Drugs for Cough

DRUGS FOR COUGH

Cough is a protective reflex, its purpose being expulsion of respiratory secretions or foreign particless from air passages. It occurs due to stimulation of mechano or chemoreceptors in throat, respiratory passages or stretch receptors in the lungs. Cough may be useful or useless. Useless (nonproductive) cough should be suppressed. Useful (productive) cough serves to drain the airway, its suppression is not desirable, may even be harmful, except if the amount of expectoration achieved is small compared to the effort of continuous coughing. Apart from specific remedies (antibiotics, etc. see box), cough may be treated as a symptom (nonspecific therapy) with:

1. Pharyngeal Demulcents

    Lozenges, cough drops, linctuses containing syrup, glycerine, liquorice.

2. Expectorants (Mucokinetics)

a.     Bronchial secretion enhancers

Sodium or Potassium citrate, Potassium iodide, Guaiphenesin (Glyceryl guaiacolate), balsum of Tolu, Vasaka, Ammonium chloride.

b.     Mucolytics

     Bromhexine, Ambroxol, Acetyl cysteine, Carbocisteine

3. Antitussives (Cough centre suppressants)

a.      Opioids  Codeine, Pholcodeine.

b.     Nonopioids Noscapine, Dextromethorphan, Chlophedianol.

c. Antihistamines Chlorpheniramine, Diphenhydramine, Promethazine.

4.   Adjuvant Antitussives

Bronchodilators  Salbutamol, Terbutalin.

Demulcents And Expectorants

Pharyngeal demulcents sooth the throat and reduce afferent impulses from the inflamed/ irritated pharyngeal mucosa, thus provide symptomatic relief in dry cough arising from throat.

Expectorants (Mucokinetics) are drugs believed to increase bronchial secretion or reduce its viscosity, facilitating its removal by coughing.

Sodium and potassium citrate are considered to increase bronchial secretion by salt action. Potassium iodide is secreted by bronchial glands and can irritate the airway mucosa. Prolonged use can affect thyroid function and produce iodism. It is rarely used now. Guaiphenesin, vasaka, tolu balsum are plant products which are supposed to enhance bronchial secretion and mucociliary function while being secreted by tracheobronchial glands. Ammonium salts are nauseating—reflexly increase respiratory secretions. A variety of expectorant formulations containing an assortment of the above ingredients, often in combination with antitussives/antihistaminics are marketed and briskly promoted, but objective evidence of efficacy of these is nonconclusive.

Mucolytics

Bromhexine

A derivative of the alkaloid vasicine obtained from Adhatoda vasica (Vasaka), is a potent mucolytic and mucokinetic, capable of inducing thin copious bronchial secretion. It depolymerises mucopolysaccharides directly as well as by liberating lysosomal enzymes— network of fibres in tenacious sputum is broken. It is particularly useful if mucus plugs are present. Side effects are rhinorrhoea and lacrimation, gastric irritation, hypersensitivity.

Dose: adults 8 mg TDS, children 1–5 years 4 mg BD, 5–10 years 4 mg TDS.

BROMHEXINE 8 mg tablet, 4 mg/5 ml elixir.

Ambroxol A metabolite of bromhexine having similar mucolytic action, uses and side effects.

Dose: 15–30 mg TDS.

AMBRIL, AMBROLITE, AMBRODIL, MUCOLITE 30 mg tab, 30 mg/5 ml liquid, 7.5 mg/ml drops.

Acetylcysteine It opens disulfide bonds in mucoproteins present in sputum—makes it less viscid, but has to be administered directly into the respiratory tract.

MUCOMIX 200 mg/ml inj in 1,2,5 ml amps; injectable solution may be nebulized/instilled through trachiostomy tube.

Carbocisteine It liquefies viscid sputum in the same way as acetylcysteine and is administered orally (250–750 mg TDS). Some patients of chronic bronchitis have been shown to benefit. Side effects are g.i. irritation and rashes.

MUCODYNE 375 mg cap, 250 mg/5 ml syr.

It is available in combination with amoxicillin or cephalexin for treatment of bronchitis, bronchiectasis, sinusitis, etc.

CARBOMOX: Carbocisteine 150 mg + amoxicillin 250 or 500 mg caps. CARBICEF: Carbocisteine 150 mg + cephalexin 250 or 500 mg caps.

Antitussives

These are drugs that act in the CNS to raise the threshold of cough centre or act peripherally in the respiratory tract to reduce tussal impulses, or both these actions. Because they aim to control rather than eliminate cough, antitussives should be used only for dry unproductive cough or if cough is unduly tiring, disturbs sleep or is hazardous (hernia, piles, cardiac disease, ocular surgery).

Opioids

Codeine (see Ch. No. 34) An opium alkaloid, qualitatively similar to but less potent than morphine. It is more selective for cough centre and is treated as the standard antitussive; suppresses cough for about 6 hours. The antitussive action is blocked by naloxone indicating that it is exerted through opioid receptors in the brain. Abuse liability is low, but present; constipation is the chief draw back. At higher doses respiratory depression and drowsiness can occur—driving may be impaired. Like morphine, it is contraindicated in asthmatics and in patients with diminished respiratory reserve.

Dose: 10–30 mg; children 2–6 years 2.5–5 mg, 6–12 years 5–10 mg, frequently used as syrup codeine phos. 4–8 ml.

CODINE 15 mg tab, 15 mg/5 ml linctus.

Pholcodeine It has practically no analgesic or addicting property, but is similar in efficacy as antitussive to codeine and is longer acting—acts for 12 hours; dose: 10–15 mg. (ETHNINE 5 mg/5 ml syr).

Non-Opioids

Noscapine (Narcotine) An opium alkaloid of the benzoisoquinoline series (see Ch. No. 34). It depresses cough but has no narcotic, analgesic or dependence inducing properties. It is nearly equipotent antitussive as codeine, especially useful in spasmodic cough. Headache and nausea occur occasionally as side effect. It can release histamine and produce bronchoconstriction in asthmatics.

Dose: 15–30 mg, children 2–6 years 7.5 mg, 6–12 years 15 mg.

COSCOPIN 7 mg/5 ml syrup, COSCOTABS 25 mg tab.

Dextromethorphan A synthetic compound; the disomer has selective antitussive action (raises threshold of cough centre) while lisomer is analgesic. Dextromethorphan is as effective as codeine, does not depress mucociliary function of the airway mucosa and is practically devoid of constipating and addicting actions. The antitussive action lasts for ~ 6 hours and is not blocked by naloxone: therefore not exerted through opioid receptors.

Side effect: Dizziness, nausea, drowsiness, ataxia.

Dose: 10–20 mg, children 2–6 years 2.5–5 mg, 6–12 years 5–10 mg.

Chlophedianol It is a centrally acting antitussive with slow onset and longer duration of action. Side effect: Dryness of mouth, vertigo, irritability.

Dose: 20–40 mg; DETIGON, TUSSIGON 20 mg/5 ml linctus with Ammon. chloride 50 mg and menthol 0.25 mg.

Antihistamines

Many H₁ antihistamines have been conventionally added to antitussive/expectorant formulations (see below). They afford relief in cough due to their sedative and anticholinergic actions, but lack selectivity for the cough centre. They have no expectorant property, may even reduce secretions by anticholinergic action. They have been specially promoted for cough in respiratory allergic states, though their lack of efficacy in asthma is legendary.

Chlorpheniramine (2–5 mg), Diphenhydramine (15–25 mg) and Promethazine (15–25 mg; PHENERGAN 5 mg/5 ml elixir) are commonly used. Second generation antihistamines like fexofenadine, loratadine are ineffective.

Bronchodilators Bronchospasm can induce or aggravate cough. Stimulation of pulmonary receptors can trigger both cough and bronchoconstriction, especially in individuals with bronchial hyperreactivity. Bronchodilators relieve cough in such individuals and improve the effectiveness of cough in clearing secretions by increasing surface velocity of airflow during cough. They should be used only when an element of bronchoconstriction is present and not routinely. Their fixed dose combinations with antitussives are not satisfactory because of differences in time course of action of the components and liability for indiscriminate use.

Fixed dose combinations of a centrally acting antitussive with a bronchodilator or with an antihistaminic having high atropinic activity have been banned in India, but many are still marketed.

Aeromatic chest rub is widely advertized as a cough remedy. Though it has been shown to reduce experimentally induced cough in healthy volunteers, there is no evidence of benefit in pathological cough.