobial treatment. However, UACS caused by bacterial sinusitis is mostly a mixed infection, and anti-infection is an important measure, and antibiotics should be actively selected according to the common pathogenic bacteria and drug sensitivity of the patient's location. Common pathogens of bacterial sinusitis are Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis, and commonly used drugs include amoxicillin/clavulanate, cephalosporins, or quinolones.

When recurrent prolongation or severe sinusitis occurs, the pathogenic bacteria may be considered anaerobic, and can be treated with clindamycin, metronidazole, and other broad-spectrum antibiotics. Antibiotic treatment for acute bacterial sinusitis ≥ 2 weeks, and prolonged use is recommended as appropriate for chronic disease [2].

3. Symptomatic treatment

The symptomatic treatment of cough can first be divided into antitussive therapy and expectorant therapy according to the mechanism of action. Antitussive therapy is divided into central antitussive and peripheral antitussive therapy.

(1) Central antitussive drugs: This type of drug has an inhibitory effect on the bulbar center. According to whether it has addictive and anesthetic effects, it can be divided into dependent and non-dependent antitussive drugs. The former is a morphine alkaloid and its derivatives, which have a very obvious antitussive effect, but also have analgesic and sedative effects, and can be used for severe dry cough and irritating cough caused by various causes, especially cough accompanied by chest pain, representing the drugs codeine and forcodine [2].

Due to its addictive nature, it is only used briefly when other treatments are ineffective. Non-dependent cough suppressants are mostly synthetic antitussive drugs, representative drugs are dextromethorphan and pentovirin, the more widely used clinical application is dextromethorphan, its effect is similar to codeine, but there is no analgesic and hypnotic effect, the therapeutic dose has no inhibitory effect on the respiratory center, and there is no addiction.

(2) Peripheral cough suppressants: also known as peripheral cough suppressants, which play an antitussive role by inhibiting receptors, afferent nerves and effectors in the cough reflex arc. Such drugs include local anesthetics and mucosal protective drugs, representing the drugs nacotin, bermiperin, mogisteine and so on.

Fourth, expectorants

Expectorant therapy improves cough efficiency in clearing airway secretions. The mechanism of action of expectorant drugs includes: increasing the discharge of secretions, reducing the viscosity of secretions, and enhancing the clearance function of cilia.

(1) Guaiacol glycerol ether, which can stimulate the gastric mucosa, reflexively causes an increase in airway secretions, reduces the viscosity of sputum, and has a certain bronchodilation effect to achieve the effect of enhancing mucus discharge. It is often used in combination with antihistamines, antitussive drugs, and decongestants.

(2) The main components of myrtle oil include eucalyptin, limonene and α-pinene, which can promote the movement of cilia of the airway and sinus mucosa, and can be used for acute bronchitis, chronic bronchitis and sinusitis and other diseases.

(3) Ambroxol and bromohexine: both belong to mucolytic agents, and ambroxol is bromoxanin in the body

Metabolites, which destroy the acidic mucopolysaccharide structure of the mucinoids, reduce the viscosity of secretions, promote ciliary movement and enhance the concentration of antibacterial drugs in the respiratory tract. For use in patients with symptoms of sputum production.

(4) Acetylcysteine: it can break the sulfur bond of the mucus glycoprotein polypeptide chain, reduce the viscosity of sputum, and at the same time have antioxidant effects, which is used for chronic cough patients with high mucus secretion of sputum.

(5) Carboxylsteine: it can break the disulfide bond of mucin and reduce the viscosity of secretions. Erdosteine is its precursor drug, which is metabolized orally to produce 3 metabolites containing free thiol groups and exert pharmacological effects.

Caption image source 123RF

Resources:

Asthma Group, Respiratory Disease Branch of Chinese Medical Association. Guidelines for the diagnosis and treatment of cough (2021)[J]. Chinese Journal of Tuberculosis and Respiratory Diseases,2022,01:13-46.

Han Dejun. Analysis of common clinical causes of chronic cough and drug therapy[J]. Shenzhen Journal of Integrative Traditional and Western Medicine,2015,02:106-107.

This article is reproduced from the "Respiratory Channel of the Medical Profession"

Audit expert: Sun Danxiong, Department of Respiratory Medicine, First People's Hospital of Yunnan Province

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